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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	v3(current)
This version publication date	01 Jan 2024
First version publication date	26 Apr 2020
Other versions	v1 , v2
Version creation reason	New data added to full data set NIH comments addressal

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

205678

ISRCTN number

US NCT number

WHO universal trial number (UTN)

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

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

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?

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

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

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

127

85 years and over

Subject disposition

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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).

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 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

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

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.

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
Consent withdrawn by subject	8	2	2
Physician decision	2	4	-
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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Reporting group title

GSK2857916 2.5 mg/kg (Frozen liquid)

Reporting group description

Reporting group title

GSK2857916 3.4 mg/kg (Frozen liquid)

Reporting group description

Reporting group title

GSK2857916 3.4 mg/kg (Lyophilized)

Reporting group description

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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Reporting group title

GSK2857916 2.5 mg/kg (Frozen liquid)

Reporting group description

Reporting group title

GSK2857916 3.4 mg/kg (Frozen liquid)

Reporting group description

Reporting group title

GSK2857916 3.4 mg/kg (Lyophilized)

Reporting group description

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: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

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 by investigator assessment (Efficacy Population)

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End point title

Clinical benefit rate by investigator assessment (Efficacy Population) ^[12]

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
[12] - 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: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	GSK2857916 2.5 mg/kg (Frozen liquid)	GSK2857916 3.4 mg/kg (Frozen liquid)
Number of subjects analysed	64 ^[13]	66 ^[14]
Units: Percentage of Participants
number (confidence interval 95%)	34 (22.9 to 47.3)	35 (23.5 to 47.6)

Notes
[13] - Efficacy Population.
[14] - Efficacy 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

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: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

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 (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 ^[18]	99 ^[19]	25 ^[20]
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
[18] - Full Analysis Population
[19] - Full Analysis Population
[20] - Full Analysis 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 ^[21]	32 ^[22]	13 ^[23]
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
[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: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

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: 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

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 ^[27]	99 ^[28]	25 ^[29]
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
[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: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

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: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

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: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

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 (Efficacy Population)

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End point title

Time to response by Independent Review Committee (Efficacy Population) ^[45]

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
[45] - 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: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

End point values	GSK2857916 2.5 mg/kg (Frozen liquid)	GSK2857916 3.4 mg/kg (Frozen liquid)
Number of subjects analysed	20 ^[46]	20 ^[47]
Units: Months
median (inter-quartile range (Q1-Q3))	1.5 (0.8 to 2.5)	1.4 (1.1 to 1.9)

Notes
[46] - Efficacy Population.
[47] - 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 ^[48]	99 ^[49]	25 ^[50]
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
[48] - Full Analysis Population
[49] - Full Analysis Population
[50] - Full Analysis Population

No statistical analyses for this end point

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

Top of page

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 ^[51]	35 ^[52]	13 ^[53]
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
[51] - Full Analysis Population.
[52] - Full Analysis Population.
[53] - 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 ^[54]	99 ^[55]	25 ^[56]
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
[54] - Full Analysis Population
[55] - Full Analysis Population
[56] - 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 ^[57]	99 ^[58]	25 ^[59]
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
[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

Top of page

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: 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 ^[63]	99 ^[64]	24 ^[65]
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
[63] - Full Safety Population.
[64] - Full Safety Population.
[65] - Full Safety 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 ^[66]	99 ^[67]	25 ^[68]
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
[66] - Full Analysis Population
[67] - Full Analysis Population
[68] - Full Analysis 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 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 ^[87]	99 ^[88]	24 ^[89]
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
[87] - Full Safety Population
[88] - Full Safety Population
[89] - 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)

Top of page

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 ^[90]	99 ^[91]	24 ^[92]
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
[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 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 ^[99]	93 ^[100]	23 ^[101]
Units: Participants
Right eye,n=95,93,23	0	4	0
Left eye,n=93,92,22	0	2	0

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 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 ^[102]	90 ^[103]	23 ^[104]
Units: Participants	4	12	3

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 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 ^[105]	94 ^[106]	24 ^[107]
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
[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: 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 ^[111]	99 ^[112]	24 ^[113]
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
[111] - Full PK Population
[112] - Full PK Population
[113] - Full PK 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 ^[114]	31 ^[115]	2 ^[116]
Units: Participants
Left eye,n=34,30,2	14	12	2
Right eye,n=30,31,2	11	12	1

Notes
[114] - Full Safety Population.
[115] - Full Safety Population.
[116] - Full Safety 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 ^[117]	99 ^[118]	24 ^[119]
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
[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 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

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=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
[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

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

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: 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

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
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
[129] - Full PK Population
[130] - Full PK Population
[131] - 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 ^[132]	99 ^[133]	24 ^[134]
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
[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

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

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: 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

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: 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
[141] - Full PK Population
[142] - Full PK Population
[143] - 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 ^[144]	99 ^[145]	24 ^[146]
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
[144] - Full PK Population
[145] - Full PK Population
[146] - 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 ^[147]	99 ^[148]	24 ^[149]
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
[147] - Full PK Population
[148] - Full PK Population
[149] - 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

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
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
[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: 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 ^[156]	99 ^[157]	24 ^[158]
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
[156] - Full PK Population
[157] - Full PK Population
[158] - 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 ^[159]	99 ^[160]	24 ^[161]
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
[159] - Full PK Population
[160] - Full PK Population
[161] - 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 ^[162]	99 ^[163]	24 ^[164]
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
[162] - Full PK Population
[163] - Full PK Population
[164] - 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 ^[165]	99 ^[166]	24 ^[167]
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
[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: This endpoint is only reporting on a subset of the arms that are contained in the Baseline period.

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/QoLbetter functioning ability or healthrelated quality-of-life(HRQoL),whereas high score for symptom scales/single items-significant symptomatology.Baseline was latest predose assessment with non-missing value,including unscheduled visits.Change from Baseline was post-dose visit minus Baseline value.Only those participants who were measured analyzed(i.e.contributed data reported in the table)were included in the Overall Number of Participants Analyzed field.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

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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 modulecomprised 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 latest pre-dose assessment (Day 1) withnon-missing value, including unscheduled visits.Change from Baseline was 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 who were measured analyzed(i.e.,contributed data reported in the table)were included in the Overall Number of Participants Analyzed field.

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

Top of page

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 name

MedDRA

Dictionary version

24.1

Reporting group title

GSK2857916 2.5 mg/kg (Frozen liquid)

Reporting group description

Reporting group title

GSK2857916 3.4 mg/kg (Lyophilized)

Reporting group description

Reporting group title

GSK2857916 3.4 mg/kg (Frozen liquid)

Reporting group description

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
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
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
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
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
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
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
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
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

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Were there any global substantial amendments to the protocol? Yes

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])

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Secondary: Progression free survival by investigator assessment

Secondary: Progression free survival by investigator assessment

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

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

Secondary: Progression free survival by Independent Review Committee

Secondary: Progression free survival by Independent Review Committee

Secondary: Time to progression by investigator assessment

Secondary: Time to progression by investigator assessment

Secondary: Time to progression by Independent Review Committee

Secondary: Time to progression by Independent Review Committee

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

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

Secondary: Overall survival

Secondary: Overall survival

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

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

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

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

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

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

Secondary: Number of participants with abnormal findings during physical examination

Secondary: Number of participants with abnormal findings during physical examination

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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)

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)

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