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    Clinical Trial Results:
    A Phase II, Open Label, Randomized, Two-Arm Study to Investigate the Efficacy and Safety of Two Doses of the Antibody Drug Conjugate GSK2857916 in Participants with Multiple Myeloma Who Had 3 or More Prior Lines of Treatment, Are Refractory to a Proteasome Inhibitor and an Immunomodulatory Agent and Have Failed an Anti-CD38 Antibody (DREAMM 2)

    Summary
    EudraCT number
    		 2017-004810-25
    Trial protocol
    		 GB   DE   ES   IT  
    Global end of trial date

    Results information
    Results version number
    		 v2
    This version publication date
    12 Nov 2023
    First version publication date
    26 Apr 2020
    Other versions
    		 v1 , v3
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    205678
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 GreatWest Road, Brentford,Middlesex, United Kingdom, TW8 9GS
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Interim
    Date of interim/final analysis
    04 May 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    21 Jun 2019
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the clinical efficacy of 2 doses of GSK2857916 in participants with relapsed/refractory multiple myeloma
    Protection of trial subjects
    In order to minimize corneal events associated with GSK2857916 prophylactic preservative-free artificial tears should be administered in each eye at least 4 to 8 times daily beginning on Cycle 1 Day 1 until the end of treatment. In the event of ocular symptoms (e.g., dry eyes), the use of artificial tears may be increased up to every 2 hours as needed. While not yet clinically demonstrated, it is theoretically possible that the application of a cooling eye mask during GSK2857916 administration, and in the first few hours after infusion may subsequently decrease ocular side effects. On the day of infusion at the discretion of the participant and the investigator, the following may be considered: • Beginning with the start of each GSK2857916 infusion, participants may apply cooling eye masks to their eyes for approximately 1 hour or as much as tolerated. • Participants may continue using the cooling eye mask beyond the first hour for up to 4 hours. Further use beyond 4 hours is at the participant’s discretion. Participants should receive full supportive care during the study, including transfusions of blood products, growth factors, and treatment with antibiotics, anti-emetics, antidiarrheal, and analgesics, as appropriate. Concomitant therapy with bisphosphonates is allowed. Participants may receive local irradiation for pain or stability control.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    18 Jun 2018
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety, Scientific research
    Long term follow-up duration
    		 5 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 5
    Country: Number of subjects enrolled
    Canada: 12
    Country: Number of subjects enrolled
    France: 26
    Country: Number of subjects enrolled
    Germany: 16
    Country: Number of subjects enrolled
    Italy: 7
    Country: Number of subjects enrolled
    Spain: 17
    Country: Number of subjects enrolled
    United Kingdom: 12
    Country: Number of subjects enrolled
    United States: 126
    Worldwide total number of subjects
    221
    EEA total number of subjects
    66
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    91
    From 65 to 84 years
    127
    85 years and over
    3

    Subject disposition

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    Recruitment
    Recruitment details
    		 This was an open-label, randomized, multicenter study to evaluate the efficacy and safety of belantamab mafodotin monotherapy at a dose of 2.5 milligram per kilogram (mg/kg) or 3.4 mg/kg, given intravenously (IV) in participants with relapsed/refractory multiple myeloma (RRMM).

    Pre-assignment
    Screening details
    		 A total of 221 participants were enrolled.The results presented based on data cut-off date of 04 May 2022.Those participants still benefiting from study drug in opinion of treating physician continued to receive study drug in Post Analysis Continued Treatment phase their data will be reported after they stop receiving treatment per protocol.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 GSK2857916 2.5 mg/kg (Frozen liquid)
    Arm description
    		 Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of up to 39 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK2857916
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    GSK2857916 frozen liquid was available as 30 milligrams pervial solution in single-use vial. It was diluted with 0.9 percent saline to the appropriate concentration for the dose (2.5milligram per kilogram [mg/kg]).Participants were administered GSK2857916 via intravenous route

    Arm title
    		 GSK2857916 3.4 mg/kg (Frozen liquid)
    Arm description
    		 Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of up to 32 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK2857916
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate and solvent for concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    GSK2857916 frozen liquid wasavailable as 30 milligrams pervial solution in single-use vial. Itwas diluted with 0.9 percent saline to the appropriate concentration for the dose (3.4mg/kg]. Participants were administered GSK2857916 viaintravenous route.

    Arm title
    		 GSK2857916 3.4 mg/kg (Lyophilized)
    Arm description
    		 Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of up to 35 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GSK2857916
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Intravenous use
    Dosage and administration details
    GSK2857916 lyophilized powderwas available as 100 milligramsper vial in single-use vial forreconstitution. It wasreconstituted using water for injection and diluted with 0.9percent saline to the appropriate concentration for the dose (3.4mg/kg). Participants were administered GSK2857916 viaintravenous route.

    Number of subjects in period 1
    		GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Started
    97
    99
    25
    Received Study Treatment
    95
    99
    24
    Completed
    0
    0
    0
    Not completed
    97
    99
    25
         Physician decision
    2
    4
    -
         Consent withdrawn by subject
    8
    2
    2
         other reasons
    14
    10
    5
         Death
    70
    80
    16
         ongoing at the time of analysis
    1
    2
    -
         Lost to follow-up
    2
    1
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    GSK2857916 2.5 mg/kg (Frozen liquid)
    Reporting group description
    		 Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of up to 39 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.

    Reporting group title
    GSK2857916 3.4 mg/kg (Frozen liquid)
    Reporting group description
    		 Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of up to 32 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.

    Reporting group title
    GSK2857916 3.4 mg/kg (Lyophilized)
    Reporting group description
    		 Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of up to 35 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.

    Reporting group values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized) Total
    Number of subjects
    		 97 99 25 221
    Age categorical
    Baseline characteristics were presented for all randomized participants including 3 randomized participants who never received treatment (2-withdrawal by physician decision and 1-death).
    Units: Participants
        Total Participants
    		 97 99 25 221
    Age Continuous
    Baseline characteristics were presented for all randomized participants including 3 randomized participants who never received treatment (2-withdrawal by physician decision and 1-death).
    Units: years
        arithmetic mean (standard deviation)
    		 64.1 ( 10.01 ) 66.0 ( 9.09 ) 67.2 ( 10.78 ) -
    Sex: Female, Male
    Baseline characteristics were presented for all randomized participants including 3 randomized participants who never received treatment (2-withdrawal by physician decision and 1-death).
    Units: Participants
        Female
    		 46 43 11 100
        Male
    		 51 56 14 121
    Race/Ethnicity, Customized
    Baseline characteristics were presented for all randomized participants including 3 randomized participants who never received treatment (2-withdrawal by physician decision and 1-death).
    Units: Subjects
        Black or African American
    		 16 11 3 30
        Asian - Central/South Asian Heritage
    		 1 0 0 1
        Asian - East Asian Heritage
    		 1 0 0 1
        Asian - South East Asian Heritage
    		 0 1 1 2
        White - Arabic/North African Heritage
    		 4 2 0 6
        White - White/Caucasian/European Heritage
    		 72 83 21 176
        Mixed Asian Race
    		 0 1 0 1
        Mixed White Race
    		 0 1 0 1
        Unknown
    		 1 0 0 1
        Missing
    		 2 0 0 2

    End points

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    End points reporting groups
    Reporting group title
    GSK2857916 2.5 mg/kg (Frozen liquid)
    Reporting group description
    		 Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of up to 39 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.

    Reporting group title
    GSK2857916 3.4 mg/kg (Frozen liquid)
    Reporting group description
    		 Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of up to 32 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.

    Reporting group title
    GSK2857916 3.4 mg/kg (Lyophilized)
    Reporting group description
    		 Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of up to 35 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.

    Primary: Overall response rate (ORR) by Independent Review Committee (IRC) (Full Analysis Population)

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    End point title
    		 Overall response rate (ORR) by Independent Review Committee (IRC) (Full Analysis Population) [1]
    End point description
    ORR was determined according to the 2016 international myeloma working group (IMWG) response criteria by IRC. ORR was calculated as the percentage of participants with a confirmed partial response (PR) or better (that is [i.e.], PR, very good partial response [VGPR], complete response [CR] and stringent complete response [sCR]). Confidence intervals were based on the exact method. Full Analysis Population comprised of all randomized participants (any participant who received a treatment randomization number was considered as randomized) whether or not randomized treatment was administered. This population was based on the treatment the participant was randomized to.
    End point type
    Primary
    End point timeframe
    Up to 48 weeks
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    97 [2]
    99 [3]
    25 [4]
    Units: Percentage of Participants
        number (confidence interval 97.5%)
    31 (20.8 to 42.6)
    34 (23.9 to 46.0)
    48 (25.5 to 71.1)
    Notes
    [2] - Full Analysis Population
    [3] - Full Analysis Population
    [4] - Full Analysis Population
    No statistical analyses for this end point

    Primary: Overall response rate by Independent Review Committee (Efficacy Population)

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    End point title
    		 Overall response rate by Independent Review Committee (Efficacy Population) [5] [6]
    End point description
    ORR was determined according to the 2016 IMWG response criteria by IRC. ORR was calculated as the percentage of participants with a confirmed PR or better (i.e., PR, VGPR, CR and sCR). Confidence intervals were based on the exact method. Efficacy Population comprised of first 130 intent-to-treat participants whether or not randomized treatment (frozen solution) was administered. Intent-to-treat Population comprised of all randomized participants whether or not randomized treatment was administered. Data is not presented for 'GSK2857916 3.4 mg/kg (Lyophilized)' arm as it is not included in Efficacy Population.
    End point type
    Primary
    End point timeframe
    Up to 48 weeks
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There are no statistical data to report.
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid)
    Number of subjects analysed
    64 [7]
    66 [8]
    Units: Percentage of Participants
        number (confidence interval 95%)
    30 (18.9 to 42.4)
    30 (19.6 to 42.9)
    Notes
    [7] - Efficacy Population
    [8] - Efficacy Population
    No statistical analyses for this end point

    Secondary: Overall response rate by investigator assessment (IA) (Full Analysis Population)

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    End point title
    		 Overall response rate by investigator assessment (IA) (Full Analysis Population)
    End point description
    ORR was determined by the investigator according to the 2016 IMWG response criteria. ORR was calculated as the percentage of participants with a confirmed PR or better (i.e., PR, VGPR, CR and sCR). Confidence intervals were based on the exact method. Percentage values are rounded off.
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    97 [9]
    99 [10]
    25 [11]
    Units: Percentage of Participants
        number (confidence interval 95%)
    33 (23.8 to 43.3)
    32 (23.3 to 42.5)
    52 (31.3 to 72.2)
    Notes
    [9] - Full Analysis Population
    [10] - Full Analysis Population
    [11] - Full Analysis Population
    No statistical analyses for this end point

    Secondary: Clinical benefit rate (CBR) by investigator assessment (Full Analysis Population)

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    End point title
    		 Clinical benefit rate (CBR) by investigator assessment (Full Analysis Population)
    End point description
    CBR was determined by the investigator according to the 2016 IMWG response criteria. CBR was calculated as the percentage of participants with a confirmed minimal response (MR) or better (i.e., MR, PR, VGPR, CR and sCR). Confidence intervals were based on the exact method. Percentage values are rounded off.
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    97 [12]
    99 [13]
    25 [14]
    Units: Percentage of Participants
        number (confidence interval 95%)
    35 (25.6 to 45.4)
    38 (28.8 to 48.7)
    60 (38.7 to 78.9)
    Notes
    [12] - Full Analysis Population
    [13] - Full Analysis Population
    [14] - Full Analysis Population
    No statistical analyses for this end point

    Secondary: Overall response rate by investigator assessment (Efficacy Population)

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    End point title
    		 Overall response rate by investigator assessment (Efficacy Population) [15]
    End point description
    ORR was determined by the investigator according to the 2016 IMWG response criteria. ORR was calculated as the percentage of participants with a confirmed PR or better (i.e., PR, VGPR, CR and sCR). Confidence intervals were based on the exact method. Data is not presented for 'GSK2857916 3.4 mg/kg (Lyophilized)' arm as it is not included in Efficacy Population. Percentage values are rounded off.
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There are no statistical data to report.
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid)
    Number of subjects analysed
    64 [16]
    66 [17]
    Units: Percentage of Participants
        number (confidence interval 95%)
    33 (21.6 to 45.7)
    26 (15.8 to 38.0)
    Notes
    [16] - Efficacy Population.
    [17] - Efficacy Population.
    No statistical analyses for this end point

    Secondary: Clinical benefit rate by investigator assessment (Efficacy Population)

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    End point title
    		 Clinical benefit rate by investigator assessment (Efficacy Population) [18]
    End point description
    CBR was determined by the investigator according to the 2016 IMWG response criteria. CBR was calculated as the percentage of participants with a confirmed MR or better (i.e., MR, PR, VGPR, CR and sCR). Confidence intervals were based on the exact method. Data is not presented for 'GSK2857916 3.4 mg/kg (Lyophilized)' arm as it is not included in Efficacy Population. Percentage values are rounded off.
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There are no statistical data to report.
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid)
    Number of subjects analysed
    64 [19]
    66 [20]
    Units: Percentage of Participants
        number (confidence interval 95%)
    34 (22.9 to 47.3)
    35 (23.5 to 47.6)
    Notes
    [19] - Efficacy Population.
    [20] - Efficacy Population.
    No statistical analyses for this end point

    Secondary: Clinical benefit rate by Independent Review Committee (Full Analysis Population)

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    End point title
    		 Clinical benefit rate by Independent Review Committee (Full Analysis Population)
    End point description
    CBR was determined according to the 2016 IMWG response criteria by IRC. CBR was calculated as the percentage of participants with a confirmed MR or better (i.e., MR, PR, VGPR, CR and sCR). Confidence intervals were based on the exact method. Percentage values are rounded off.
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    97 [21]
    99 [22]
    25 [23]
    Units: Percentage of Participants
        number (confidence interval 95%)
    36 (26.6 to 46.5)
    40 (30.7 to 50.7)
    56 (34.9 to 75.6)
    Notes
    [21] - Full Analysis Population
    [22] - Full Analysis Population
    [23] - Full Analysis Population
    No statistical analyses for this end point

    Secondary: Clinical benefit rate by Independent Review Committee (Efficacy Population)

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    End point title
    		 Clinical benefit rate by Independent Review Committee (Efficacy Population) [24]
    End point description
    CBR was determined according to the 2016 IMWG response criteria by IRC. CBR was calculated as the percentage of participants with a confirmed MR or better (i.e., MR, PR, VGPR, CR and sCR). Confidence intervals were based on the exact method. Data is not presented for 'GSK2857916 3.4 mg/kg (Lyophilized)' arm as it is not included in Efficacy Population. Percentage values are rounded off.
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There are no statistical data to report.
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid)
    Number of subjects analysed
    64 [25]
    66 [26]
    Units: Percentage of Participants
        number (confidence interval 95%)
    34 (22.9 to 47.3)
    38 (26.2 to 50.7)
    Notes
    [25] - Efficacy Population.
    [26] - Efficacy Population.
    No statistical analyses for this end point

    Secondary: Duration of response (DoR) by investigator assessment (Full Analysis Population)

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    End point title
    		 Duration of response (DoR) by investigator assessment (Full Analysis Population)
    End point description
    DoR is defined as the time from first documented evidence of PR or better until the earliest date of documented disease progression (PD) per IMWG response criteria; or death due to PD among participants who achieved an overall response, i.e., confirmed PR or better. DOR based on responses assessed by investigator is presented. Median and inter-quartile range (first quartile and third quartile) of DOR are presented. Only responders (confirmed PR or better) by investigator assessment were included in this analysis.
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    32 [27]
    32 [28]
    13 [29]
    Units: Months
        median (inter-quartile range (Q1-Q3))
    12.4 (4.2 to 21.4)
    12.6 (5.6 to 22.8)
    5.3 (2.8 to 9.0)
    Notes
    [27] - Full Analysis Population.
    [28] - Full Analysis Population.
    [29] - Full Analysis Population.
    No statistical analyses for this end point

    Secondary: Duration of response by Independent Review Committee (Full Analysis Population)

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    End point title
    		 Duration of response by Independent Review Committee (Full Analysis Population)
    End point description
    DoR is defined as the time from first documented evidence of PR or better until the earliest date of documented PD per IMWG response criteria; or death due to PD among participants who achieved an overall response, i.e., confirmed PR or better. DOR based on responses assessed by IRC is presented. Median and inter-quartile range (first quartile and third quartile) of DOR are presented. Only responders (confirmed PR or better) by Independent Review committee were included in this analysis.88888 indicates <75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived.
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    31 [30]
    35 [31]
    13 [32]
    Units: Months
        median (inter-quartile range (Q1-Q3))
    12.5 (4.2 to 19.4)
    6.2 (4.2 to 88888)
    9.0 (3.4 to 10.4)
    Notes
    [30] - Full Analysis Population.
    [31] - Full Analysis Population.
    [32] - Full Analysis Population.
    No statistical analyses for this end point

    Secondary: Duration of response by investigator assessment (Efficacy Population)

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    End point title
    		 Duration of response by investigator assessment (Efficacy Population) [33]
    End point description
    DoR is defined as the time from first documented evidence of PR or better until the earliest date of documented PD per IMWG response criteria; or death due to PD among participants who achieved an overall response, i.e., confirmed PR or better. DOR based on responses assessed by investigator is presented. Median and inter-quartile range (first quartile and third quartile) of DOR are presented. Data is not presented for 'GSK2857916 3.4 mg/kg (Lyophilized)' arm as it is not included in Efficacy Population. Only responders (confirmed PR or better) by investigator assessment were included in this analysis. 88888 indicates <75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    Notes
    [33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There are no statistical data to report.
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid)
    Number of subjects analysed
    21 [34]
    17 [35]
    Units: Months
        median (inter-quartile range (Q1-Q3))
    6.9 (4.2 to 20.8)
    15.9 (12.6 to 88888)
    Notes
    [34] - Efficacy Population.
    [35] - Efficacy Population.
    No statistical analyses for this end point

    Secondary: Duration of response by Independent Review Committee (Efficacy Population)

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    End point title
    		 Duration of response by Independent Review Committee (Efficacy Population) [36]
    End point description
    DoR is defined as the time from first documented evidence of PR or better until the earliest date of documented PD per IMWG response criteria; or death due to PD among participants who achieved an overall response, i.e., confirmed PR or better. DOR based on responses assessed by IRC is presented. Median and inter-quartile range (first quartile and third quartile) of DOR are presented. Data is not presented for 'GSK2857916 3.4 mg/kg (Lyophilized)' arm as it is not included in Efficacy Population. Only responders (confirmed PR or better) by Independent Review Committee were included in this analysis. 88888 indicates <75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    Notes
    [36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There are no statistical data to report.
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid)
    Number of subjects analysed
    20 [37]
    20 [38]
    Units: Months
        median (inter-quartile range (Q1-Q3))
    11.0 (4.0 to 19.4)
    15.9 (4.2 to 88888)
    Notes
    [37] - Efficacy Population.
    [38] - Efficacy Population.
    No statistical analyses for this end point

    Secondary: Time to response by investigator assessment (Full Analysis Population)

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    End point title
    		 Time to response by investigator assessment (Full Analysis Population)
    End point description
    Time to response is defined as the time between the date of randomization and the first documented evidence of response (PR or better), among participants who achieve a response (i.e., confirmed PR or better). Time to response based on responses assessed by investigator is presented. Median and inter-quartile range (first quartile and third quartile) of time to response are presented. Only responders (confirmed PR or better) by investigator assessment were included in this analysis
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    32 [39]
    32 [40]
    13 [41]
    Units: Months
        median (inter-quartile range (Q1-Q3))
    1.5 (0.8 to 2.5)
    1.5 (0.9 to 3.0)
    0.9 (0.8 to 1.0)
    Notes
    [39] - Full Analysis Population.
    [40] - Full Analysis Population.
    [41] - Full Analysis Population.
    No statistical analyses for this end point

    Secondary: Time to response by investigator assessment (Efficacy Population)

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    End point title
    		 Time to response by investigator assessment (Efficacy Population) [42]
    End point description
    Time to response is defined as the time between the date of randomization and the first documented evidence of response (PR or better), among participants who achieve a response (i.e., confirmed PR or better). Time to response based on responses assessed by investigator is presented. Median and inter-quartile range (first quartile and third quartile) of time to response are presented. Data is not presented for 'GSK2857916 3.4 mg/kg (Lyophilized)' arm as it is not included in Efficacy Population. Only responders (confirmed PR or better) by investigator assessment were included in this analysis.
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    Notes
    [42] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There are no statistical data to report.
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid)
    Number of subjects analysed
    21 [43]
    17 [44]
    Units: Months
        median (inter-quartile range (Q1-Q3))
    1.4 (0.8 to 2.8)
    1.5 (1.4 to 2.8)
    Notes
    [43] - Efficacy Population
    [44] - Efficacy Population
    No statistical analyses for this end point

    Secondary: Time to response by Independent Review Committee (Full Analysis Population)

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    End point title
    		 Time to response by Independent Review Committee (Full Analysis Population)
    End point description
    Time to response is defined as the time between the date of randomization and the first documented evidence of response (PR or better), among participants who achieve a response (i.e., confirmed PR or better). Time to response based on responses assessed by IRC is presented. Median and inter-quartile range (first quartile and third quartile) of time to response are presented. Only responders (confirmed PR or better) by Independent Review Committee were included in this analysis
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    31 [45]
    35 [46]
    13 [47]
    Units: Months
        median (inter-quartile range (Q1-Q3))
    1.5 (0.8 to 2.2)
    1.4 (0.8 to 2.8)
    0.9 (0.8 to 2.3)
    Notes
    [45] - Full Analysis Population.
    [46] - Full Analysis Population.
    [47] - Full Analysis Population.
    No statistical analyses for this end point

    Secondary: Time to response by Independent Review Committee (Efficacy Population)

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    End point title
    		 Time to response by Independent Review Committee (Efficacy Population) [48]
    End point description
    Time to response is defined as the time between the date of randomization and the first documented evidence of response (PR or better), among participants who achieve a response (i.e., confirmed PR or better). Time to response based on responses assessed by IRC is presented. Median and inter-quartile range (first quartile and third quartile) of time to response are presented. Data is not presented for 'GSK2857916 3.4 mg/kg (Lyophilized)' arm as it is not included in Efficacy Population. Only responders (confirmed PR or better) by Independent Review Committee were included in this analysis
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    Notes
    [48] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There are no statistical data to report.
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid)
    Number of subjects analysed
    20 [49]
    20 [50]
    Units: Months
        median (inter-quartile range (Q1-Q3))
    1.5 (0.8 to 2.5)
    1.4 (1.1 to 1.9)
    Notes
    [49] - Efficacy Population.
    [50] - Efficacy Population.
    No statistical analyses for this end point

    Secondary: Progression free survival by investigator assessment

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    End point title
    		 Progression free survival by investigator assessment
    End point description
    Progression free survival is defined as the time from randomization until the earliest date of documented PD per IMWG, or death due to any cause. Progressive Disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. Progression free survival based on responses assessed by investigator is presented. Median and inter-quartile range (first quartile and third quartile) of progression free survival are presented.
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    97 [51]
    99 [52]
    25 [53]
    Units: Months
        median (inter-quartile range (Q1-Q3))
    2.2 (0.8 to 7.7)
    3.2 (1.0 to 9.8)
    3.6 (1.5 to 8.7)
    Notes
    [51] - Full Analysis Population
    [52] - Full Analysis Population
    [53] - Full Analysis Population
    No statistical analyses for this end point

    Secondary: Time to progression by investigator assessment

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    End point title
    		 Time to progression by investigator assessment
    End point description
    Time to progression is defined as the time from randomization until the earliest date of documented PD per IMWG, or death due to PD. Time to Progression based on responses assessed by investigator is presented. Median and inter-quartile range (first quartile and third quartile) of time to progression are presented.
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    97 [54]
    99 [55]
    25 [56]
    Units: Months
        median (inter-quartile range (Q1-Q3))
    2.2 (0.8 to 7.7)
    3.9 (1.0 to 11.9)
    3.6 (1.5 to 9.7)
    Notes
    [54] - Full Analysis Population
    [55] - Full Analysis Population
    [56] - Full Analysis Population
    No statistical analyses for this end point

    Secondary: Progression free survival by Independent Review Committee

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    End point title
    		 Progression free survival by Independent Review Committee
    End point description
    Progression free survival is defined as the time from randomization until the earliest date of documented PD per IMWG, or death due to any cause. Progressive Disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study. Progression free survival based on responses assessed by IRC is presented. Median and inter-quartile range (first quartile and third quartile) of progression free survival are presented.
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    97 [57]
    99 [58]
    25 [59]
    Units: Months
        median (inter-quartile range (Q1-Q3))
    2.8 (0.9 to 9.7)
    3.9 (0.8 to 9.0)
    5.7 (2.2 to 9.7)
    Notes
    [57] - Full Analysis Population
    [58] - Full Analysis Population
    [59] - Full Analysis Population
    No statistical analyses for this end point

    Secondary: Time to progression by Independent Review Committee

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    End point title
    		 Time to progression by Independent Review Committee
    End point description
    Time to progression is defined as the time from randomization until the earliest date of documented PD per IMWG, or death due to PD. Time to Progression based on responses assessed by IRC is presented. Median and inter-quartile range (first quartile and third quartile) of time to progression are presented.
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    97 [60]
    99 [61]
    25 [62]
    Units: Months
        median (inter-quartile range (Q1-Q3))
    2.9 (0.9 to 9.7)
    4.9 (0.8 to 11.1)
    5.7 (2.2 to 9.7)
    Notes
    [60] - Full Analysis Population
    [61] - Full Analysis Population
    [62] - Full Analysis Population
    No statistical analyses for this end point

    Secondary: Overall survival

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    End point title
    		 Overall survival
    End point description
    Overall survival is defined as the time from randomization until death due to any cause. Overall survival was analyzed using the Kaplan-Meier method by dose level. Median and inter-quartile range (first quartile and third quartile) of overall survival are presented. 88888 indicates <75% of participants experienced the event within the treatment arm. Hence, third-quartile could not be derived
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    97 [63]
    99 [64]
    25 [65]
    Units: Months
        median (inter-quartile range (Q1-Q3))
    15.3 (4.8 to 36.4)
    14.0 (6.2 to 26.6)
    24.5 (7.7 to 88888)
    Notes
    [63] - Full Analysis Population
    [64] - Full Analysis Population
    [65] - Full Analysis Population
    No statistical analyses for this end point

    Secondary: Number of participants with change from Baseline in hematology parameters with respect to the normal range

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    End point title
    		 Number of participants with change from Baseline in hematology parameters with respect to the normal range
    End point description
    Blood samples were collected for assessment of basophils,eosinophils,hematocrit,mean corpuscular hemoglobin (MCH),MCH concentration(MCHC),MC volume(MCV),monocyte,erythrocytes, reticulocytes.Baseline is latest pre-dose assessment(Day1)with non-missing value, including unscheduled visits.If values were unchanged(eg.high to high) or whose value became normal,were recorded in change to normal/NC category.Participants were counted twice if participant had both decreased to low/increased to high during post-Baseline(PB).Data for worst case PB is presented.Full Safety Population(FSP) comprised of all participants who received at least 1dose of study drug(frozen liquid or lyophilized powder). 3out of 221 participants did not receive any study treatment were excluded from FSP. All participants in study were included in analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [66]
    99 [67]
    24 [68]
    Units: Participants
        Basophils, decrease to low, n=94,96,23
    2
    7
    0
        Basophils, change to normal or NC, n=94,96,23
    87
    85
    19
        Basophils, increase to high, n=94,96,23
    5
    5
    4
        Eosinophils, decrease to low, n=95,97,23
    14
    13
    0
        Eosinophils, change to normal or NC, n=95,97,23
    71
    78
    16
        Eosinophils, increase to high, n=95,97,23
    10
    8
    7
        Hematocrit, decrease to low, n=95,97,24
    10
    3
    1
        Hematocrit, change to normal or NC, n=95,97,24
    84
    94
    23
        Hematocrit, increase to high, n=95,97,24
    3
    0
    0
        MCH, decrease to low, n=95,95,21
    14
    17
    5
        MCH, change to normal or NC, n=95,95,21
    79
    68
    14
        MCH, increase to high, n=95,95,21
    2
    12
    2
        MCHC, decrease to low, n=94,96,21
    20
    28
    6
        MCHC, change to normal or NC, n=94,96,21
    70
    66
    14
        MCHC, increase to high, n=94,96,21
    5
    2
    1
        MCV,decrease to low, n=95,97,24
    12
    15
    4
        MCV, change to normal or NC, n=95,97,24
    77
    73
    18
        MCV, increase to high, n=95,97,24
    7
    10
    3
        Monocytes, decrease to low, n=95,97,24
    6
    10
    1
        Monocytes, change to normal or NC, n=95,97,24
    62
    50
    12
        Monocytes, increase to high, n=95,97,24
    28
    45
    12
        Erythrocytes, decrease to low, n=95,97,24
    4
    1
    0
        Erythrocytes, change to normal or NC, n=95,97,24
    91
    95
    21
        Erythrocytes, increase to high, n=95,97,24
    2
    1
    3
        Reticulocytes, decrease to low, n=73,65,19
    11
    15
    7
        Reticulocytes, change to normal or NC, n=73,65,19
    49
    33
    3
        Reticulocytes, increase to high, n=73,65,19
    16
    21
    10
    Notes
    [66] - Full Safety Population.
    [67] - Full Safety Population.
    [68] - Full Safety Population.
    No statistical analyses for this end point

    Secondary: Number of participants with grade change from Baseline in hematology parameters

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    End point title
    		 Number of participants with grade change from Baseline in hematology parameters
    End point description
    Blood samples were collected for the analysis of following hematology parameters: hemoglobin (Hb), lymphocyte count (Lymph), neutrophil count (Neutro), platelet count (PC), and leukocyte count (leuko).The laboratory parameters were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life–threatening consequences. Baseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with increase to grade 3 and increase to grade 4 have been presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [69]
    97 [70]
    24 [71]
    Units: Participants
        Hb, Hb increased, increase to Grade 3
    0
    0
    0
        Hb, Hb increased, increase to Grade 4
    0
    0
    0
        Hb, Anemia, increase to Grade 3
    19
    30
    5
        Hb, Anemia, increase to Grade 4
    0
    0
    0
        Lymph, Lymph count increased, increase to Grade 3
    0
    0
    0
        Lymph, Lymph count increased, increase to Grade 4
    0
    0
    0
        Lymph, Lymph count decreased, increase to Grade 3
    16
    24
    6
        Lymph, Lymph count decreased, increase to Grade 4
    5
    5
    2
        Neutro, increase to Grade 3
    4
    10
    2
        Neutro, increase to Grade 4
    6
    3
    1
        PC, increase to Grade 3
    9
    11
    1
        PC, increase to Grade 4
    13
    25
    2
        Leuko, Leukocytosis, increase to Grade 3
    0
    0
    0
        Leuko, Leukocytosis, increase to Grade 4
    0
    0
    0
        Leuko, Leuko decreased, increase to Grade 3
    5
    9
    2
        Leuko, Leuko decreased, increase to Grade 4
    3
    3
    0
    Notes
    [69] - Full Safety Population.
    [70] - Full Safety Population.
    [71] - Full Safety Population.
    No statistical analyses for this end point

    Secondary: Number of participants with change from Baseline in clinical chemistry parameters with respect to the normal range

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    End point title
    		 Number of participants with change from Baseline in clinical chemistry parameters with respect to the normal range
    End point description
    Blood samples were collected for analysis of bicarbonate, direct bilirubin(D.Bil), calcium, chloride, lactate dehydrogenase(LDH), total protein,Urea enzymatic colorimetry.Baseline is latest pre-dose assessment(Day 1) with a non-missing value, including unscheduled visits. If values were unchanged (example: high to high), or whose value became normal, were recorded in the change to normal or NC category. Participants were counted twice if the participant had both decreased to low and increased to high during post Baseline. 3 out of 221participants did not receive any study treatment, were excluded from FSP.All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [72]
    99 [73]
    24 [74]
    Units: Participants
        Bicarbonate, decrease to low, n=90,93,24
    12
    22
    4
        Bicarbonate, change to normal or NC, n=90,93,24
    67
    59
    16
        Bicarbonate, increase to high, n=90,93,24
    12
    16
    4
        D.Bil, decrease to low, n=70,72,21
    0
    2
    0
        D.Bil, change to normal or NC, n=70,72,21
    60
    60
    20
        D.Bil, increase to high, n=70,72,21
    10
    10
    1
        Calcium, decrease to low, n=95,98,24
    26
    28
    8
        Calcium, change to normal or NC, n=95,98,24
    49
    48
    9
        Calcium, increase to high, n=95,98,24
    29
    27
    9
        Chloride, decrease to low, n=94,97,24
    17
    14
    2
        Chloride, change to normal or NC, n=94,97,24
    63
    63
    20
        Chloride, increase to high, n=94,97,24
    14
    24
    2
        LDH, decrease to low, n=92,98,23
    1
    1
    0
        LDH, change to normal or NC, n=92,98,23
    46
    51
    12
        LDH, increase to high, n=92,98,23
    45
    47
    11
        Protein, decrease to low, n=94,98,24
    32
    32
    8
        Protein, change to normal or NC, n=94,98,24
    49
    58
    14
        Protein, increase to high, n=94,98,24
    17
    11
    2
        Ureaenzymaticcolorimetrydecrease tolow, n=90,93,24
    10
    13
    0
        Ureaenzymaticcolorimetrychangenormal/NCn=90,93,24
    66
    56
    16
        Ureaenzymaticcolorimetryincreasetohigh, n=90,93,24
    15
    26
    8
    Notes
    [72] - Full Safety Population.
    [73] - Full Safety Population.
    [74] - Full Safety Population.
    No statistical analyses for this end point

    Secondary: Number of participants with grade change from Baseline in clinical chemistry parameters

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    End point title
    		 Number of participants with grade change from Baseline in clinical chemistry parameters
    End point description
    Bloodsamples collected analysis of glucose(Gl),albumin,alkaline phosphatase (ALP),alanine aminotransferase(ALT), aspartate aminotransferase(AST), total bilirubin(T.Bil), creatinine kinase (CK), creatinine, gamma glutamyl transferase (GGT), potassium (Pot), magnesium (Mg), sodium (Sod), phosphate (Ph)urate &estimated glomerular filtration rate (eGFR).Grading was as per NCI-CTCAE version 4.03. Grade1: mild; Grade2: moderate; Grade3: severe or medically significant; Grade4: life–threatening consequences.Baseline is latest pre-dose assessment(Day 1) with a non-missing value, including unscheduled visits.An increase is defined as increase in CTCAE grade relative to Baseline grade. 3 out of 221participants did not receive any study treatment, were excluded from FSP. All participants in study were included in analysis (95, 99 and 24 Participants), but only those participants with data available at specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [75]
    99 [76]
    24 [77]
    Units: Participants
        Gl, Hyper, increase to Grade 3, n=94,95,24
    3
    5
    0
        Gl, Hyper, increase to Grade 4, n=94,95,24
    0
    0
    0
        Gl, Hypo, increase to Grade 3, n=94,95,24
    0
    0
    0
        Gl, Hypo, increase to Grade 4, n=94,95,24
    0
    0
    0
        Albumin, increase to Grade 3, n=94,98,24
    4
    7
    1
        Albumin, increase to Grade 4, n=94,98,24
    0
    0
    0
        ALP, increase to Grade 3, n=93,97,24
    1
    0
    0
        ALP, increase to Grade 4, n=93,97,24
    0
    0
    0
        ALT, increase to Grade 3, n=93,97,24
    0
    0
    0
        ALT, increase to Grade 4, n=93,97,24
    0
    0
    0
        AST, increase to Grade 3, n=93,96,24
    3
    7
    0
        AST, increase to Grade 4, n=93,96,24
    0
    0
    0
        T.Bil, increase to Grade 3, n=92,97,23
    0
    0
    0
        T.Bil, increase to Grade 4, n=92,97,23
    0
    0
    0
        CK, increase to Grade 3, n= 87,91,24
    1
    0
    1
        CK, increase to Grade 4, n= 87,91,24
    2
    0
    0
        Creatinine, increase to Grade 3, n= 95,97,24
    4
    3
    0
        Creatinine, increase to Grade 4, n= 95,97,24
    1
    0
    0
        GGT, increase to Grade 3, n= 91,95,24
    5
    11
    1
        GGT, increase to Grade 4, n= 91,95,24
    1
    1
    0
        Pot, Hyper,increase to Grade 3, n= 95,97,24
    0
    1
    0
        Pot, Hyper,increase to Grade 4, n= 95,97,24
    0
    0
    0
        Pot, Hypo, increase to Grade 3, n= 95,97,24
    0
    4
    1
        Pot, Hypo, increase to Grade 4, n= 95,97,24
    2
    0
    0
        Mg, Hyper, increase to Grade 3, n= 91,96,24
    3
    1
    0
        Mg, Hyper, increase to Grade 4, n= 91,96,24
    0
    0
    0
        Mg, Hypo, increase to Grade 3, n= 91,96,24
    0
    0
    0
        Mg, Hypo, increase to Grade 4, n= 91,96,24
    0
    0
    0
        Phosphate, increase to Grade 3, n= 90,93,24
    4
    8
    2
        Phosphate, increase to Grade 4, n= 90,93,24
    0
    0
    0
        Sod, Hyper, increase to Grade 3, n= 95,97,24
    0
    0
    0
        Sod, Hyper, increase to Grade 4, n= 95,97,24
    0
    0
    0
        Sod, Hypo, increase to Grade 3, n= 95,97,24
    2
    6
    1
        Sod, Hypo, increase to Grade 4, n= 95,97,24
    0
    0
    0
        Urate, increase to Grade 3, n= 93,96,24
    0
    0
    0
        Urate, increase to Grade 4, n= 93,96,24
    3
    5
    1
        eGFR, increase to Grade 3, n= 84,85,23
    8
    11
    0
        eGFR, increase to Grade 4, n= 84,85,23
    3
    1
    0
    Notes
    [75] - Full Safety Population.
    [76] - Full Safety Population.
    [77] - Full Safety Population.
    No statistical analyses for this end point

    Secondary: Number of participants with abnormal findings during physical examination

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    End point title
    		 Number of participants with abnormal findings during physical examination
    End point description
    Physical examination included assessment of the head, eyes, ears, nose, throat, skin, thyroid, lungs, cardiovascular, abdomen (liver and spleen), lymph nodes, and extremities. This analysis was planned, but data was not collected and captured in the database.
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    0 [78]
    0 [79]
    0 [80]
    Units: Participants
    Notes
    [78] - Full Safety Population.
    [79] - Full Safety Population.
    [80] - Full Safety Population.
    No statistical analyses for this end point

    Secondary: Number of participants with change from Baseline in pulse rate

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    End point title
    		 Number of participants with change from Baseline in pulse rate
    End point description
    Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Number of participants with worst case change from Baseline in pulse rate is presented. Data is categorized as: pulse rate 'decrease to <60 beats per minute [bpm]', 'increase to >100 bpm' and 'change to normal or no change'. If values were unchanged (example: increase to >100 bpm to increase to >100 bpm), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both ‘decreased to <60 bpm’ and ‘increased to >100 bpm’ during post Baseline. Data for worst-case post Baseline is presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [81]
    99 [82]
    24 [83]
    Units: Participants
        Decrease to <60
    14
    17
    6
        Change to normal or no change
    57
    55
    15
        Increase to >100
    25
    28
    3
    Notes
    [81] - Full Safety Population.
    [82] - Full Safety Population.
    [83] - Full Safety Population.
    No statistical analyses for this end point

    Secondary: Number of participants with change from Baseline in body temperature

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    End point title
    		 Number of participants with change from Baseline in body temperature
    End point description
    Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Number of participants with worst case change from Baseline in body temperature are presented. Data is categorized as: body temperature 'decrease to <=35 degrees celsius', 'increase to >=38 degrees celsius' and 'change to normal or no change'. If values were unchanged (example: increase to >=38 to increase to >=38 degrees celsius), or whose value became normal, were recorded in the 'change to normal or no change' category. Participants were counted twice if the participant had both ‘decreased to <=35’ and ‘increased to >=38 degrees celsius’ during post Baseline. Data for worst-case post Baseline is presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [84]
    98 [85]
    24 [86]
    Units: Participants
        Decrease to <=35
    1
    3
    0
        Change to normal or no change
    86
    85
    21
        Increase to >=38
    8
    10
    3
    Notes
    [84] - Full Safety Population.
    [85] - Full Safety Population.
    [86] - Full Safety Population.
    No statistical analyses for this end point

    Secondary: Number of participants with grade change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP)

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    End point title
    		 Number of participants with grade change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP)
    End point description
    SBP and DBP were graded using NCI CTCAE version 4.03. For SBP: Grade 0: <120 millimeter mercury (mmHg); Grade 1: 120-139 mmHg; Grade 2: 140-159 mmHg; Grade 3: >=160 mmHg. For DBP: Grade 0: <80 mmHg; Grade 1: 80-89 mmHg; Grade 2: 90-99 mmHg; Grade 3: >=100 mmHg. Baseline was defined as the latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. An increase is defined as an increase in CTCAE grade relative to Baseline grade. Data for worst-case post Baseline is presented. Only those participants with increase to grade 2 and increase to grade 3 have been presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [87]
    99 [88]
    24 [89]
    Units: Participants
        SBP, increase to Grade 2
    29
    41
    4
        SBP, increase to Grade 3
    14
    22
    8
        DBP, increase to Grade 2
    18
    16
    2
        DBP, increase to Grade 3
    9
    8
    1
    Notes
    [87] - Full Safety Population.
    [88] - Full Safety Population.
    [89] - Full Safety Population.
    No statistical analyses for this end point

    Secondary: Number of Participants with serious adverse events (SAEs), common (>=5%) non-serious adverse events and adverse events of special interest (AESI)

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    End point title
    		 Number of Participants with serious adverse events (SAEs), common (>=5%) non-serious adverse events and adverse events of special interest (AESI)
    End point description
    An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.SAE defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is congenital anomaly/birth defect,other situations judged by physician, is associated with liver injury and impaired liver function. Adverse events which were not Serious were considered as non-serious adverse events. Number of participants who had SAEs and common(>=5%) nonSAEs are presented. Number of participants with AESI (keratopathy, dry eye events, blurred vision, thrombocytopenia, infusion-related reactions, corneal events and neutropenia) are presented.3 out of 221 participants did not receive any study treatment and thus were excluded from the Full Safety Population.
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [90]
    99 [91]
    24 [92]
    Units: Participants
        Common non-SAE
    93
    96
    24
        SAE
    43
    53
    15
        Keratopathy
    67
    74
    23
        Dry eye events
    17
    25
    6
        Blurred vision
    24
    36
    10
        Thrombocytopenia
    36
    56
    10
        Infusion-related reactions
    20
    16
    4
        Corneal events
    68
    76
    23
        Neutropenia
    14
    28
    2
    Notes
    [90] - Full Safety Population
    [91] - Full Safety Population
    [92] - Full Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with change from Baseline in best corrected visual acuity (BCVA) test scores

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    End point title
    		 Number of participants with change from Baseline in best corrected visual acuity (BCVA) test scores
    End point description
    Baseline was defined as latest pre-dose assessment (Day 1) with non-missing value,including unscheduled visits. BCVA score was assessed individually for each eye. BCVA test scores were categorized as no change/improved vision, possible worsened vision & definite worsened vision. No change/improved vision was defined as change from Baseline <0.12 Logarithm of the Minimum Angle of Resolution (logMAR) score; a possible worsened vision was defined as change from Baseline >=0.12 to <0.3 logMAR score; a definite worsened vision was defined as a change from Baseline >=0.3 logMAR score. Data for worst-case change from Baseline is presented. 3 out of 221 participants did not receive any study treatment & thus,were excluded from Full Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    88 [93]
    94 [94]
    24 [95]
    Units: Participants
        Left eye, no change/improved vision, n=88,94,24
    35
    45
    4
        Left eye, possible worsened vision, n=88,94,24
    11
    15
    4
        Left eye, definite worsened vision, n=88,94,24
    42
    34
    16
        Right eye, no change/improved vision, n=87,93,23
    32
    38
    5
        Right eye, possible worsened vision, n=87,93,23
    21
    13
    6
        Right eye, definite worsened vision, n=87,93,23
    34
    42
    12
    Notes
    [93] - Full Safety Population.
    [94] - Full Safety Population.
    [95] - Full Safety Population.
    No statistical analyses for this end point

    Secondary: Number of participants with intraocular pressure (IOP) >=22 mmHg anytime post-Baseline

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    End point title
    		 Number of participants with intraocular pressure (IOP) >=22 mmHg anytime post-Baseline
    End point description
    Baseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. IOP was assessed individually for each eye. Number of participants with IOP >=22 mmHg anytime post-Baseline are presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population. only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    88 [96]
    93 [97]
    24 [98]
    Units: Participants
        Right eye, n=88,93,23
    17
    16
    8
        Left eye, n=88,92,24
    14
    15
    7
    Notes
    [96] - Full Safety Population
    [97] - Full Safety Population
    [98] - Full Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with shift in corneal epithelium findings from normal (Baseline) to abnormal (worst post-Baseline) for corneal epithelium (CE) and corneal stroma (CS)

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    End point title
    		 Number of participants with shift in corneal epithelium findings from normal (Baseline) to abnormal (worst post-Baseline) for corneal epithelium (CE) and corneal stroma (CS)
    End point description
    Baseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Corneal epithelium findings for CE and CS were assessed individually for each eye. Number of participants with shift in corneal epithelium findings from normal (Baseline) to abnormal (worst post-Baseline) for CE and CS are presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline and Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    92 [99]
    94 [100]
    24 [101]
    Units: Participants
        CE, Right eye, n=53,54,17
    39
    40
    16
        CE, Left eye,n=55,55,15
    39
    44
    14
        CS, Right eye,n=92,94,24
    5
    7
    3
        CS, Left eye,n=92,89,23
    8
    5
    3
    Notes
    [99] - Full Safety Population.
    [100] - Full Safety Population.
    [101] - Full Safety Population.
    No statistical analyses for this end point

    Secondary: Number of participants with shift in extraocular muscle movement from yes (Baseline) to no (worst post-Baseline)

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    End point title
    		 Number of participants with shift in extraocular muscle movement from yes (Baseline) to no (worst post-Baseline)
    End point description
    Baseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Extraocular muscle movement was assessed individually for each eye. Number of participants with shift in extraocular muscle movement from yes (Baseline) to no (worst post-Baseline) are presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline and Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [102]
    93 [103]
    23 [104]
    Units: Participants
        Right eye,n=95,93,23
    0
    4
    0
        Left eye,n=93,92,22
    0
    2
    0
    Notes
    [102] - Full Safety Population.
    [103] - Full Safety Population.
    [104] - Full Safety Population.
    No statistical analyses for this end point

    Secondary: Number of participants with shift in pupillary examination findings from normal (Baseline) to abnormal (worst post-Baseline)

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    End point title
    		 Number of participants with shift in pupillary examination findings from normal (Baseline) to abnormal (worst post-Baseline)
    End point description
    Baseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Number of participants with shift in pupillary examination findings from normal (Baseline) to abnormal (worst post-Baseline) are presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline and Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    91 [105]
    90 [106]
    23 [107]
    Units: Participants
    4
    12
    3
    Notes
    [105] - Full Safety Population.
    [106] - Full Safety Population.
    [107] - Full Safety Population.
    No statistical analyses for this end point

    Secondary: Number of participants with shift in corneal epithelium findings from no (Baseline) to yes (worst post-Baseline)

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    End point title
    		 Number of participants with shift in corneal epithelium findings from no (Baseline) to yes (worst post-Baseline)
    End point description
    Baseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Corneal epithelium findings like active edema, active opacity, corneal neovascularization (CN), corneal ulcer, epithelial microcystic edema (EME) and subepithelial were performed using a slit lamp. Number of participants with shift in corneal epithelium findings from no (Baseline) to yes (worst post-Baseline) are presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline and Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [108]
    99 [109]
    24 [110]
    Units: Participants
        Active edema, Right eye, n=94,99,24
    3
    5
    1
        Active edema, Left eye,n=95,99,24
    4
    4
    1
        Active opacity, Right eye,n=93,97,24
    3
    3
    3
        Active opacity, Left eye,n=94,95,24
    4
    4
    3
        Corneal Neovascularization, Right eye,n=93,99,24
    1
    1
    1
        Corneal Neovascularization, Left eye,n=93,99,23
    1
    0
    1
        Corneal ulcer, Right eye,n=61,60,22
    1
    1
    0
        Corneal ulcer, Left eye,n=63,61,20
    1
    2
    0
        Epithelial Microcystic Edema, Right eye,n=95,99,24
    15
    24
    9
        Epithelial Microcystic Edema, Left eye,n=95,99,23
    16
    25
    8
        Subepithelial haze, Right eye,n=95,98,24
    18
    28
    8
        Subepithelial haze, Left eye,n=95,97,23
    18
    29
    6
    Notes
    [108] - Full Safety Population.
    [109] - Full Safety Population.
    [110] - Full Safety Population.
    No statistical analyses for this end point

    Secondary: Number of participants with shift in tear break-up time from >10 seconds (Baseline) to <=5 seconds (worst post-Baseline)

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    End point title
    		 Number of participants with shift in tear break-up time from >10 seconds (Baseline) to <=5 seconds (worst post-Baseline)
    End point description
    Baseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Number of participants with shift in tear break-up time from >10 seconds (Baseline) to <=5 seconds (worst post-Baseline) are presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline and Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    34 [111]
    31 [112]
    2 [113]
    Units: Participants
        Left eye,n=34,30,2
    14
    12
    2
        Right eye,n=30,31,2
    11
    12
    1
    Notes
    [111] - Full Safety Population.
    [112] - Full Safety Population.
    [113] - Full Safety Population.
    No statistical analyses for this end point

    Secondary: Area under the concentration-time curve from time zero extrapolated to infinite time (AUC[0-infinity]) of GSK2857916 following IV dose in participants with RRMM

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    End point title
    		 Area under the concentration-time curve from time zero extrapolated to infinite time (AUC[0-infinity]) of GSK2857916 following IV dose in participants with RRMM
    End point description
    Blood samples were collected at designated timepoints. Pharmacokinetic (PK) parameters of GSK2857916 were calculated using non-compartmental methods. Full Pharmacokinetic (PK) Population comprised of all participants in the Full Safety Population who had atleast 1 non-missing PK assessment. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Cycle 1 and Cycle 3: Pre-dose, end of infusion (EOI), 2 hours and 24 hours post start of infusion (SOI) on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [114]
    99 [115]
    24 [116]
    Units: Hours*microgram per milliliter
    geometric mean (geometric coefficient of variation)
        Cycle 1,n=26,18,18
    5644 ( 39.6 )
    6495 ( 54.3 )
    6962 ( 51.4 )
        Cycle 3, n=19,21,9
    7848 ( 42.7 )
    9199 ( 45.1 )
    9694 ( 49.9 )
    Notes
    [114] - Full PK Population
    [115] - Full PK Population
    [116] - Full PK Population
    No statistical analyses for this end point

    Secondary: Area under the concentration-time curve from zero to time of last quantifiable concentration (AUC[0-tlast]) of GSK2857916 following IV dose in participants with RRMM

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    End point title
    		 Area under the concentration-time curve from zero to time of last quantifiable concentration (AUC[0-tlast]) of GSK2857916 following IV dose in participants with RRMM
    End point description
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [117]
    99 [118]
    24 [119]
    Units: Hours*microgram per milliliter
    geometric mean (geometric coefficient of variation)
        Cycle 1, n=32,21,22
    4607 ( 54.4 )
    5567 ( 51.0 )
    6293 ( 45.7 )
        Cycle 3, n=28,28,11
    6033 ( 44.7 )
    6084 ( 73.8 )
    8388 ( 46.1 )
    Notes
    [117] - Full PK Population
    [118] - Full PK Population
    [119] - Full PK Population
    No statistical analyses for this end point

    Secondary: Area under the concentration-time curve over the dosing interval (AUC[0-tau]) of GSK2857916 following IV dose in participants With RRMM

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    End point title
    		 Area under the concentration-time curve over the dosing interval (AUC[0-tau]) of GSK2857916 following IV dose in participants With RRMM
    End point description
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [120]
    99 [121]
    24 [122]
    Units: Hours*microgram per milliliter
    geometric mean (geometric coefficient of variation)
        Cycle 1, n=30,20,22
    4666 ( 45.7 )
    5678 ( 40.1 )
    5946 ( 37.2 )
        Cycle 3, n=26,24,11
    6399 ( 31.6 )
    6941 ( 34.2 )
    7593 ( 34.5 )
    Notes
    [120] - Full PK Population
    [121] - Full PK Population
    [122] - Full PK Population
    No statistical analyses for this end point

    Secondary: Maximum observed concentration (Cmax) of GSK2857916 following IV dose in participants with RRMM

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    End point title
    		 Maximum observed concentration (Cmax) of GSK2857916 following IV dose in participants with RRMM
    End point description
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [123]
    99 [124]
    24 [125]
    Units: Microgram per milliliter
    geometric mean (geometric coefficient of variation)
        Cycle 1, n=32,21,22
    42.51 ( 26.3 )
    52.03 ( 19.8 )
    51.32 ( 18.3 )
        Cycle 3, n=29,28,11
    42.35 ( 25.6 )
    45.5 ( 25.3 )
    48.06 ( 17.1 )
    Notes
    [123] - Full PK Population
    [124] - Full PK Population
    [125] - Full PK Population
    No statistical analyses for this end point

    Secondary: Time to reach maximum observed concentration (Tmax) of GSK2857916 following IV dose in participants with RRMM

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    End point title
    		 Time to reach maximum observed concentration (Tmax) of GSK2857916 following IV dose in participants with RRMM
    End point description
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [126]
    99 [127]
    24 [128]
    Units: Hours
    median (full range (min-max))
        Cycle 1, n=32,21,22
    0.780 (0.42 to 2.50)
    0.700 (0.43 to 2.15)
    0.750 (0.48 to 2.88)
        Cycle 3, n=29,28,11
    0.580 (0.47 to 2.03)
    0.715 (0.42 to 2.90)
    0.870 (0.50 to 2.02)
    Notes
    [126] - Full PK Population
    [127] - Full PK Population
    [128] - Full PK Population
    No statistical analyses for this end point

    Secondary: AUC(0-infinity) of GSK2857916 total antibody following IV dose in participants with RRMM

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    End point title
    		 AUC(0-infinity) of GSK2857916 total antibody following IV dose in participants with RRMM
    End point description
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 total antibody were calculated using non-compartmental methods. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [129]
    99 [130]
    24 [131]
    Units: Hours*microgram per milliliter
    geometric mean (geometric coefficient of variation)
        Cycle 1, n=16,10,9
    10268 ( 65.8 )
    10209 ( 64.9 )
    10170 ( 75.0 )
        Cycle 3, n=10,11,3
    20526 ( 45.1 )
    18637 ( 69.4 )
    22782 ( 161.1 )
    Notes
    [129] - Full PK Population.
    [130] - Full PK Population.
    [131] - Full PK Population.
    No statistical analyses for this end point

    Secondary: Terminal half-life (t1/2) of GSK2857916 following IV dose in participants with RRMM

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    End point title
    		 Terminal half-life (t1/2) of GSK2857916 following IV dose in participants with RRMM
    End point description
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 were calculated using non-compartmental methods. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [132]
    99 [133]
    24 [134]
    Units: Hours
    geometric mean (geometric coefficient of variation)
        Cycle 1, n=29,19,22
    164.4 ( 46.2 )
    165.8 ( 55.0 )
    196.2 ( 40.9 )
        Cycle 3, n=26,23,11
    193.7 ( 48.4 )
    214.4 ( 45.9 )
    279.5 ( 40.3 )
    Notes
    [132] - Full PK Population
    [133] - Full PK Population
    [134] - Full PK Population
    No statistical analyses for this end point

    Secondary: AUC(0-tlast) of GSK2857916 total antibody following IV dose in participants with RRMM

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    End point title
    		 AUC(0-tlast) of GSK2857916 total antibody following IV dose in participants with RRMM
    End point description
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 total antibody were calculated using non-compartmental methods. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [135]
    99 [136]
    24 [137]
    Units: Hours*microgram per milliliter
    geometric mean (geometric coefficient of variation)
        Cycle 1, n=30,19,20
    7417 ( 58.5 )
    9628 ( 52.8 )
    9017 ( 55.4 )
        Cycle 3, n=27,26,11
    10725 ( 59.4 )
    11295 ( 80.0 )
    17715 ( 61.0 )
    Notes
    [135] - Full PK Population
    [136] - Full PK Population
    [137] - Full PK Population
    No statistical analyses for this end point

    Secondary: AUC(0-tau) of GSK2857916 total antibody following IV dose in participants with RRMM

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    End point title
    		 AUC(0-tau) of GSK2857916 total antibody following IV dose in participants with RRMM
    End point description
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 total antibody were calculated using non-compartmental methods. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [138]
    99 [139]
    24 [140]
    Units: Hours*microgram per milliliter
    geometric mean (geometric coefficient of variation)
        Cycle 1, n=29,18,19
    7305 ( 41.9 )
    9566 ( 42.2 )
    9029 ( 40.2 )
        Cycle 3, n=23,24,11
    11243 ( 34.6 )
    11646 ( 38.0 )
    15311 ( 43.9 )
    Notes
    [138] - Full PK Population
    [139] - Full PK Population
    [140] - Full PK Population
    No statistical analyses for this end point

    Secondary: Tmax of GSK2857916 total antibody following IV dose in participants with RRMM

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    End point title
    		 Tmax of GSK2857916 total antibody following IV dose in participants with RRMM
    End point description
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 total antibody were calculated using non-compartmental methods.All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [141]
    99 [142]
    24 [143]
    Units: Hours
    median (full range (min-max))
        Cycle 1, n=30,19,20
    1.750 (0.42 to 2.50)
    1.870 (0.50 to 24.50)
    0.650 (0.48 to 2.17)
        Cycle 3, n=29,28,11
    0.830 (0.47 to 46.05)
    1.150 (0.42 to 2.90)
    1.750 (0.50 to 2.02)
    Notes
    [141] - Full PK Population
    [142] - Full PK Population
    [143] - Full PK Population
    No statistical analyses for this end point

    Secondary: Cmax of GSK2857916 total antibody following IV dose in participants with RRMM

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    End point title
    		 Cmax of GSK2857916 total antibody following IV dose in participants with RRMM
    End point description
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 total antibody were calculated using non-compartmental methods. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [144]
    99 [145]
    24 [146]
    Units: Microgram per milliliter
    geometric mean (geometric coefficient of variation)
        Cycle 1, n=30,19,20
    48.94 ( 30.0 )
    61.06 ( 26.9 )
    60.08 ( 18.3 )
        Cycle 3, n=29,28,11
    49.34 ( 32.9 )
    55.60 ( 26.5 )
    65.07 ( 17.4 )
    Notes
    [144] - Full PK Population
    [145] - Full PK Population
    [146] - Full PK Population
    No statistical analyses for this end point

    Secondary: t1/2 of GSK2857916 total antibody following IV dose in participants with RRMM

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    End point title
    		 t1/2 of GSK2857916 total antibody following IV dose in participants with RRMM
    End point description
    Blood samples were collected at designated timepoints. PK parameters of GSK2857916 total antibody were calculated using non-compartmental methods. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [147]
    99 [148]
    24 [149]
    Units: Hours
    geometric mean (geometric coefficient of variation)
        Cycle 1, n=29,17,19
    241.8 ( 49.3 )
    250.8 ( 70.3 )
    299.8 ( 61.0 )
        Cycle 3, n=23,23,11
    352.4 ( 52.6 )
    372.0 ( 49.6 )
    557.3 ( 91.7 )
    Notes
    [147] - Full PK Population
    [148] - Full PK Population
    [149] - Full PK Population
    No statistical analyses for this end point

    Secondary: AUC(0-infinity) of Cysteine-maleimidocaproyl monomethyl auristatin F (Cys-mcMMAF) following IV dose of GSK2857916 in participants with RRMM

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    End point title
    		 AUC(0-infinity) of Cysteine-maleimidocaproyl monomethyl auristatin F (Cys-mcMMAF) following IV dose of GSK2857916 in participants with RRMM
    End point description
    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods.All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). 66666 indicates Cys-mcMMAF was not detectable throughout the elimination phase; therefore, AUC(0-infinity) could not be estimated.
    End point type
    Secondary
    End point timeframe
    Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [150]
    99 [151]
    24 [152]
    Units: Hours*nanogram per milliliter
    geometric mean (geometric coefficient of variation)
        Cycle 1, n=27,20,19
    66666 ( 66666 )
    66666 ( 66666 )
    66666 ( 66666 )
        Cycle 3, n=26,29,11
    66666 ( 66666 )
    66666 ( 66666 )
    66666 ( 66666 )
    Notes
    [150] - Full PK Population
    [151] - Full PK Population
    [152] - Full PK Population
    No statistical analyses for this end point

    Secondary: AUC(0-tau) of Cys-mcMMAF following IV dose of GSK2857916 in participants with RRMM

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    End point title
    		 AUC(0-tau) of Cys-mcMMAF following IV dose of GSK2857916 in participants with RRMM
    End point description
    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). 66666 indicates Cys-mcMMAF was not detectable throughout the dosing interval; therefore, AUC(0-tau) could not be estimated.
    End point type
    Secondary
    End point timeframe
    Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [153]
    99 [154]
    24 [155]
    Units: Hours*nanogram per milliliter
    geometric mean (geometric coefficient of variation)
        Cycle 1, n=27,20,19
    66666 ( 66666 )
    66666 ( 66666 )
    66666 ( 66666 )
        Cycle 3, n=26,29,11
    66666 ( 66666 )
    66666 ( 66666 )
    66666 ( 66666 )
    Notes
    [153] - Full PK Population
    [154] - Full PK Population
    [155] - Full PK Population
    No statistical analyses for this end point

    Secondary: Cmax of Cys-mcMMAF following IV dose of GSK2857916 in participants with RRMM

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    End point title
    		 Cmax of Cys-mcMMAF following IV dose of GSK2857916 in participants with RRMM
    End point description
    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [156]
    99 [157]
    24 [158]
    Units: Nanogram per milliliter
    geometric mean (geometric coefficient of variation)
        Cycle 1, n=27,20,19
    0.903 ( 63.9 )
    1.148 ( 64.7 )
    1.017 ( 61.4 )
        Cycle 3, n=26,29,11
    0.660 ( 52.3 )
    0.749 ( 66.2 )
    0.656 ( 47.6 )
    Notes
    [156] - Full PK Population
    [157] - Full PK Population
    [158] - Full PK Population
    No statistical analyses for this end point

    Secondary: AUC(0-tlast) of Cysteine-maleimidocaproyl monomethyl auristatin F (Cys-mcMMAF) following IV dose of GSK2857916 in participants with RRMM

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    End point title
    		 AUC(0-tlast) of Cysteine-maleimidocaproyl monomethyl auristatin F (Cys-mcMMAF) following IV dose of GSK2857916 in participants with RRMM
    End point description
    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [159]
    99 [160]
    24 [161]
    Units: Hours*nanogram per milliliter
    geometric mean (geometric coefficient of variation)
        Cycle 1, n=27,20,19
    79.26 ( 61.0 )
    113.57 ( 58.3 )
    100.35 ( 51.8 )
        Cycle 3, n=26,29,11
    70.84 ( 46.9 )
    74.04 ( 73.0 )
    69.83 ( 36.6 )
    Notes
    [159] - Full PK Population
    [160] - Full PK Population
    [161] - Full PK Population
    No statistical analyses for this end point

    Secondary: Tmax of Cys-mcMMAF following IV dose of GSK2857916 in participants with RRMM

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    End point title
    		 Tmax of Cys-mcMMAF following IV dose of GSK2857916 in participants with RRMM
    End point description
    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods. All the participants in the study were included in the analysis (95, 99 and 24 Participants), but only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [162]
    99 [163]
    24 [164]
    Units: Hours
    median (full range (min-max))
        Cycle 1, n=27,20,19
    22.830 (1.92 to 65.63)
    23.835 (17.38 to 72.65)
    24.080 (0.97 to 69.47)
        Cycle 3, n=26,29,11
    23.235 (0.58 to 46.08)
    22.570 (0.55 to 70.98)
    22.780 (0.50 to 71.93)
    Notes
    [162] - Full PK Population
    [163] - Full PK Population
    [164] - Full PK Population
    No statistical analyses for this end point

    Secondary: t1/2 of Cys-mcMMAF following IV dose of GSK2857916 in participants with RRMM

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    End point title
    		 t1/2 of Cys-mcMMAF following IV dose of GSK2857916 in participants with RRMM
    End point description
    Blood samples were collected at designated timepoints. PK parameters of Cys-mcMMAF were calculated using non-compartmental methods.
    End point type
    Secondary
    End point timeframe
    Cycle 1 and Cycle 3: Pre-dose, EOI, 2 hours and 24 hours post SOI on Day 1, anytime on Day 4, and anytime on Day 8 to Day 15 (each cycle of 21 days)
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    95 [165]
    99 [166]
    24 [167]
    Units: Hours
    geometric mean (geometric coefficient of variation)
        Cycle 1, n=27,20,19
    66666 ( 66666 )
    66666 ( 66666 )
    66666 ( 66666 )
        Cycle 3, n=26,29,11
    66666 ( 66666 )
    66666 ( 66666 )
    66666 ( 66666 )
    Notes
    [165] - Full PK Population
    [166] - Full PK Population
    [167] - Full PK Population
    No statistical analyses for this end point

    Secondary: Titers of anti-drug antibodies against GSK2857916

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    End point title
    		 Titers of anti-drug antibodies against GSK2857916 [168]
    End point description
    Serum samples were collected for the determination of ADA using a validated ECL immunoassay. The assay involved screening, confirmation and titration steps. If serum samples contained ADA, they were further analyzed for the specificity of antibodies by a confirmation assay. Confirmed positive samples were titrated to obtain the titers of antibodies. Titers of anti-drug antibodies against GSK2857916 is presented. No participant was found with positive results for ADA test in arm GSK2857916 3.4 mg/kg (Lyophilized). Hence, titer values was not presented for the arm. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    Notes
    [168] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: There are no statistical data to report.
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid)
    Number of subjects analysed
    4 [169]
    2 [170]
    Units: Titers
        arithmetic mean (standard deviation)
    125.0 ( 50.00 )
    100.0 ( 0.00 )
    Notes
    [169] - Full Safety Population.
    [170] - Full Safety Population.
    No statistical analyses for this end point

    Secondary: Number of participants with at least one confirmed positive post-Baseline anti-drug antibody (ADA) result

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    End point title
    		 Number of participants with at least one confirmed positive post-Baseline anti-drug antibody (ADA) result
    End point description
    Serum samples were collected for the determination of anti-GSK2857916 antibodies (ADA) using a validated electrochemiluminescent (ECL) immunoassay. The assay involved screening, confirmation and titration steps. If serum samples tested positive in the screening assay, they were considered 'potentially positive' and were further analyzed for the specificity using the confirmation assay. Samples that confirmed positive in the confirmation assay were reported as 'positive'. Confirmed positive ADA samples were further characterized in the titration assay to quasi-quantitate the amount of ADA in the sample. Additionally, confirmed positive ADA samples were also tested in a validated neutralizing antibody assay to determine the potential neutralizing activity of the ADA. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    89 [171]
    92 [172]
    24 [173]
    Units: Participants
    2
    0
    0
    Notes
    [171] - Full Safety Population.
    [172] - Full Safety Population.
    [173] - Full Safety Population.
    No statistical analyses for this end point

    Secondary: Number of participants with symptomatic AEs measured by patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE)

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    End point title
    		 Number of participants with symptomatic AEs measured by patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE)
    End point description
    The PRO-CTCAE is a patient-reported outcome measure developed to evaluate symptomatic toxicity in participants on cancer clinical trials. It included symptomatic toxicities drawn from the CTCAE like blurred vision, chills, constipation, decreased appetite, fatigue, general pain, heart palpitations, mouth/throat sores, nausea, nosebleed, shortness of breath, vomiting and watery eyes. Items were scored individually on a 0 to 4 scale for severity, frequency and interference. Number of participants with symptomatic AEs (those who had a maximum post-Baseline rating greater than 0, example; 1, 2, 3, or 4) measured by PRO-CTCAE are presented. Full Safety Population.
    End point type
    Secondary
    End point timeframe
    Up to 186 weeks
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    84 [174]
    92 [175]
    22 [176]
    Units: Participants
        Blurred Vision , n= 84,92,22
    59
    67
    19
        Chills, n=43,42,13
    39
    36
    12
        Constipation,n=84,92, 22
    42
    47
    17
        Decreased Appetite, n=84,92, 22
    60
    65
    16
        Fatigue, n=84,92, 22
    81
    87
    21
        General Pain, n= 79, 80, 20
    78
    80
    19
        Heart Palpitations,n=37, 37, 14
    35
    33
    14
        Mouth/Throat Sores,n=84,92, 22
    28
    25
    8
        Nausea,n=48, 52, 11
    47
    50
    11
        Nosebleed,n=23, 33, 6
    22
    33
    6
        Shortness Of Breath, n=84,92, 22
    60
    58
    17
        Vomiting,n=21, 28, 6
    20
    28
    5
        Watery Eyes,n=84,92, 22
    50
    59
    19
    Notes
    [174] - Full Safety Population.
    [175] - Full Safety Population.
    [176] - Full Safety Population.
    No statistical analyses for this end point

    Secondary: Worst change from Baseline in National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) overall composite score

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    End point title
    		 Worst change from Baseline in National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) overall composite score
    End point description
    The NEI-VFQ-25 consisted of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question to assess the impact of ocular toxicity on visual function. Items were coded to a 0 to 100 scale and averaged to calculate domains. Domain scores ranged from 0 to 100; higher scores are better. Therefore, increase in score means improvement. Baseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for worst-case post Baseline is presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and up to Week 186
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    83 [177]
    92 [178]
    22 [179]
    Units: Scores on a scale
        arithmetic mean (standard deviation)
    -20.0 ( 22.60 )
    -19.6 ( 21.66 )
    -23.1 ( 23.82 )
    Notes
    [177] - Full Safety Population
    [178] - Full Safety Population
    [179] - Full Safety Population
    No statistical analyses for this end point

    Secondary: Worst change from Baseline in Ocular Surface Disease Index (OSDI) total score

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    End point title
    		 Worst change from Baseline in Ocular Surface Disease Index (OSDI) total score
    End point description
    The OSDI is a 12-item questionnaire designed to assess both the frequency of dry eye symptoms and their impact on vision-related functioning. The total OSDI score was calculated as (sum of scores for all questions answered*100) divided by (total number of questions answered*4). Domain scores ranged from 0 to 100; lower scores are better. Therefore, decrease in score from Baseline means improvement. Baseline was defined as latest pre-dose assessment (Day 1) with a non-missing value, including unscheduled visits. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value. Data for worst-case post Baseline is presented. 3 participants out of 221 participants did not receive any study treatment and thus, were excluded from the Full Safety Population. Only those participants with data available at the specified data points were analyzed.
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and up to Week 186
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    83 [180]
    92 [181]
    22 [182]
    Units: Scores on a scale
        arithmetic mean (standard deviation)
    26.9 ( 29.61 )
    28.2 ( 28.49 )
    35.0 ( 29.02 )
    Notes
    [180] - Full Safety Population
    [181] - Full Safety Population
    [182] - Full Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core module (EORTC QLQ-C30) score

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    End point title
    		 Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire 30-item Core module (EORTC QLQ-C30) score
    End point description
    The EORTC QLQ-C30:(physicalfunctioning [PF],rolefunctioning [RF],cognitivefunctioning [CF],emotionalfunctioning [EF]&socialfunctioning [SF]),(fatigue,pain &nausea/vomiting [N/V]),global health status (GHS)/Quality-of-Life (QoL) scale,(constipation,diarrhoea,insomnia,dyspnoea,appetite loss [AL] & financial difficulties [FD]). Response options:1 to 4. Scores were averaged & transformed to 0 to 100,high score for functional scales/ GHS/QoL-better functioning ability or health-related quality-of-life (HRQoL),whereas high score for symptom scales/ single items-significant symptomatology.Baseline was defined as latest predose assessment with non-missing value,including unscheduled visits.Change from Baseline was calculated by post-dose visit minus Baseline value.Only those participants with data available at specified data points were analyzed(represented by n=X in the category titles).99999 indicates data is not available.77777 indicates SD could not be calculated for single participant
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 07, Week 13, Week 19, Week 25, Week 31, Week 37, Week 43, Week 61, Week 79, Week 97, Week 115, Week 133, Week 151, Week 169, and Week 186
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    97 [183]
    99 [184]
    25 [185]
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        GHS/QoL,Week 07,n=48,47,17
    -0.7 ( 20.47 )
    -4.1 ( 18.54 )
    1.5 ( 23.80 )
        GHS/QoL,Week 13,n=29,29,16
    -3.2 ( 18.42 )
    6.0 ( 16.50 )
    1.0 ( 14.23 )
        GHS/QoL,Week 19,n=19,27,10
    -2.2 ( 13.84 )
    3.7 ( 20.19 )
    0 ( 12.42 )
        GHS/QoL,Week 25,n=20,23,7
    -4.6 ( 16.10 )
    -2.5 ( 20.94 )
    7.1 ( 8.91 )
        GHS/QoL,Week 31,n=15,18,7
    -2.2 ( 14.59 )
    5.1 ( 20.44 )
    2.4 ( 14.20 )
        GHS/QoL,Week 37,n=15,13,5
    -1.7 ( 14.50 )
    1.9 ( 21.29 )
    11.7 ( 4.56 )
        GHS/QoL,Week 43,n=15,14,4
    -4.4 ( 14.04 )
    10.7 ( 15.82 )
    12.5 ( 10.76 )
        GHS/QoL,Week 61,n=11,11,3
    -3.8 ( 17.23 )
    -5.3 ( 13.58 )
    0.0 ( 0.00 )
        GHS/QoL,Week 79,n=3,2,1
    2.8 ( 24.06 )
    16.7 ( 23.57 )
    16.7 ( 77777 )
        GHS/QoL,Week 97,n=4,5,3
    8.3 ( 11.79 )
    1.7 ( 25.28 )
    8.3 ( 0.00 )
        GHS/QoL,Week 115,n=2,6,3
    -4.2 ( 17.68 )
    1.4 ( 22.00 )
    2.8 ( 4.81 )
        GHS/QoL,Week 133,n=2,1,2
    -4.2 ( 17.68 )
    33.3 ( 77777 )
    -8.3 ( 11.79 )
        GHS/QoL,Week 151,n=0,2,0
    99999 ( 99999 )
    8.3 ( 35.36 )
    99999 ( 99999 )
        GHS/QoL,Week 169,n=0,1,0
    99999 ( 99999 )
    33.3 ( 77777 )
    99999 ( 99999 )
        GHS/QoL,Week 186n=41,46,17
    -8.1 ( 19.50 )
    -11.6 ( 22.46 )
    -3.9 ( 15.34 )
        PF,,Week 07,n=48,47,17
    4.4 ( 15.70 )
    -1.0 ( 21.93 )
    -5.5 ( 24.18 )
        PF,Week 13, n=29,29,16
    0.7 ( 14.62 )
    4.1 ( 11.19 )
    -12.5 ( 23.84 )
        PF,,Week 19,n=19,27,10
    0.4 ( 13.78 )
    6.2 ( 24.87 )
    -4.0 ( 14.81 )
        PF,Week 25, n=20,23,7
    1.3 ( 12.16 )
    5.5 ( 25.08 )
    -1.0 ( 14.62 )
        PF,Week 31,n=15,18,7
    -2.7 ( 8.66 )
    9.3 ( 22.88 )
    4.8 ( 10.69 )
        PF, Week 37,n=15,13, 5
    4.0 ( 11.76 )
    15.4 ( 25.15 )
    10.7 ( 18.62 )
        PF, Week 43,n=15,14, 4
    3.1 ( 11.23 )
    14.8 ( 26.04 )
    6.7 ( 27.22 )
        PF, Week 61,n=11,11, 3
    4.2 ( 12.39 )
    9.7 ( 22.18 )
    15.6 ( 3.85 )
        PF, Week 79,n=3,2, 2
    2.2 ( 3.85 )
    10.0 ( 4.71 )
    10.0 ( 4.71 )
        PF, Week 97,n=4,5, 3
    0.0 ( 9.43 )
    0.0 ( 9.43 )
    -2.2 ( 23.41 )
        PF, Week 115,n=2,6, 3
    3.3 ( 4.71 )
    4.4 ( 13.11 )
    4.4 ( 10.18 )
        PF, Week 133,n=2,1, 2
    3.3 ( 4.71 )
    13.3 ( 77777 )
    -6.7 ( 18.86 )
        PF, Week 151,n=0,2,0
    99999 ( 99999 )
    0.0 ( 18.86 )
    99999 ( 99999 )
        PF, Week 169, n=0,1,0
    4.7 ( 20.98 )
    13.3 ( 77777 )
    -1.0 ( 20.81 )
        PF, Week 186,n=41,46,17
    -0.8 ( 21.20 )
    -6.2 ( 21.29 )
    -13.3 ( 24.38 )
        RF,Week 07,n=48,47,17
    0.3 ( 33.24 )
    -6.0 ( 35.68 )
    -7.8 ( 25.08 )
        RF,Week 13,n=29,29,16
    2.3 ( 33.55 )
    -0.6 ( 32.88 )
    -6.3 ( 30.96 )
        RF,Week 19,n=19,27,10
    -4.4 ( 31.35 )
    1.9 ( 36.50 )
    -5.0 ( 23.64 )
        RF,Week 25,n=20,23,7
    2.5 ( 32.57 )
    0.0 ( 32.57 )
    11.9 ( 32.93 )
        RF,Week 31,n=15,18,7
    8.9 ( 24.29 )
    3.7 ( 34.09 )
    7.1 ( 21.21 )
        RF,Week 37,n=15,13,5
    8.9 ( 29.46 )
    3.8 ( 39.76 )
    20.0 ( 27.39 )
        RF,Week 43,n=15,14,4
    8.9 ( 30.12 )
    11.9 ( 32.31 )
    8.3 ( 21.52 )
        RF,Week 61,n=11,11,3
    12.1 ( 36.58 )
    -3.0 ( 29.64 )
    16.7 ( 16.67 )
        RF,Week 79,n=3,2,2
    5.6 ( 34.69 )
    8.3 ( 11.79 )
    8.3 ( 35.36 )
        RF,Week 97,n=4,5,3
    -4.2 ( 43.83 )
    -6.7 ( 19.00 )
    5.6 ( 34.69 )
        RF,Week 115,n=2,6,3
    0.0 ( 47.14 )
    -5.6 ( 17.21 )
    16.7 ( 44.10 )
        RF,Week 133,n=2,1,2
    8.3 ( 35.36 )
    16.7 ( 77777 )
    25.0 ( 11.79 )
        RF,Week 151,n=0,2,0
    99999 ( 99999 )
    -16.7 ( 23.57 )
    99999 ( 99999 )
        RF,Week 169,n=0,1,0
    -7.7 ( 23.78 )
    0.0 ( 77777 )
    -1.4 ( 24.97 )
        RF,Week 186,n=41,46,17
    -0.4 ( 30.84 )
    -8.3 ( 33.66 )
    -16.7 ( 30.62 )
        EF,Week 07,n=48,47,17
    1.4 ( 18.86 )
    1.4 ( 27.10 )
    -4.4 ( 21.27 )
        EF,Week 13,n=29,29,16
    -2.0 ( 23.00 )
    -0.0 ( 25.00 )
    -9.4 ( 23.35 )
        EF,Week 19,n=19,27,10
    0.4 ( 19.93 )
    3.1 ( 20.30 )
    -1.7 ( 21.08 )
        EF,Week 25, n=20, 23, 7
    -4.6 ( 21.20 )
    4.0 ( 20.39 )
    -2.4 ( 14.20 )
        EF,Week 37, n=15,13, 5
    1.7 ( 13.44 )
    9.6 ( 23.29 )
    13.3 ( 16.24 )
        EF,Week 43, n=15,14, 4
    0.0 ( 18.90 )
    8.3 ( 27.74 )
    4.2 ( 4.81 )
        EF,Week 61, n=11,11, 3
    6.8 ( 12.81 )
    -5.3 ( 16.36 )
    19.4 ( 12.73 )
        EF,Week 79, n=3,2,2
    2.8 ( 4.81 )
    8.3 ( 11.79 )
    16.7 ( 23.57 )
        EF,Week 97, n=4,5,3
    2.1 ( 10.49 )
    1.7 ( 25.95 )
    8.3 ( 16.67 )
        EF,Week 115, n=2,6,3
    0.0 ( 23.57 )
    -2.8 ( 11.39 )
    11.1 ( 12.73 )
        EF,Week 133, n=2,1,2
    -4.2 ( 29.46 )
    16.7 ( 77777 )
    8.3 ( 23.57 )
        EF,Week 169, n=0,1,0
    99999 ( 99999 )
    16.7 ( 77777 )
    99999 ( 99999 )
        EF,Week 186, n=41,46,17
    -6.7 ( 24.45 )
    -6.2 ( 21.04 )
    -10.8 ( 17.37 )
        CF,Week 07,n=48,47,17
    4.5 ( 20.55 )
    -2.1 ( 21.03 )
    -1.0 ( 20.81 )
        CF,Week 13,n=29,29,16
    2.3 ( 23.45 )
    -1.1 ( 15.39 )
    -15.6 ( 27.53 )
        CF,Week 19,n=19,27,10
    -1.8 ( 26.58 )
    -0.6 ( 22.87 )
    -6.7 ( 21.08 )
        CF,Week 25, n=20, 23, 7
    -1.7 ( 27.52 )
    1.4 ( 21.27 )
    -11.9 ( 18.54 )
        CF,Week 31, n=15,18, 7
    6.7 ( 23.40 )
    -3.7 ( 19.43 )
    -4.8 ( 12.60 )
        CF,Week 37, n=15,13, 5
    3.3 ( 22.00 )
    3.8 ( 13.87 )
    3.3 ( 13.94 )
        CF,Week 43, n=15,14, 4
    2.2 ( 24.29 )
    1.2 ( 10.26 )
    -4.2 ( 8.33 )
        CF,Week 61, n=11,11, 3
    10.6 ( 27.15 )
    -1.5 ( 15.73 )
    5.6 ( 9.62 )
        CF,Week 79, n=3,2,2
    11.1 ( 19.25 )
    -25.0 ( 35.36 )
    8.3 ( 11.79 )
        CF,Week 97, n=4,5,3
    -4.2 ( 25.00 )
    -16.7 ( 33.33 )
    0.0 ( 16.67 )
        CF,Week 115, n=2,6,3
    0.0 ( 23.57 )
    -0.0 ( 18.26 )
    11.1 ( 9.62 )
        CF,Week 133, n=2,1,2
    -8.3 ( 35.36 )
    0.0 ( 77777 )
    8.3 ( 11.79 )
        CF,Week 151, n=0,2,0
    99999 ( 99999 )
    -16.7 ( 23.57 )
    99999 ( 99999 )
        CF,Week 169, n=0,1,0
    99999 ( 99999 )
    0.0 ( 77777 )
    99999 ( 99999 )
        CF,Week 186, n=41,46,17
    -3.3 ( 25.88 )
    -11.2 ( 26.07 )
    -9.8 ( 13.25 )
        SF,Week 07,n=48,47,17
    3.8 ( 29.02 )
    1.1 ( 32.49 )
    -1.0 ( 33.58 )
        SF,Week 13,n=29,29,16
    -4.0 ( 28.75 )
    1.7 ( 28.64 )
    -7.3 ( 31.01 )
        SF,Week 19,n=19,27,10
    -6.1 ( 28.44 )
    5.6 ( 28.50 )
    -6.7 ( 28.54 )
        SF,Week 25, n=20, 23, 7
    -6.7 ( 26.71 )
    13.8 ( 22.84 )
    2.4 ( 32.53 )
        SF,Week 31, n=15,18, 7
    2.2 ( 16.51 )
    15.7 ( 31.56 )
    2.4 ( 24.40 )
        SF,Week 37, n=15,13, 5
    2.2 ( 21.70 )
    16.7 ( 29.66 )
    20.0 ( 21.73 )
        SF,Week 43, n=15,14, 4
    -1.1 ( 17.21 )
    20.2 ( 30.08 )
    16.7 ( 23.57 )
        SF,Week 61, n=11,11, 3
    7.6 ( 32.80 )
    -1.5 ( 17.41 )
    33.3 ( 16.67 )
        SF,Week 79, n=3,2,2
    5.6 ( 19.25 )
    8.3 ( 35.36 )
    25.0 ( 35.36 )
        SF,Week 97, n=4,5,3
    -4.2 ( 43.83 )
    16.7 ( 20.41 )
    33.3 ( 16.67 )
        SF,Week 115, n=2,6,3
    16.7 ( 23.57 )
    2.8 ( 24.53 )
    27.8 ( 25.46 )
        SF,Week 133, n=2,1,2
    16.7 ( 23.57 )
    33.3 ( 77777 )
    41.7 ( 11.79 )
        SF,Week 151, n=0,2,0
    99999 ( 99999 )
    16.7 ( 23.57 )
    99999 ( 99999 )
        SF,Week 169, n=0,1,0
    99999 ( 99999 )
    33.3 ( 77777 )
    99999 ( 99999 )
        SF,Week 186, n=41,46,17
    -4.1 ( 26.56 )
    -10.1 ( 25.93 )
    -8.8 ( 31.80 )
        Fatigue,Week 07,n=48,47,17
    -3.7 ( 21.90 )
    -0.5 ( 23.74 )
    -5.2 ( 20.83 )
        Fatigue,Week 13,n=29,29,16
    -7.7 ( 23.78 )
    -7.7 ( 19.27 )
    -1.4 ( 24.97 )
        Fatigue,Week 19,n=19,27,10
    -0.6 ( 22.67 )
    -2.9 ( 22.77 )
    -11.1 ( 15.71 )
        Fatigue,Week 25, n=20, 23, 7
    3.3 ( 23.67 )
    -2.4 ( 21.70 )
    -11.1 ( 16.97 )
        Fatigue,Week 31, n=15,18, 7
    -0.7 ( 21.61 )
    -11.7 ( 22.05 )
    -12.7 ( 18.62 )
        Fatigue,Week 37, n=15,13, 5
    -9.6 ( 18.24 )
    -13.7 ( 24.07 )
    -20.0 ( 14.49 )
        Fatigue,Week 43, n=15,14, 4
    -12.6 ( 17.25 )
    -10.3 ( 32.16 )
    -22.2 ( 12.83 )
        Fatigue,Week 61, n=11,11, 3
    -12.1 ( 24.07 )
    3.0 ( 22.82 )
    -11.1 ( 0.00 )
        Fatigue,Week 79, n=3,2,2
    -22.2 ( 11.11 )
    -16.7 ( 7.86 )
    5.6 ( 23.57 )
        Fatigue,Week 97, n=4,5,3
    -5.6 ( 26.45 )
    6.7 ( 20.18 )
    -25.9 ( 23.13 )
        Fatigue,Week 115, n=2,6,3
    -16.7 ( 23.57 )
    -3.7 ( 15.18 )
    -18.5 ( 23.13 )
        Fatigue,Week 133, n=2,1,2
    -5.6 ( 39.28 )
    -22.2 ( 77777 )
    -22.2 ( 15.71 )
        Fatigue,Week 151, n=0,2,0
    99999 ( 99999 )
    16.7 ( 23.57 )
    99999 ( 99999 )
        Fatigue,Week 169, n=0,1,0
    99999 ( 99999 )
    0.0 ( 77777 )
    99999 ( 99999 )
        Fatigue,Week 186, n=41,46,17
    -1.6 ( 23.12 )
    4.1 ( 23.35 )
    6.5 ( 22.93 )
        N/V,Week 07,n=46,46,17
    2.4 ( 14.17 )
    4.3 ( 17.88 )
    2.0 ( 14.29 )
        N/V,Week 13,n=29,29,16
    2.3 ( 13.16 )
    1.1 ( 9.89 )
    7.3 ( 25.80 )
        N/V,Week 19,n=19,27,10
    -1.8 ( 15.61 )
    -1.2 ( 15.96 )
    1.7 ( 5.27 )
        N/V,Week 25,n=20,23,7
    5.0 ( 12.21 )
    -0.7 ( 12.79 )
    -4.8 ( 12.60 )
        N/V,Week 31,n=15,18,7
    -3.3 ( 6.90 )
    1.9 ( 7.86 )
    -2.4 ( 15.00 )
        N/V,Week 37,n=15,13, 5
    -6.7 ( 16.43 )
    2.6 ( 11.48 )
    0.0 ( 0.00 )
        N/V,Week 43,n=15,14,4
    -7.8 ( 15.26 )
    1.2 ( 7.91 )
    -8.3 ( 16.67 )
        N/V,Week 61, n=11,11,3
    -4.5 ( 10.78 )
    4.5 ( 7.78 )
    0.0 ( 16.67 )
        N/V,Week 79, n=3,2,2
    0.0 ( 0.00 )
    0.0 ( 0.00 )
    0.0 ( 0.00 )
        N/V,Week 97, n=4,5,3
    0.0 ( 0.00 )
    0.0 ( 0.00 )
    -11.1 ( 19.25 )
        N/V,Week 115, n=2,6,3
    0.0 ( 0.00 )
    0.0 ( 0.00 )
    -16.7 ( 16.67 )
        N/V,Week 133, n=2,1,2
    0.0 ( 0.00 )
    0.0 ( 77777 )
    -25.0 ( 11.79 )
        N/V, Week 151, n=0,2,0
    99999 ( 99999 )
    0.0 ( 0.00 )
    99999 ( 99999 )
        N/V, Week 169, n=0,1,0
    99999 ( 99999 )
    0.0 ( 77777 )
    99999 ( 99999 )
        N/V, Week 186, n=41,46,17
    5.7 ( 24.04 )
    3.3 ( 18.47 )
    1.0 ( 21.63 )
        Pain,Week 07,n=48,47,17
    -3.1 ( 28.69 )
    -1.1 ( 28.32 )
    8.8 ( 28.33 )
        Pain,Week 13,n=29,28,16
    -4.0 ( 26.97 )
    -2.3 ( 25.48 )
    5.2 ( 27.02 )
        Pain,Week 19,n=19,27,10
    4.4 ( 19.12 )
    -8.6 ( 31.14 )
    1.7 ( 30.88 )
        Pain,Week 25,n=20,23,7
    2.5 ( 18.16 )
    -1.4 ( 24.57 )
    -0.0 ( 28.87 )
        Pain,Week 31,n=15,18,7
    4.4 ( 19.38 )
    -0.9 ( 23.90 )
    2.4 ( 35.26 )
        Pain,Week 37,n=15,13,5
    -2.2 ( 21.70 )
    -10.3 ( 24.09 )
    -3.3 ( 24.72 )
        Pain,Week 43,n=15,14,4
    -2.2 ( 15.26 )
    -8.3 ( 24.24 )
    4.2 ( 36.96 )
        Pain,Week 61,n=11,11,3
    -10.6 ( 18.67 )
    -0.0 ( 21.08 )
    -5.6 ( 34.69 )
        Pain,Week 79,n=3,2,2
    -16.7 ( 16.67 )
    0.0 ( 23.57 )
    8.3 ( 58.93 )
        Pain,Week 97,n=4,5,3
    -4.2 ( 20.97 )
    26.7 ( 22.36 )
    -0.0 ( 44.10 )
        Pain,Week 115,n=2,6, 3
    0.0 ( 0.00 )
    8.3 ( 27.39 )
    5.6 ( 53.58 )
        Pain,Week 133,n=2,1, 2
    0.0 ( 0.00 )
    16.7 ( 77777 )
    16.7 ( 70.71 )
        Pain,Week 151,n=0,2, 0
    99999 ( 99999 )
    33.3 ( 23.57 )
    99999 ( 99999 )
        Pain,Week 169,n=0,1, 0
    99999 ( 99999 )
    16.7 ( 77777 )
    99999 ( 99999 )
        Pain,Week 186,n=41,46, 17
    1.6 ( 27.59 )
    1.4 ( 25.29 )
    16.7 ( 31.73 )
        Dyspnoea,Week 07,n=48,47,17
    -2.1 ( 22.18 )
    2.1 ( 14.59 )
    -7.8 ( 18.74 )
        Dyspnoea,Week 13,n=29,29,16
    -1.1 ( 18.86 )
    1.1 ( 22.68 )
    2.1 ( 30.96 )
        Dyspnoea,Week 19,n=19,27,10
    -5.3 ( 20.07 )
    3.7 ( 25.04 )
    -16.7 ( 28.33 )
        Dyspnoea,Week 25,n=20,23,7
    -1.7 ( 20.16 )
    4.3 ( 18.27 )
    0.0 ( 27.22 )
        Dyspnoea,Week 31,n=15, 18, 7
    -6.7 ( 18.69 )
    0.0 ( 16.17 )
    -9.5 ( 16.27 )
        Dyspnoea,Week 37,n=15, 13, 5
    -8.9 ( 19.79 )
    12.8 ( 16.88 )
    -26.7 ( 27.89 )
        Dyspnoea,Week 43,n=15, 14, 4
    -6.7 ( 22.54 )
    2.4 ( 15.82 )
    -25.0 ( 31.91 )
        Dyspnoea,Week 61,n=11,11,3
    0.0 ( 21.08 )
    3.0 ( 17.98 )
    -33.3 ( 33.33 )
        Dyspnoea,Week 79,n=3, 2,2
    0.0 ( 0.00 )
    0.0 ( 0.00 )
    -33.3 ( 47.14 )
        Dyspnoea,Week 97,n=4, 5,3
    16.7 ( 19.25 )
    0.0 ( 23.57 )
    -22.2 ( 38.49 )
        Dyspnoea,Week 115,n=2, 6,3
    0.0 ( 0.00 )
    5.6 ( 13.61 )
    -33.3 ( 33.33 )
        Dyspnoea,Week 133,n=2,1,2
    0.0 ( 0.00 )
    0.0 ( 77777 )
    -16.7 ( 23.57 )
        Dyspnoea,Week 151,n=0,2,0
    99999 ( 99999 )
    0.0 ( 0.00 )
    99999 ( 99999 )
        Dyspnoea,Week 169,n=0,1,0
    99999 ( 99999 )
    0.0 ( 77777 )
    99999 ( 99999 )
        Dyspnoea,Week 186,n=41, 46,17
    0.0 ( 19.72 )
    12.3 ( 24.70 )
    -9.8 ( 25.72 )
        Insomnia,Week 07,n=48, 47, 17
    -6.2 ( 29.70 )
    -2.8 ( 26.77 )
    -0.0 ( 23.57 )
        Insomnia,Week 13,n=29,29,16
    0.0 ( 26.73 )
    -1.1 ( 25.95 )
    -0.0 ( 34.43 )
        Insomnia,Week 19,n=19,27,10
    -8.8 ( 24.45 )
    -4.9 ( 28.80 )
    -13.3 ( 35.83 )
        Insomnia,Week 25,n=20,23,7
    -5.0 ( 32.94 )
    -7.2 ( 22.38 )
    0.0 ( 33.33 )
        Insomnia,Week 31,n=15,18,7
    -17.8 ( 27.79 )
    -9.3 ( 33.93 )
    4.8 ( 40.50 )
        Insomnia,Week 37,n=15,13,5
    -15.6 ( 33.01 )
    -10.3 ( 16.01 )
    -13.3 ( 38.01 )
        Insomnia,Week 43,n=15,14,4
    -15.6 ( 30.52 )
    -4.8 ( 22.10 )
    -0.0 ( 47.14 )
        Insomnia,Week 61,n=11,11,3
    -9.1 ( 15.57 )
    -9.1 ( 21.56 )
    -11.1 ( 19.25 )
        Insomnia,Week 79,n=3,2,2
    0.0 ( 33.33 )
    16.7 ( 23.57 )
    -33.3 ( 47.14 )
        Insomnia,Week 97,n=4,5,3
    -25.0 ( 31.91 )
    -6.7 ( 14.91 )
    -44.4 ( 38.49 )
        Insomnia,Week 115,n=2,6,3
    -33.3 ( 47.14 )
    5.6 ( 25.09 )
    -33.3 ( 33.33 )
        Insomnia,Week 133,n=2,1,2
    -16.7 ( 70.71 )
    0.0 ( 77777 )
    -66.7 ( 0.00 )
        Insomnia,Week 151,n=0,2,0
    99999 ( 99999 )
    0.0 ( 0.00 )
    99999 ( 99999 )
        Insomnia,Week 169,n=0,1,0
    99999 ( 99999 )
    0.0 ( 77777 )
    99999 ( 99999 )
        Insomnia,Week 186,n=41,46,17
    2.4 ( 33.66 )
    -2.9 ( 32.07 )
    2.0 ( 29.98 )
        AL,Week 07,n=48,47,17
    4.9 ( 24.78 )
    2.1 ( 29.00 )
    2.0 ( 27.56 )
        AL,Week 13,n=29,29,16
    8.0 ( 29.08 )
    -2.3 ( 25.09 )
    12.5 ( 26.87 )
        AL,Week 19,n=19,27,10
    0.0 ( 24.85 )
    -0.0 ( 38.12 )
    -3.3 ( 10.54 )
        AL,Week 25,n=20, 23, 7
    6.7 ( 31.72 )
    -5.8 ( 21.68 )
    -9.5 ( 16.27 )
        AL,Week 31,n=15,18, 7
    -8.9 ( 15.26 )
    0.0 ( 19.80 )
    -4.8 ( 23.00 )
        AL,Week 37,n=15,13,5
    -4.4 ( 17.21 )
    -5.1 ( 22.96 )
    -20.0 ( 18.26 )
        AL,Week 43,n=15,14,4
    -4.4 ( 17.21 )
    -9.5 ( 24.21 )
    -25.0 ( 16.67 )
        AL,Week 61,n=11,11,3
    -6.1 ( 20.10 )
    0.0 ( 36.51 )
    11.1 ( 19.25 )
        AL,Week 79,n=3,2,2
    -33.3 ( 0.00 )
    16.7 ( 23.57 )
    16.7 ( 23.57 )
        AL,Week 97,n=4,5,3
    -8.3 ( 16.67 )
    13.3 ( 18.26 )
    0.0 ( 33.33 )
        AL,Week 115,n=2,6,3
    0.0 ( 0.00 )
    0.0 ( 21.08 )
    0.0 ( 33.33 )
        AL,Week 133,n=2,1,2
    0.0 ( 0.00 )
    0.0 ( 77777 )
    -16.7 ( 23.57 )
        AL,Week 151,n=0,2,0
    99999 ( 99999 )
    33.3 ( 47.14 )
    99999 ( 99999 )
        AL,Week 169,n=0,1,0
    99999 ( 99999 )
    0.0 ( 77777 )
    99999 ( 99999 )
        AL,Week 186,n=41,46,17
    5.7 ( 24.61 )
    -0.0 ( 32.96 )
    2.0 ( 21.96 )
        Constipation,Week 07,n=48,47,17
    1.4 ( 22.76 )
    -2.1 ( 17.59 )
    -7.8 ( 25.08 )
        Constipation,Week 13,n=29,29,16
    0.0 ( 25.20 )
    -5.7 ( 17.97 )
    8.3 ( 31.03 )
        Constipation,Week 19,n=19,27,10
    -7.0 ( 21.02 )
    1.2 ( 17.25 )
    -3.3 ( 18.92 )
        Constipation,Week 25,n=20,23,7
    -3.3 ( 14.91 )
    -1.4 ( 18.74 )
    -14.3 ( 32.53 )
        Constipation,Week 31,n=15,18,7
    -4.4 ( 11.73 )
    -3.7 ( 15.71 )
    -19.0 ( 26.23 )
        Constipation,Week 37,n=15,13,5
    2.2 ( 23.46 )
    -5.1 ( 22.96 )
    -20.0 ( 38.01 )
        Constipation,Week 43,n=15,14,4
    -4.4 ( 17.21 )
    -2.4 ( 20.52 )
    -16.7 ( 43.03 )
        Constipation,Week 61,n=11,11,3
    0.0 ( 14.91 )
    -9.1 ( 30.15 )
    -11.1 ( 38.49 )
        Constipation,Week 79,n=3,2,2
    0.0 ( 0.00 )
    0.0 ( 0.00 )
    0.0 ( 47.14 )
        Constipation,Week 97,n=4,5,3
    0.0 ( 0.00 )
    0.0 ( 0.00 )
    -22.2 ( 50.92 )
        Constipation,Week 115,n=2,6,3
    0.0 ( 0.00 )
    -5.6 ( 13.61 )
    -22.2 ( 50.92 )
        Constipation,Week 133,n=2,1,2
    0.0 ( 0.00 )
    0.0 ( 77777 )
    -50.0 ( 23.57 )
        Constipation,Week 151,n=0,2,0
    99999 ( 99999 )
    0.0 ( 0.00 )
    99999 ( 99999 )
        Constipation,Week 169,n=0,1,0
    99999 ( 99999 )
    0.0 ( 77777 )
    99999 ( 99999 )
        Constipation,Week 186,n=41,46,17
    5.7 ( 20.95 )
    3.6 ( 20.16 )
    3.9 ( 33.09 )
        Diarrhoea,Week 07,n=48,47,17
    -2.8 ( 26.48 )
    -0.0 ( 28.66 )
    -2.0 ( 24.92 )
        Diarrhoea,Week 13,n=29,29,16
    0.0 ( 25.20 )
    -6.9 ( 18.64 )
    4.2 ( 31.91 )
        Diarrhoea,Week 19,n=19,27,10
    1.8 ( 26.00 )
    -2.5 ( 24.33 )
    -3.3 ( 18.92 )
        Diarrhoea,Week 25,n=20,23,7
    3.3 ( 28.41 )
    -7.2 ( 33.27 )
    -19.0 ( 17.82 )
        Diarrhoea,Week 31,n=15,18,7
    -2.2 ( 23.46 )
    -3.7 ( 34.09 )
    -4.8 ( 29.99 )
        Diarrhoea,Week 37,n=15,13,5
    -2.2 ( 23.46 )
    2.6 ( 28.74 )
    -20.0 ( 18.26 )
        Diarrhoea,Week 43,n=15,14,4
    -4.4 ( 21.33 )
    14.3 ( 28.39 )
    -16.7 ( 19.25 )
        Diarrhoea,Week 61,n=11,11,3
    0.0 ( 21.08 )
    15.2 ( 31.14 )
    0.0 ( 33.33 )
        Diarrhoea,Week 79,n=3,2,2
    0.0 ( 0.00 )
    0.0 ( 0.00 )
    0.0 ( 47.14 )
        Diarrhoea,Week 97,n=4,5,3
    -8.3 ( 16.67 )
    0.0 ( 0.00 )
    -22.2 ( 19.25 )
        Diarrhoea,Week 115,n=2,6,3
    0.0 ( 0.00 )
    0.0 ( 0.00 )
    -22.2 ( 19.25 )
        Diarrhoea,Week 133,n=2,1,2
    0.0 ( 0.00 )
    0.0 ( 77777 )
    -33.3 ( 0.00 )
        Diarrhoea,Week 151,n=0,2,0
    99999 ( 99999 )
    0.0 ( 0.00 )
    99999 ( 99999 )
        Diarrhoea,Week 169,n=0,1,0
    99999 ( 99999 )
    0.0 ( 77777 )
    99999 ( 99999 )
        Diarrhoea,Week 186,n=41,46,17
    -0.8 ( 21.72 )
    -5.1 ( 28.08 )
    0.0 ( 35.36 )
        FD,Week 07,n=48,47,17
    -4.9 ( 25.72 )
    2.8 ( 24.90 )
    0.0 ( 16.67 )
        FD,Week 13,n=29,29,16
    -4.6 ( 23.10 )
    4.6 ( 19.36 )
    10.4 ( 20.07 )
        FD,Week 19,n=19,27,10
    -7.0 ( 21.02 )
    3.7 ( 26.69 )
    10.0 ( 22.50 )
        FD,Week 25,n=20,23,7
    -3.3 ( 26.27 )
    -1.4 ( 15.82 )
    0.0 ( 19.25 )
        FD,Week 31,n=15,18, 7
    -6.7 ( 22.54 )
    -1.9 ( 17.98 )
    4.8 ( 23.00 )
        FD,Week 37,n=15,13,5
    -2.2 ( 23.46 )
    -2.6 ( 16.45 )
    6.7 ( 14.91 )
        FD,Week 43,n=15,14,4
    -6.7 ( 18.69 )
    0.0 ( 22.65 )
    8.3 ( 31.91 )
        FD,Week 61,n=11,11,3
    -12.1 ( 37.34 )
    6.1 ( 29.13 )
    11.1 ( 19.25 )
        FD,Week 79,n=3,2,1
    0.0 ( 0.00 )
    -16.7 ( 23.57 )
    0.0 ( 77777 )
        FD,Week 97,n=4,5,3
    -25.0 ( 31.91 )
    0.0 ( 23.57 )
    -11.1 ( 19.25 )
        FD,Week 115,n=2,6,3
    0.0 ( 0.00 )
    22.2 ( 50.18 )
    -11.1 ( 19.25 )
        FD,Week 133,n=2,1,2
    -50.0 ( 23.57 )
    -33.3 ( 77777 )
    -16.7 ( 23.57 )
        FD,Week 151,n=0,2,0
    99999 ( 99999 )
    -33.3 ( 0.00 )
    99999 ( 99999 )
        FD,Week 169,n=0,1,0
    99999 ( 99999 )
    -33.3 ( 77777 )
    99999 ( 99999 )
        FD,Week 186,n=41,46,17
    -1.6 ( 24.67 )
    12.3 ( 25.68 )
    5.9 ( 21.20 )
    Notes
    [183] - Full Analysis Population
    [184] - Full Analysis Population
    [185] - Full Analysis Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in EORTC QLQ 20-item multiple myeloma module (MY20) score

    		 Close Top of page
    End point title
    		 Change from Baseline in EORTC QLQ 20-item multiple myeloma module (MY20) score
    End point description
    The EORTC QLQ-MY20 is supplement to QLQ-C30 instrument used in participants with multiple myeloma.The module comprised :20 questions that addressed four myeloma-specific HRQoL domains:disease symptoms(DS),side effects of treatment(SET),future perspective(FP) & body image(BI).Responses are 1 to 4.Scores were averaged & scales were transformed to 0 to100 scale.A high score for disease symptoms & side effects of treatment represented high level of symptomatology or problems,whereas high score for future perspective& body image represented better outcomes Baseline was defined as latest pre-dose assessment (Day 1) withnon-missing value, including unscheduled visits.Change from Baseline was calculated by subtracting Baseline value from post-dose visit value.99999 indicatesdata is not available.77777 indicates SD could not be calculated forsingle participant.Only those participants with data available at specified data points were analyzed(represented by n=X in the category titles).
    End point type
    Secondary
    End point timeframe
    Baseline (Day 1) and Week 07, Week 13, Week 19, Week 25, Week 31, Week 37, Week 43, Week 61, Week 79, Week 97, Week 115, Week 133, Week 151, Week 169, and Week 186
    End point values
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized)
    Number of subjects analysed
    97 [186]
    99 [187]
    25 [188]
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        FP,Week 07,n=47,45,16
    2.8 ( 25.11 )
    4.2 ( 29.99 )
    8.3 ( 24.51 )
        FP,Week 13,n=28,28,15
    -2.0 ( 24.39 )
    8.3 ( 22.55 )
    -2.2 ( 27.28 )
        FP,Week 19,n=18,25,10
    3.7 ( 22.87 )
    10.7 ( 20.91 )
    3.3 ( 27.24 )
        FP,Week 25,n=19,23,7
    2.3 ( 27.11 )
    13.5 ( 29.39 )
    4.8 ( 31.98 )
        FP,Week 31,n=14,18,7
    7.1 ( 18.80 )
    19.1 ( 24.93 )
    7.9 ( 27.00 )
        FP,Week 37,n=14,13,5
    6.3 ( 17.28 )
    29.1 ( 22.47 )
    11.1 ( 31.43 )
        FP,Week 43,n=15,13,4
    8.1 ( 21.19 )
    29.9 ( 26.98 )
    8.3 ( 5.56 )
        FP,Week 61,n=11,11,3
    10.1 ( 18.89 )
    4.0 ( 20.65 )
    25.9 ( 54.81 )
        FP,Week 79,n=3,2,2
    -7.4 ( 6.42 )
    33.3 ( 31.43 )
    38.9 ( 39.28 )
        FP,Week 97,n=4,5,3
    5.6 ( 14.34 )
    17.8 ( 39.75 )
    22.2 ( 40.06 )
        FP,Week 115,n=2,6,3
    11.1 ( 15.71 )
    16.7 ( 25.09 )
    33.3 ( 58.79 )
        FP,Week 133,n=2,1,2
    27.8 ( 7.86 )
    55.6 ( 77777 )
    38.9 ( 55.00 )
        FP,Week 151,n=0,2,0
    99999 ( 99999 )
    44.4 ( 15.71 )
    99999 ( 99999 )
        FP,Week 169,n=0,1,0
    99999 ( 99999 )
    55.6 ( 77777 )
    99999 ( 99999 )
        FP,Week 186,n=39,46,16
    -9.4 ( 19.34 )
    -7.7 ( 26.69 )
    3.5 ( 24.59 )
        BI,Week 07,n=47,45,16
    2.8 ( 22.87 )
    9.6 ( 28.09 )
    4.2 ( 43.67 )
        BI,Week 13,n=28,28,15
    6.0 ( 25.75 )
    6.0 ( 35.20 )
    -4.4 ( 37.52 )
        BI,Week 19,n=18,25,10
    5.6 ( 23.57 )
    8.0 ( 25.96 )
    -3.3 ( 42.89 )
        BI,Week 25,n=19,23,7
    7.0 ( 23.78 )
    15.9 ( 31.57 )
    9.5 ( 53.45 )
        BI,Week 31,n=14,18,7
    2.4 ( 20.52 )
    14.8 ( 30.73 )
    9.5 ( 56.81 )
        BI,Week 37,n=14,13,5
    9.5 ( 27.51 )
    25.6 ( 30.89 )
    26.7 ( 54.77 )
        BI,Week 43,n=15,13,4
    4.4 ( 24.77 )
    28.2 ( 38.12 )
    8.3 ( 16.67 )
        BI,Week 61,n=11,11,3
    6.1 ( 25.03 )
    12.1 ( 26.97 )
    33.3 ( 57.74 )
        BI,Week 79,n=3,2,2
    0.0 ( 0.00 )
    0.0 ( 0.00 )
    33.3 ( 94.28 )
        BI,Week 97,n=4,5,3
    8.3 ( 31.91 )
    6.7 ( 27.89 )
    44.4 ( 69.39 )
        BI,Week 115,n=2,6,3
    -16.7 ( 70.71 )
    5.6 ( 25.09 )
    55.6 ( 50.92 )
        BI,Week 133,n=2,1,2
    16.7 ( 23.57 )
    0.0 ( 77777 )
    83.3 ( 23.57 )
        BI,Week 151,n=0,2,0
    99999 ( 99999 )
    16.7 ( 23.57 )
    99999 ( 99999 )
        BI,Week 169,n=0,1,0
    99999 ( 99999 )
    0.0 ( 77777 )
    99999 ( 99999 )
        BI,Week 186,n=39,46,16
    -4.3 ( 30.76 )
    -0.7 ( 35.48 )
    10.4 ( 41.67 )
        DS,Week 07,n=47,45,16
    -1.8 ( 19.73 )
    -1.0 ( 17.78 )
    -2.8 ( 12.17 )
        DS,Week 13,n=28,28,15
    -1.0 ( 16.22 )
    -3.2 ( 22.95 )
    1.1 ( 25.65 )
        DS,Week 19,n=18,25,10
    0.9 ( 14.91 )
    -6.4 ( 17.98 )
    -1.7 ( 20.63 )
        DS,Week 25,n=19,23,7
    -0.0 ( 16.25 )
    -3.6 ( 17.78 )
    -1.6 ( 25.20 )
        DS,Week 31,n=14,18,7
    -3.6 ( 10.59 )
    -10.5 ( 19.23 )
    -4.8 ( 23.88 )
        DS,Week 37,n=14,13,5
    -6.0 ( 12.22 )
    -9.8 ( 22.92 )
    -14.4 ( 16.01 )
        DS,Week 43,n=15,13,4
    -5.9 ( 12.51 )
    -14.5 ( 24.06 )
    -8.3 ( 26.64 )
        DS,Week 61,n=11,11,3
    -11.6 ( 12.29 )
    -7.6 ( 10.02 )
    -11.1 ( 16.67 )
        DS,Week 79,n=3,2,2
    -16.7 ( 11.11 )
    -2.8 ( 3.93 )
    -2.8 ( 27.50 )
        DS,Week 97,n=4,5,3
    -12.5 ( 15.30 )
    -3.3 ( 15.52 )
    -7.4 ( 25.05 )
        DS,Week 115,n=2,6,3
    -19.4 ( 3.93 )
    -7.4 ( 10.92 )
    -10.0 ( 16.59 )
        DS,Week 133,n=2,1,2
    -13.9 ( 11.79 )
    -5.6 ( 77777 )
    8.3 ( 51.07 )
        DS,Week 151,n=0,2,0
    99999 ( 99999 )
    5.6 ( 15.71 )
    99999 ( 99999 )
        DS,Week 169,n=0,1,0
    99999 ( 99999 )
    -5.6 ( 77777 )
    99999 ( 99999 )
        DS,Week 186, n=39,46,16
    -0.6 ( 17.28 )
    2.5 ( 18.36 )
    4.9 ( 24.50 )
        SET,Week 07,n=47,45,16
    1.5 ( 9.21 )
    0.4 ( 13.33 )
    0.2 ( 15.49 )
        SET,Week 13,n=28,28,15
    2.0 ( 10.44 )
    -1.7 ( 11.96 )
    6.8 ( 23.69 )
        SET,Week 19,n=18,25,10
    0.0 ( 10.40 )
    -1.2 ( 10.87 )
    0.9 ( 9.04 )
        SET,Week 25,n=19,23,7
    3.4 ( 8.41 )
    0.1 ( 13.10 )
    0.4 ( 6.45 )
        SET,Week 31,n=14,18,7
    2.0 ( 6.07 )
    -2.9 ( 13.87 )
    5.5 ( 11.12 )
        SET,Week 37,n=14,13,5
    2.2 ( 6.91 )
    -6.0 ( 17.82 )
    -1.8 ( 4.04 )
        SET,Week 43,n=15,13,4
    1.0 ( 8.81 )
    -5.6 ( 19.05 )
    -4.9 ( 5.76 )
        SET,Week 61,n=11,11,3
    -2.1 ( 12.32 )
    1.9 ( 12.82 )
    2.0 ( 9.84 )
        SET,Week 79,n=3,2,2
    5.9 ( 11.40 )
    9.1 ( 12.83 )
    -1.3 ( 4.45 )
        SET,Week 97,n=4,5,3
    -0.2 ( 5.42 )
    5.0 ( 13.80 )
    -4.7 ( 3.44 )
        SET,Week 115,n=2,6,3
    5.7 ( 13.36 )
    0.7 ( 7.21 )
    -1.0 ( 7.09 )
        SET,Week 133,n=2,1,2
    5.7 ( 13.36 )
    -7.4 ( 77777 )
    -8.1 ( 5.24 )
        SET,Week 151,n=0,2,0
    99999 ( 99999 )
    0.0 ( 15.71 )
    99999 ( 99999 )
        SET,Week 169,n=0,1,0
    99999 ( 99999 )
    -11.1 ( 77777 )
    99999 ( 99999 )
        SET,Week 186,n=39,46,16
    4.0 ( 10.98 )
    4.0 ( 12.61 )
    3.7 ( 10.75 )
    Notes
    [186] - Full Analysis Population.
    [187] - Full Analysis Population.
    [188] - Full Analysis Population.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All-cause mortality, Serious adverse events (SAEs) and (>=5%) non-serious AEs (Non SAEs) were collected from the start of study treatment until maximum of 186 weeks
    Adverse event reporting additional description
    SAEs &non-SAEs reported for FSP (who received atleast 1 dose of frozen liquid or lyophilized powder).3 out of 221 participants did not receive drug &SAEs& non-SAEs were not reported.Deaths is reported for FSP(221)[all randomized whether or not randomized treatment was given].The results presented are based on data cut-off date 04 May 2022
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    GSK2857916 2.5 mg/kg (Frozen liquid)
    Reporting group description
    		 Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 2.5 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of up to 39 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.

    Reporting group title
    GSK2857916 3.4 mg/kg (Lyophilized)
    Reporting group description
    		 Participants were administered lyophilized powder (100 mg/vial in a single use vial) at a dose of 3.4 mg/kg GSK2857916 given IV for a maximum of up to 35 cycles (1 cycle= 21 days). Lyophilized powder was reconstituted using water for injection.

    Reporting group title
    GSK2857916 3.4 mg/kg (Frozen liquid)
    Reporting group description
    		 Participants were administered frozen liquid (30 mg/vial solution in a single use vial) at a dose of 3.4 mg/kg GSK2857916 as IV solution once every three weeks for a maximum of up to 32 cycles (1 cycle= 21 days). Frozen liquid was diluted with 0.9 percent saline.

    Serious adverse events
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized) GSK2857916 3.4 mg/kg (Frozen liquid)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    43 / 95 (45.26%)
    15 / 24 (62.50%)
    53 / 99 (53.54%)
         number of deaths (all causes)
    70
    16
    80
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Basal cell carcinoma
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 24 (4.17%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metastases to meninges
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 24 (4.17%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Haematoma
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 24 (4.17%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aortic stenosis
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    7 / 95 (7.37%)
    0 / 24 (0.00%)
    5 / 99 (5.05%)
         occurrences causally related to treatment / all
    2 / 8
    0 / 0
    5 / 7
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    2 / 99 (2.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 24 (4.17%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza like illness
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Haemophagocytic lymphohistiocytosis
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    2 / 95 (2.11%)
    1 / 24 (4.17%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    2 / 99 (2.02%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cough
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Delirium
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Electrocardiogram T wave inversion
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    3 / 95 (3.16%)
    0 / 24 (0.00%)
    2 / 99 (2.02%)
         occurrences causally related to treatment / all
    4 / 4
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal compression fracture
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 24 (4.17%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fracture
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper limb fracture
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 24 (4.17%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Cardiac arrest
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Atrial fibrillation
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 24 (4.17%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mitral valve disease
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericarditis
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pericardial effusion
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 24 (4.17%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral haemorrhage
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    3 / 99 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    1 / 3
    Cognitive disorder
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 24 (4.17%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lethargy
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Posterior reversible encephalopathy syndrome
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal cord compression
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 24 (4.17%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    1 / 95 (1.05%)
    3 / 24 (12.50%)
    3 / 99 (3.03%)
         occurrences causally related to treatment / all
    2 / 2
    2 / 3
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperviscosity syndrome
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    2 / 99 (2.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    3 / 99 (3.03%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    3 / 99 (3.03%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Keratopathy
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 24 (4.17%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ulcerative keratitis
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Gastrointestinal haemorrhage
         subjects affected / exposed
    2 / 95 (2.11%)
    0 / 24 (0.00%)
    2 / 99 (2.02%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ascites
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastric fibrosis
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematochezia
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestinal obstruction
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 24 (4.17%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Large intestinal haemorrhage
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 24 (4.17%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 24 (4.17%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intestinal haemorrhage
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stone
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 24 (4.17%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholestasis
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    2 / 95 (2.11%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary retention
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteolysis
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    2 / 99 (2.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Muscular weakness
         subjects affected / exposed
    1 / 95 (1.05%)
    1 / 24 (4.17%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pathological fracture
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthritis
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 24 (4.17%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Haematoma muscle
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 24 (4.17%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteonecrosis of jaw
         subjects affected / exposed
    1 / 95 (1.05%)
    1 / 24 (4.17%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Spinal osteoarthritis
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Sepsis
         subjects affected / exposed
    2 / 95 (2.11%)
    0 / 24 (0.00%)
    2 / 99 (2.02%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    7 / 95 (7.37%)
    1 / 24 (4.17%)
    14 / 99 (14.14%)
         occurrences causally related to treatment / all
    2 / 8
    0 / 1
    6 / 16
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 2
    Escherichia urinary tract infection
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    2 / 99 (2.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    2 / 99 (2.02%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    2 / 95 (2.11%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    2 / 99 (2.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular device infection
         subjects affected / exposed
    2 / 95 (2.11%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    2 / 99 (2.02%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia influenzal
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 24 (4.17%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Brain abscess
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis infectious
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Escherichia sepsis
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes simplex pneumonia
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia respiratory syncytial viral
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia legionella
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nocardiosis
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sinusitis
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Staphylococcal infection
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Staphylococcal bacteraemia
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Epiglottitis
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infective keratitis
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 95 (0.00%)
    0 / 24 (0.00%)
    1 / 99 (1.01%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypercalcaemia
         subjects affected / exposed
    4 / 95 (4.21%)
    1 / 24 (4.17%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    0 / 95 (0.00%)
    2 / 24 (8.33%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyponatraemia
         subjects affected / exposed
    1 / 95 (1.05%)
    1 / 24 (4.17%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    2 / 95 (2.11%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 24 (4.17%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypophosphataemia
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypomagnesaemia
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypocalcaemia
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    0 / 99 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 GSK2857916 2.5 mg/kg (Frozen liquid) GSK2857916 3.4 mg/kg (Lyophilized) GSK2857916 3.4 mg/kg (Frozen liquid)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    93 / 95 (97.89%)
    24 / 24 (100.00%)
    96 / 99 (96.97%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    9 / 95 (9.47%)
    2 / 24 (8.33%)
    10 / 99 (10.10%)
         occurrences all number
    10
    6
    11
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    15 / 95 (15.79%)
    12 / 24 (50.00%)
    28 / 99 (28.28%)
         occurrences all number
    19
    13
    37
    Pyrexia
         subjects affected / exposed
    18 / 95 (18.95%)
    4 / 24 (16.67%)
    22 / 99 (22.22%)
         occurrences all number
    21
    6
    29
    Asthenia
         subjects affected / exposed
    3 / 95 (3.16%)
    2 / 24 (8.33%)
    11 / 99 (11.11%)
         occurrences all number
    3
    2
    11
    Chills
         subjects affected / exposed
    8 / 95 (8.42%)
    2 / 24 (8.33%)
    4 / 99 (4.04%)
         occurrences all number
    8
    2
    4
    Oedema peripheral
         subjects affected / exposed
    5 / 95 (5.26%)
    3 / 24 (12.50%)
    4 / 99 (4.04%)
         occurrences all number
    5
    5
    10
    Pain
         subjects affected / exposed
    5 / 95 (5.26%)
    0 / 24 (0.00%)
    4 / 99 (4.04%)
         occurrences all number
    5
    0
    4
    Chest pain
         subjects affected / exposed
    2 / 95 (2.11%)
    3 / 24 (12.50%)
    2 / 99 (2.02%)
         occurrences all number
    2
    3
    2
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    9 / 95 (9.47%)
    1 / 24 (4.17%)
    17 / 99 (17.17%)
         occurrences all number
    11
    1
    21
    Cough
         subjects affected / exposed
    10 / 95 (10.53%)
    3 / 24 (12.50%)
    19 / 99 (19.19%)
         occurrences all number
    11
    4
    20
    Dyspnoea
         subjects affected / exposed
    8 / 95 (8.42%)
    3 / 24 (12.50%)
    6 / 99 (6.06%)
         occurrences all number
    8
    3
    7
    Oropharyngeal pain
         subjects affected / exposed
    1 / 95 (1.05%)
    1 / 24 (4.17%)
    5 / 99 (5.05%)
         occurrences all number
    1
    1
    5
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    6 / 95 (6.32%)
    2 / 24 (8.33%)
    1 / 99 (1.01%)
         occurrences all number
    6
    2
    1
    Depression
         subjects affected / exposed
    5 / 95 (5.26%)
    0 / 24 (0.00%)
    2 / 99 (2.02%)
         occurrences all number
    5
    0
    3
    Confusional state
         subjects affected / exposed
    0 / 95 (0.00%)
    1 / 24 (4.17%)
    5 / 99 (5.05%)
         occurrences all number
    0
    1
    6
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    21 / 95 (22.11%)
    6 / 24 (25.00%)
    24 / 99 (24.24%)
         occurrences all number
    26
    8
    30
    Blood creatinine increased
         subjects affected / exposed
    10 / 95 (10.53%)
    2 / 24 (8.33%)
    11 / 99 (11.11%)
         occurrences all number
    11
    2
    14
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    10 / 95 (10.53%)
    2 / 24 (8.33%)
    14 / 99 (14.14%)
         occurrences all number
    10
    2
    14
    Lymphocyte count decreased
         subjects affected / exposed
    13 / 95 (13.68%)
    2 / 24 (8.33%)
    10 / 99 (10.10%)
         occurrences all number
    15
    3
    13
    Blood alkaline phosphatase increased
         subjects affected / exposed
    9 / 95 (9.47%)
    1 / 24 (4.17%)
    11 / 99 (11.11%)
         occurrences all number
    10
    1
    11
    Platelet count decreased
         subjects affected / exposed
    15 / 95 (15.79%)
    3 / 24 (12.50%)
    11 / 99 (11.11%)
         occurrences all number
    18
    3
    26
    Neutrophil count decreased
         subjects affected / exposed
    7 / 95 (7.37%)
    2 / 24 (8.33%)
    11 / 99 (11.11%)
         occurrences all number
    10
    2
    13
    White blood cell count decreased
         subjects affected / exposed
    7 / 95 (7.37%)
    0 / 24 (0.00%)
    9 / 99 (9.09%)
         occurrences all number
    8
    0
    11
    Intraocular pressure increased
         subjects affected / exposed
    6 / 95 (6.32%)
    5 / 24 (20.83%)
    8 / 99 (8.08%)
         occurrences all number
    10
    6
    8
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    4 / 95 (4.21%)
    4 / 24 (16.67%)
    7 / 99 (7.07%)
         occurrences all number
    5
    4
    8
    Weight decreased
         subjects affected / exposed
    8 / 95 (8.42%)
    1 / 24 (4.17%)
    2 / 99 (2.02%)
         occurrences all number
    8
    1
    2
    Alanine aminotransferase increased
         subjects affected / exposed
    6 / 95 (6.32%)
    0 / 24 (0.00%)
    4 / 99 (4.04%)
         occurrences all number
    6
    0
    5
    Urine albumin/creatinine ratio increased
         subjects affected / exposed
    2 / 95 (2.11%)
    0 / 24 (0.00%)
    8 / 99 (8.08%)
         occurrences all number
    2
    0
    8
    C-reactive protein increased
         subjects affected / exposed
    3 / 95 (3.16%)
    1 / 24 (4.17%)
    5 / 99 (5.05%)
         occurrences all number
    3
    1
    5
    Blood creatine phosphokinase increased
         subjects affected / exposed
    5 / 95 (5.26%)
    0 / 24 (0.00%)
    3 / 99 (3.03%)
         occurrences all number
    13
    0
    3
    Bacterial test positive
         subjects affected / exposed
    0 / 95 (0.00%)
    2 / 24 (8.33%)
    0 / 99 (0.00%)
         occurrences all number
    0
    2
    0
    Blood bilirubin increased
         subjects affected / exposed
    1 / 95 (1.05%)
    2 / 24 (8.33%)
    1 / 99 (1.01%)
         occurrences all number
    1
    2
    2
    Injury, poisoning and procedural complications
    Infusion related reaction
         subjects affected / exposed
    15 / 95 (15.79%)
    2 / 24 (8.33%)
    9 / 99 (9.09%)
         occurrences all number
    16
    2
    10
    Contusion
         subjects affected / exposed
    0 / 95 (0.00%)
    2 / 24 (8.33%)
    8 / 99 (8.08%)
         occurrences all number
    0
    2
    8
    Rib fracture
         subjects affected / exposed
    1 / 95 (1.05%)
    2 / 24 (8.33%)
    2 / 99 (2.02%)
         occurrences all number
    1
    2
    2
    Fall
         subjects affected / exposed
    3 / 95 (3.16%)
    2 / 24 (8.33%)
    0 / 99 (0.00%)
         occurrences all number
    4
    2
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    11 / 95 (11.58%)
    5 / 24 (20.83%)
    17 / 99 (17.17%)
         occurrences all number
    12
    6
    22
    Dizziness
         subjects affected / exposed
    1 / 95 (1.05%)
    1 / 24 (4.17%)
    7 / 99 (7.07%)
         occurrences all number
    1
    1
    8
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    25 / 95 (26.32%)
    8 / 24 (33.33%)
    36 / 99 (36.36%)
         occurrences all number
    28
    14
    49
    Thrombocytopenia
         subjects affected / exposed
    22 / 95 (23.16%)
    8 / 24 (33.33%)
    44 / 99 (44.44%)
         occurrences all number
    34
    12
    73
    Neutropenia
         subjects affected / exposed
    7 / 95 (7.37%)
    1 / 24 (4.17%)
    18 / 99 (18.18%)
         occurrences all number
    17
    4
    27
    Leukopenia
         subjects affected / exposed
    9 / 95 (9.47%)
    0 / 24 (0.00%)
    7 / 99 (7.07%)
         occurrences all number
    9
    0
    8
    Lymphopenia
         subjects affected / exposed
    6 / 95 (6.32%)
    1 / 24 (4.17%)
    5 / 99 (5.05%)
         occurrences all number
    6
    1
    5
    Eye disorders
    Vision blurred
         subjects affected / exposed
    22 / 95 (23.16%)
    8 / 24 (33.33%)
    30 / 99 (30.30%)
         occurrences all number
    37
    13
    50
    Keratopathy
         subjects affected / exposed
    67 / 95 (70.53%)
    23 / 24 (95.83%)
    74 / 99 (74.75%)
         occurrences all number
    267
    100
    320
    Dry eye
         subjects affected / exposed
    14 / 95 (14.74%)
    5 / 24 (20.83%)
    19 / 99 (19.19%)
         occurrences all number
    18
    10
    21
    Photophobia
         subjects affected / exposed
    7 / 95 (7.37%)
    3 / 24 (12.50%)
    9 / 99 (9.09%)
         occurrences all number
    12
    3
    16
    Diplopia
         subjects affected / exposed
    2 / 95 (2.11%)
    2 / 24 (8.33%)
    4 / 99 (4.04%)
         occurrences all number
    3
    2
    5
    Eye pruritus
         subjects affected / exposed
    2 / 95 (2.11%)
    1 / 24 (4.17%)
    5 / 99 (5.05%)
         occurrences all number
    2
    1
    10
    Blepharitis
         subjects affected / exposed
    2 / 95 (2.11%)
    0 / 24 (0.00%)
    6 / 99 (6.06%)
         occurrences all number
    3
    0
    6
    Visual acuity reduced
         subjects affected / exposed
    5 / 95 (5.26%)
    3 / 24 (12.50%)
    5 / 99 (5.05%)
         occurrences all number
    8
    3
    5
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    24 / 95 (25.26%)
    2 / 24 (8.33%)
    32 / 99 (32.32%)
         occurrences all number
    29
    3
    40
    Constipation
         subjects affected / exposed
    12 / 95 (12.63%)
    4 / 24 (16.67%)
    9 / 99 (9.09%)
         occurrences all number
    13
    5
    9
    Vomiting
         subjects affected / exposed
    8 / 95 (8.42%)
    0 / 24 (0.00%)
    21 / 99 (21.21%)
         occurrences all number
    11
    0
    23
    Diarrhoea
         subjects affected / exposed
    11 / 95 (11.58%)
    4 / 24 (16.67%)
    15 / 99 (15.15%)
         occurrences all number
    14
    4
    15
    Skin and subcutaneous tissue disorders
    Hyperhidrosis
         subjects affected / exposed
    3 / 95 (3.16%)
    2 / 24 (8.33%)
    2 / 99 (2.02%)
         occurrences all number
    3
    2
    2
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    5 / 95 (5.26%)
    3 / 24 (12.50%)
    3 / 99 (3.03%)
         occurrences all number
    11
    3
    21
    Haematuria
         subjects affected / exposed
    2 / 95 (2.11%)
    2 / 24 (8.33%)
    1 / 99 (1.01%)
         occurrences all number
    8
    2
    1
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    12 / 95 (12.63%)
    6 / 24 (25.00%)
    12 / 99 (12.12%)
         occurrences all number
    13
    6
    12
    Arthralgia
         subjects affected / exposed
    19 / 95 (20.00%)
    4 / 24 (16.67%)
    16 / 99 (16.16%)
         occurrences all number
    24
    6
    19
    Pain in extremity
         subjects affected / exposed
    8 / 95 (8.42%)
    1 / 24 (4.17%)
    12 / 99 (12.12%)
         occurrences all number
    8
    1
    16
    Bone pain
         subjects affected / exposed
    4 / 95 (4.21%)
    0 / 24 (0.00%)
    9 / 99 (9.09%)
         occurrences all number
    5
    0
    10
    Musculoskeletal chest pain
         subjects affected / exposed
    7 / 95 (7.37%)
    1 / 24 (4.17%)
    7 / 99 (7.07%)
         occurrences all number
    7
    1
    9
    Myalgia
         subjects affected / exposed
    2 / 95 (2.11%)
    2 / 24 (8.33%)
    4 / 99 (4.04%)
         occurrences all number
    2
    2
    5
    Muscular weakness
         subjects affected / exposed
    2 / 95 (2.11%)
    0 / 24 (0.00%)
    6 / 99 (6.06%)
         occurrences all number
    2
    0
    6
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    10 / 95 (10.53%)
    4 / 24 (16.67%)
    20 / 99 (20.20%)
         occurrences all number
    12
    4
    24
    Urinary tract infection
         subjects affected / exposed
    6 / 95 (6.32%)
    1 / 24 (4.17%)
    9 / 99 (9.09%)
         occurrences all number
    7
    1
    16
    Bronchitis
         subjects affected / exposed
    6 / 95 (6.32%)
    0 / 24 (0.00%)
    2 / 99 (2.02%)
         occurrences all number
    6
    0
    2
    Nasopharyngitis
         subjects affected / exposed
    1 / 95 (1.05%)
    0 / 24 (0.00%)
    5 / 99 (5.05%)
         occurrences all number
    1
    0
    6
    Pneumonia
         subjects affected / exposed
    2 / 95 (2.11%)
    2 / 24 (8.33%)
    5 / 99 (5.05%)
         occurrences all number
    2
    2
    5
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    12 / 95 (12.63%)
    5 / 24 (20.83%)
    19 / 99 (19.19%)
         occurrences all number
    16
    5
    21
    Hypokalaemia
         subjects affected / exposed
    5 / 95 (5.26%)
    3 / 24 (12.50%)
    12 / 99 (12.12%)
         occurrences all number
    5
    7
    13
    Hypercalcaemia
         subjects affected / exposed
    10 / 95 (10.53%)
    4 / 24 (16.67%)
    15 / 99 (15.15%)
         occurrences all number
    11
    5
    17
    Hyponatraemia
         subjects affected / exposed
    5 / 95 (5.26%)
    4 / 24 (16.67%)
    12 / 99 (12.12%)
         occurrences all number
    6
    4
    14
    Hyperuricaemia
         subjects affected / exposed
    9 / 95 (9.47%)
    1 / 24 (4.17%)
    7 / 99 (7.07%)
         occurrences all number
    23
    1
    7
    Hypoalbuminaemia
         subjects affected / exposed
    4 / 95 (4.21%)
    1 / 24 (4.17%)
    8 / 99 (8.08%)
         occurrences all number
    4
    1
    12
    Hypophosphataemia
         subjects affected / exposed
    7 / 95 (7.37%)
    3 / 24 (12.50%)
    8 / 99 (8.08%)
         occurrences all number
    10
    3
    11
    Hypomagnesaemia
         subjects affected / exposed
    5 / 95 (5.26%)
    1 / 24 (4.17%)
    6 / 99 (6.06%)
         occurrences all number
    7
    1
    8
    Hypocalcaemia
         subjects affected / exposed
    4 / 95 (4.21%)
    2 / 24 (8.33%)
    3 / 99 (3.03%)
         occurrences all number
    4
    2
    3
    Hyperglycaemia
         subjects affected / exposed
    5 / 95 (5.26%)
    3 / 24 (12.50%)
    7 / 99 (7.07%)
         occurrences all number
    9
    4
    11

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 Apr 2018
    Amendment 01: Addressed regulatory agency advice. The original single-arm design with 1 dose level (3.4 milligram per kilogram [mg/kg] GSK2857916 once every 3 weeks [Q3W]) was amended to an open label, randomized, 2-arm study with 2 dose levels by including the 2.5 mg/kg Q3W dose. In addition, a new exploratory cohort of 25 participants, who will receive a lyophilized configuration of GSK2857916, was added to gain clinical experience with the lyophilized configuration. To accommodate these main changes, the overall sample size and related analytical methods were changed.
    04 Sep 2018
    Amendment 02: Addressed feedback from regulatory agencies, ethics commitee/institutional review board, and investigators. The updates included the addition of Exclusion Criteria defining the use of high dose steroids, clarification of specific timeframe from last treatment required for systemic anti-myeloma therapy, and increase of corrected QT interval Fridericia criteria. Additional pharmacokinetic sampling timepoints were added to capture the maximum observed concentration of the free cytotoxic drug (cysteine-maleimidocaproyl monomethyl auristatin F [cys-mcMMAF]) and to better define the kinetics of cys-mcMMAF and the elimination phase of antibody drug conjugate and cys-mcMMAF. Soluble B-cell maturation antigen (BCMA) collection timepoints were also added to capture the effect of GSK2857916 administration on soluble BCMA concentrations over time as a marker of pharmacodynamic effect. The dose modifications guidelines for GSK2857916 related Corneal Events clarified dose adjustments for GlaxoSmithKline Scale Grade 2 events.
    17 Dec 2018
    Amendment 03: Addressed over-enrolment in the frozen liquid solution portion of the study. Due to the over-enrolment, the primary analysis will be based on all randomized participants (anticipated approximately 200) enroled into the frozen liquid solution arms. In addition, a sensitivity analysis based on the first 130 participants will be performed to account for the original design.
    21 Oct 2019
    Amendment 04: Updated schedule of activities to include the footnotes. Updated risk assessment, modified dose justification, modified treatments administered, updated dose reductions for toxicity, modified corneal supportive care guidelines and schedule of activities, updated guidance on prohibited medications, updated requirements for efficacy assessments, modified timeframes for contraception usage in males and females, modified monocular prophylaxis and treatment, updated immunogenicity, updated timeframe of minimal residual disease testing, updated GlaxoSmithKline corneal event severity scale and mitigation strategy for treatment related corneal events.
    08 Oct 2020
    Amendment 05:The protocol has been amended to provide updates based on analyses of data from the DREAMM-1, DREAMM-2 and the exposure Corrected QT interval. The updates include the removal of ECG collection, unless clinically indicated, and updated contraception timeframe. The dose modification guidelines for belantamab mafodotin related corneal events was updated to align with the approved label and an appendix on Home Healthcare and Telemedicine Approaches was introduced as a result of the COVID-19 pandemic to ensure sites and participants had alternate approaches to assist participants to continue receiving care while maintaining protocol adherence.
    19 Nov 2021
    Amendment 06: The protocol has been amended to provide updates including the addition of the end of study definition and continued access to study intervention after the end of the study section (Post Analysis Continued Treatment [PACT])

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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