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    Clinical Trial Results:
    An open-label, single-arm, multi-center phase 2 trial with ofatumumab in patients with relapsed/progressive Diffuse Large B-Cell Lymphoma (DLBCL) ineligible for transplant or relapsed/progression after autologous transplant

    Summary
    EudraCT number
    		 2007-004190-26
    Trial protocol
    		 BE   DK   GB   FR   ES   IT  
    Global end of trial date
    18 Aug 2014

    Results information
    Results version number
    		 v1(current)
    This version publication date
    13 Apr 2016
    First version publication date
    07 Mar 2015
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    GEN415
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    13 Oct 2014
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Aug 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To investigate the efficacy of ofatumumab in patients with relapsed/progressive DLBCL ineligible for transplant or relapsed/progression after autologous transplant
    Protection of trial subjects
    Not applicable
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    13 Dec 2007
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Efficacy
    Long term follow-up duration
    		 60 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    United Kingdom: 24
    Country: Number of subjects enrolled
    Belgium: 23
    Country: Number of subjects enrolled
    Denmark: 2
    Country: Number of subjects enrolled
    Spain: 3
    Country: Number of subjects enrolled
    France: 14
    Country: Number of subjects enrolled
    Italy: 7
    Country: Number of subjects enrolled
    Romania: 4
    Country: Number of subjects enrolled
    United States: 4
    Worldwide total number of subjects
    81
    EEA total number of subjects
    77
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    31
    From 65 to 84 years
    49
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 This was an open-label, single-arm, multi-center phase II trial. During the treatment phase, participants (par.) received 8 weekly infusions of ofatumumab (first infusion of 300 mg followed by 7 infusions of 1000 mg).

    Period 1
    Period 1 title
    Overall study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Ofatumumab
    Arm description
    		 Participants received 8 weekly intravenous (iv) infusions of ofatumumab: first infusion of 300 milligrams (mg), followed by 7 infusions of 1000 mg
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ofatumumab
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Concentrate for solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Treatment administration: Participants were given ofatumumab by intravenous infusion as follows: First infusion of 300 mg, followed by seven weekly infusions of 1000 mg. Pre-medication with oral paracetamol 1000 mg (or equivalent) and cetirizine 10 mg (or equivalent) before every infusion and glucocorticoid equivalent to 100 mg prednisolone before infusions 1 and 2 was administered 30 minutes to 2 hours prior to treatment with ofatumumab.

    Investigational medicinal product name
    Paracetamol
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Film-coated tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Pre-medication with oral paracetamol 1000 mg (or equivalent) before every infusion.

    Investigational medicinal product name
    Cetirizine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Pre-medication with oral cetirizine 10 mg (or equivalent) before every infusion.

    Investigational medicinal product name
    Glucocorticoid
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Pre-medication with oral glucocorticoid equivalent to 100 mg prednisolone before infusions 1 and 2 was administered 30 minutes to 2 hours prior to treatment with ofatumumab.

    Number of subjects in period 1
    		Ofatumumab
    Started
    81
    Completed
    9
    Not completed
    72
         Consent withdrawn by subject
    1
         Received Alternate Anticancer Therapy
    8
         Adverse event, non-fatal
    6
         Death
    3
         Participant Refusal
    1
         Took Prohibited Medication
    2
         Insurance Expired
    1
         Disease Progression
    47
         Protocol deviation
    3

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Ofatumumab
    Reporting group description
    		 Participants received 8 weekly intravenous (iv) infusions of ofatumumab: first infusion of 300 milligrams (mg), followed by 7 infusions of 1000 mg

    Reporting group values
    		 Ofatumumab Total
    Number of subjects
    		 81 81
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 64.9 ( 14.51 ) -
    Gender categorical
    Units: Subjects
        Female
    		 36 36
        Male
    		 45 45
    Race
    Units: Subjects
        Asian
    		 2 2
        Hispanic or Latino
    		 2 2
        White
    		 76 76
        Missing
    		 1 1
    Number of Participants with the Indicated Prior Therapy
    Study participants had to have either prior autologous stem cell transplant (ASCT) or had to be ineligible for ASCT to be eligible for inclusion.
    Units: Subjects
        Prior ASCT
    		 25 25
        Ineligible for ASCT
    		 56 56

    End points

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    End points reporting groups
    Reporting group title
    Ofatumumab
    Reporting group description
    		 Participants received 8 weekly intravenous (iv) infusions of ofatumumab: first infusion of 300 milligrams (mg), followed by 7 infusions of 1000 mg

    Primary: Number of participants with objective response

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    End point title
    		 Number of participants with objective response [1]
    End point description
    Objective response of ofatumumab treatment was assessed according to the “revised response criteria for malignant lymphoma.” Participants with objective response were defined as responders with complete remission (CR) or partial remission (PR) of disease. CR is defined as the disappearance of all evidence of disease, and PR is defined as the regression of measurable disease with no new sites of disease. Full Analysis Set (FAS): all participants who were exposed to study drug irrespective of their compliance to the planned course of treatment. Response rate is calculated as the number of responses divided by the number of par. treated, expressed as a percentage. Objective response: Estimated value = 11%, 2-sided 95% CI=5% to 20%. The exact (Clopper-Pearson) method was used to calculate the confidence interval (CI).
    End point type
    Primary
    End point timeframe
    6-month period from start of treatment (up to Week 24)
    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: Statistical information is entered in the endpoint description. The system does not allow statistical data to be entered in the statisticial analysis section for studies with 1 treatment arm.
    End point values
    		 Ofatumumab
    Number of subjects analysed
    81 [2]
    Units: Participants
    9
    Notes
    [2] - FAS
    No statistical analyses for this end point

    Primary: Number of participants classified as responders and non-responders for objective response

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    End point title
    		 Number of participants classified as responders and non-responders for objective response [3]
    End point description
    According to the "revised response criteria for malignant lymphoma," responders included par. with CR and PR, and non-responders included par. with stable disease (SD) and progressive disease (PD). Par. not evaluable (NE) were also considered to be non-responders. PD is defined as any new lesion or an increase by more than or equal to 50% of previously involved sites from baseline. SD is defined as failure to attain CR, PR, or PD. Response rate is calculated as the number of responses divided by the number of par. treated, expressed as a percentage. Responders with CR: Estimated value = 2%, 2-sided 95% CI=0% to 9%. Responders with PR: Estimated value = 9%, 2-sided 95% CI=4% to 17%. Non-responders with SD: Estimated value = 17%, 2-sided 95% CI=10% to 27%. Non-responders with PD: Estimated value = 42%, 2-sided 95% CI=31% to 53%. Non-responders with NE: Estimated value = 30%, 2-sided 95% CI=20% to 41%. The exact (Clopper-Pearson) method was used to calculate the CI.
    End point type
    Primary
    End point timeframe
    6-month period from start of treatment (up to Week 24)
    Notes
    [3] - 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: Statistical information is entered in the endpoint description. The system does not allow statistical data to be entered in the statisticial analysis section for studies with 1 treatment arm.
    End point values
    		 Ofatumumab
    Number of subjects analysed
    81 [4]
    Units: Participants
        Responders with CR
    2
        Responders with PR
    7
        Non-responders with SD
    14
        Non-responders with PD
    34
        Non-responders with NE
    24
    Notes
    [4] - FAS
    No statistical analyses for this end point

    Secondary: Duration of response

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    End point title
    		 Duration of response
    End point description
    The duration of response was defined as the time from the initial response (CR or PR) to the time of relapse, progression, or death. If the participant was lost to follow-up, the endpoint was censored, and the censoring date was the date of the last attended visit at which the endpoint was assessed. The upper limit of the 95% confidence interval could not be determined (not reached) because too few participants experienced the event; therefore, the value of 99999 was entered which represents NA.
    End point type
    Secondary
    End point timeframe
    From date of start of treatment to 2 years or withdrawal
    End point values
    		 Ofatumumab
    Number of subjects analysed
    9 [5]
    Units: Months
        median (confidence interval 95%)
    9.5 (5.4 to 99999)
    Notes
    [5] - FAS. Only participants with CR or PR were analyzed.
    No statistical analyses for this end point

    Secondary: Progression-free survival (PFS)

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    End point title
    		 Progression-free survival (PFS)
    End point description
    PFS was defined as the time from treatment start until progression or death.
    End point type
    Secondary
    End point timeframe
    From date of start of treatment to 2 years or withdrawal
    End point values
    		 Ofatumumab
    Number of subjects analysed
    81 [6]
    Units: Months
        median (confidence interval 95%)
    2.5 (2.3 to 4.9)
    Notes
    [6] - FAS
    No statistical analyses for this end point

    Secondary: Time to next Diffuse Large B-Cell Lymphoma (DLBCL) therapy

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    End point title
    		 Time to next Diffuse Large B-Cell Lymphoma (DLBCL) therapy
    End point description
    Time to next DLBCL therapy was defined as the time from the first infusion date to the time of the first administration of the next DLBCL treatment other than ofatumumab. If the participants were lost to follow-up, the endpoint was censored, and the censoring date was the date of the last attended visit at which the endpoint was assessed. The median and the upper limit of the 95% confidence interval could not be determined (not reached) because too few participants experienced the event; therefore, the value of 99999 was entered which represents NA.
    End point type
    Secondary
    End point timeframe
    From date of start of treatment to 5 years or withdrawal
    End point values
    		 Ofatumumab
    Number of subjects analysed
    81 [7]
    Units: Months
        median (confidence interval 95%)
    99999 (7.4 to 99999)
    Notes
    [7] - FAS
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

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    End point title
    		 Overall Survival (OS)
    End point description
    Overall survival is defined as the time from first infusion to death. Overall survival was a secondary endpoint in the study. However, since many participants withdrew from the study after developing disease progression overall survival could not be reliably estimated.
    End point type
    Secondary
    End point timeframe
    From date of start of treatment to 5 years or withdrawal
    End point values
    		 Ofatumumab
    Number of subjects analysed
    0 [8]
    Units: Months
        median (standard deviation)
    ( )
    Notes
    [8] - FAS
    No statistical analyses for this end point

    Secondary: Number of participants with positive human anti-human antibodies (HAHA) at Screening and at Visits 12, 13, 14, and 18

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    End point title
    		 Number of participants with positive human anti-human antibodies (HAHA) at Screening and at Visits 12, 13, 14, and 18
    End point description
    HAHA are indicators of immune response to ofatumumab. Blood samples were collected from participants at Visits 1, 12, 13, 14, and 18 and analyzed in batches. The number of participants with positive results at each visit is reported.
    End point type
    Secondary
    End point timeframe
    Screening visit (<= 14 days before treatment start), Visit 12 (Month 6), Visit 13 (Month 9), Visit 14 (Month 12), and Visit 18 (Month 24)
    End point values
    		 Ofatumumab
    Number of subjects analysed
    79 [9]
    Units: participants
        Screening, n=79
    0
        Visit 12 (Month 6), n=20
    0
        Visit 13, (Month 9), n=16
    0
        Visit 14 (Month 12), n=16
    0
        Visit 18 (Month 24), n=8
    0
    Notes
    [9] - FAS. Data are provided for the number of participants attending each visit.
    No statistical analyses for this end point

    Secondary: Median percent change from Baseline in CD45+CD19+ and CD45+CD20+ cells in the peripheral blood at the indicated visits

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    End point title
    		 Median percent change from Baseline in CD45+CD19+ and CD45+CD20+ cells in the peripheral blood at the indicated visits
    End point description
    B cells (CD45+CD19+ and CD45+CD20+) were measured in peripheral blood samples by flow cytometry. Percent change from Baseline = (value at the indicated visits minus the value at Baseline divided by the value at Baseline) * 100.
    End point type
    Secondary
    End point timeframe
    Baseline and Visit 10 (Week 8), Visit 11 (Week 11), Visit 12 (Month 6), Visit 13 (Month 9), Visit 14 (Month 12), Visit 15 (Month 15), Visit 16 (Month 18), Visit 17 (Month 21), Visit 18 (Month 24), Visit 19 (Month 30), Visit 20 (Month 36)
    End point values
    		 Ofatumumab
    Number of subjects analysed
    42 [10]
    Units: percent change in cells
    median (full range (min-max))
        CD45+CD19+, Visit 10 (Week 8), n=42
    -100 (-100 to 0)
        CD45+CD19+, Visit 11 (Week 11), n=29
    -100 (-100 to 56)
        CD45+CD19+, Visit 12 (Month 6), n=18
    -100 (-100 to 0)
        CD45+CD19+, Visit 13 (Month 9), n=15
    -100 (-100 to 0)
        CD45+CD19+, Visit 14 (Month 12), n=13
    -100 (-100 to 0)
        CD45+CD19+, Visit 15 (Month 15), n=12
    -60.7 (-100 to 12)
        CD45+CD19+, Visit 16 (Month 18), n=8
    6 (-88 to 179)
        CD45+CD19+, Visit 17 (Month 21), n=8
    -6.9 (-58 to 56)
        CD45+CD19+, Visit 18 (Month 24), n=5
    -11.1 (-100 to 50)
        CD45+CD19+, Visit 19 (Month 30), n=2
    80.8 (12 to 150)
        CD45+CD19+, Visit 20 (Month 36), n=2
    68.6 (-36 to 174)
        CD45+CD20+, Visit 10 (Week 8), n=42
    -100 (-100 to 0)
        CD45+CD20+, Visit 11 (Week 11), n=29
    -100 (-100 to 56)
        CD45+CD20+, Visit 12 (Month 6), n=18
    -100 (-100 to 0)
        CD45+CD20+, Visit 13 (Month 9), n=15
    -100 (-100 to 0)
        CD45+CD20+, Visit 14 (Month 12), n=13
    -100 (-100 to 0)
        CD45+CD20+, Visit 15 (Month 15), n=12
    -57.3 (-100 to 0)
        CD45+CD20+, Visit 16 (Month 18), n=8
    6 (-88 to 171)
        CD45+CD20+, Visit 17 (Month 21), n=8
    -6.9 (-58 to 28)
        CD45+CD20+, Visit 18 (Month 24), n=5
    -11.1 (-100 to 50)
        CD45+CD20+, Visit 19 (Month 30), n=2
    75.2 (7 to 143)
        CD45+CD20+, Visit 20 (Month 36), n=2
    68.6 (-36 to 174)
    Notes
    [10] - FAS. Data are provided for the number of participants attending each visit.
    No statistical analyses for this end point

    Secondary: Number of participants who experienced at least one adverse event (AE)

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    End point title
    		 Number of participants who experienced at least one adverse event (AE)
    End point description
    An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product that does not necessarily have a causal relationship with this treatment. The protocol-defined AE reporting period was from the first infusion (Visit 2/Week 0) to Visit 18 (Month 24 of follow-up) or time of withdrawal (treatment and follow-up).
    End point type
    Secondary
    End point timeframe
    From the date of start of treatment to 2 years or withdrawal
    End point values
    		 Ofatumumab
    Number of subjects analysed
    81 [11]
    Units: Participants
    78
    Notes
    [11] - FAS
    No statistical analyses for this end point

    Secondary: Percent change from Screening in complement (CH50) levels

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    End point title
    		 Percent change from Screening in complement (CH50) levels
    End point description
    CH50 was mistakenly registered as an outcome measure with the protocol record. Samples were not collected, and no analysis will take place. Thus, no data will be reported for this outcome measure.
    End point type
    Secondary
    End point timeframe
    Screening and post-baseline visits (last visit was to occur 24 months post first dose)
    End point values
    		 Ofatumumab
    Number of subjects analysed
    0 [12]
    Units: percent change in complement levels
    Notes
    [12] - FAS
    No statistical analyses for this end point

    Secondary: AUC(0-inf) and AUC(0-168) for ofatumumab at the eighth infusion

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    End point title
    		 AUC(0-inf) and AUC(0-168) for ofatumumab at the eighth infusion
    End point description
    AUC is defined as the area under the ofatumumab concentration-time curve as a measure of drug exposure. AUC(0-168) is the AUC from the start of infusion to 168 hours after the start of the infusion; AUC(0-inf) is the AUC from the start of infusion extrapolated to infinity. Data are provided for the number of participants attending each visit for whom the parameter value could be calculated. Participants contributing AUC(0-inf) data also contributed AUC(0-168) data.
    End point type
    Secondary
    End point timeframe
    Visit 9 (Week 7; up to 11 months after last dose)
    End point values
    		 Ofatumumab
    Number of subjects analysed
    46 [13]
    Units: micrograms*hour/milliliter (µg.h/mL)
    geometric mean (geometric coefficient of variation)
        AUC(0-inf), n=30
    720388 ( 79 )
        AUC(0-168), n=46
    110193 ( 27 )
    Notes
    [13] - FAS
    No statistical analyses for this end point

    Secondary: Cmax and Ctrough for ofatumumab at the first and eighth infusions

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    End point title
    		 Cmax and Ctrough for ofatumumab at the first and eighth infusions
    End point description
    Cmax is defined as the maximum concentration of drug in serum samples. Ctrough is defined as the minimum observed concentration prior to the start of the next dose. No drug is present prior to the first infusion; therefore, there are no Ctrough results for the first dose.
    End point type
    Secondary
    End point timeframe
    Visit 2 (Week 0) and Visit 9 (Week 7)
    End point values
    		 Ofatumumab
    Number of subjects analysed
    74 [14]
    Units: micrograms per milliliter (µg/mL)
    geometric mean (geometric coefficient of variation)
        First infusion Cmax; 300 mg, n=74
    109 ( 42 )
        Eighth infusion Cmax; 1000 mg, n=48
    839 ( 24 )
        Eighth infusion Ctrough; 1000 mg, n=48
    497 ( 34 )
    Notes
    [14] - FAS. Data are provided for the number of participants attending each visit.
    No statistical analyses for this end point

    Secondary: Half-life (T1/2) for ofatumumab at the eigth infusion

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    End point title
    		 Half-life (T1/2) for ofatumumab at the eigth infusion
    End point description
    t1/2 is defined as terminal half-life and is the time required for the amount of drug in the body to decrease by half. Data are provided for the number of participants at each visit for whom the parameter could be calculated.
    End point type
    Secondary
    End point timeframe
    Visit 9 (Week 7; up to 11 months after last dose)
    End point values
    		 Ofatumumab
    Number of subjects analysed
    30 [15]
    Units: Hours
        geometric mean (geometric coefficient of variation)
    637 ( 51 )
    Notes
    [15] - FAS
    No statistical analyses for this end point

    Secondary: Clearance (CL) of ofatumumab at the eighth infusion

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    End point title
    		 Clearance (CL) of ofatumumab at the eighth infusion
    End point description
    CL is the clearance of drug from serum, which is defined as the volume of serum from which the drug is cleared per unit time. Data are presented for the number of participants at each visit for whom the parameter can be calculated.
    End point type
    Secondary
    End point timeframe
    Visit 9 (Week 7; up to 11 months after last dose)
    End point values
    		 Ofatumumab
    Number of subjects analysed
    46 [16]
    Units: milliliters per hour (mL/h)
        geometric mean (geometric coefficient of variation)
    9.1 ( 28 )
    Notes
    [16] - FAS
    No statistical analyses for this end point

    Secondary: Volume of distribution at steady state (Vss) of ofatumumab at the eighth infusion

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    End point title
    		 Volume of distribution at steady state (Vss) of ofatumumab at the eighth infusion
    End point description
    Vss is the volume of distribution at steady state of ofatumumab. Data are presented for the number of participants attending each visit for whom the parameter can be calculated.
    End point type
    Secondary
    End point timeframe
    Visit 9 (Week 7; up to 11 months after the last dose)
    End point values
    		 Ofatumumab
    Number of subjects analysed
    30 [17]
    Units: liters
        geometric mean (geometric coefficient of variation)
    8.3 ( 45 )
    Notes
    [17] - FAS
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events (AE) were reported from first infusion (Week 0) to Month 24 of follow-up (FU)/withdrawal (treatment and FU). Serious AEs were reported through Month 60 (treatment, FU, and extended FU).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    15.1
    Reporting groups
    Reporting group title
    Ofatumumab
    Reporting group description
    		 Participants received 8 weekly iv infusions of ofatumumab: first infusion of 300 mg, followed by 7 infusions of 1000 mg

    Serious adverse events
    		 Ofatumumab
    Total subjects affected by serious adverse events
         subjects affected / exposed
    37 / 81 (45.68%)
         number of deaths (all causes)
    8
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Non-Hodgkin's lymphoma
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    General disorders and administration site conditions
    Disease progression
         subjects affected / exposed
    8 / 81 (9.88%)
         occurrences causally related to treatment / all
    0 / 8
         deaths causally related to treatment / all
    0 / 5
    Pyrexia
         subjects affected / exposed
    2 / 81 (2.47%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    Multi-organ failure
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Oedema peripheral
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pleuritic pain
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Haemoglobin decreased
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Injury, poisoning and procedural complications
    Femur fracture
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Humerus fracture
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bradycardia
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Cardiac failure
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nervous system disorders
    Neurological symptom
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Paraparesis
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    3 / 81 (3.70%)
         occurrences causally related to treatment / all
    2 / 4
         deaths causally related to treatment / all
    0 / 0
    Neutropenia
         subjects affected / exposed
    2 / 81 (2.47%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    2 / 81 (2.47%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Anaemia
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Leukopenia
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Eye disorders
    Eyelid ptosis
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    Cholangitis acute
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatitis acute
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Renal and urinary disorders
    Renal failure
         subjects affected / exposed
    2 / 81 (2.47%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Pneumonia
         subjects affected / exposed
    2 / 81 (2.47%)
         occurrences causally related to treatment / all
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Central line infection
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Sepsis
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    1 / 81 (1.23%)
         occurrences causally related to treatment / all
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Ofatumumab
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    70 / 81 (86.42%)
    Vascular disorders
    Hypotension
         subjects affected / exposed
    4 / 81 (4.94%)
         occurrences all number
    5
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    13 / 81 (16.05%)
         occurrences all number
    15
    Oedema peripheral
         subjects affected / exposed
    13 / 81 (16.05%)
         occurrences all number
    15
    Pyrexia
         subjects affected / exposed
    8 / 81 (9.88%)
         occurrences all number
    8
    Asthenia
         subjects affected / exposed
    6 / 81 (7.41%)
         occurrences all number
    7
    Non-cardiac chest pain
         subjects affected / exposed
    3 / 81 (3.70%)
         occurrences all number
    9
    Infusion related reaction
         subjects affected / exposed
    2 / 81 (2.47%)
         occurrences all number
    3
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    6 / 81 (7.41%)
         occurrences all number
    7
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    8 / 81 (9.88%)
         occurrences all number
    11
    Dyspnoea
         subjects affected / exposed
    7 / 81 (8.64%)
         occurrences all number
    8
    Pharyngolaryngeal pain
         subjects affected / exposed
    4 / 81 (4.94%)
         occurrences all number
    5
    Rales
         subjects affected / exposed
    4 / 81 (4.94%)
         occurrences all number
    4
    Pleural effusion
         subjects affected / exposed
    3 / 81 (3.70%)
         occurrences all number
    3
    Throat irritation
         subjects affected / exposed
    3 / 81 (3.70%)
         occurrences all number
    4
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    4 / 81 (4.94%)
         occurrences all number
    4
    Investigations
    Blood creatinine increased
         subjects affected / exposed
    5 / 81 (6.17%)
         occurrences all number
    6
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    3 / 81 (3.70%)
         occurrences all number
    4
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    3 / 81 (3.70%)
         occurrences all number
    3
    Nervous system disorders
    Headache
         subjects affected / exposed
    5 / 81 (6.17%)
         occurrences all number
    7
    Dizziness
         subjects affected / exposed
    4 / 81 (4.94%)
         occurrences all number
    6
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    10 / 81 (12.35%)
         occurrences all number
    12
    Anaemia
         subjects affected / exposed
    9 / 81 (11.11%)
         occurrences all number
    11
    Leukopenia
         subjects affected / exposed
    9 / 81 (11.11%)
         occurrences all number
    10
    Lymphopenia
         subjects affected / exposed
    7 / 81 (8.64%)
         occurrences all number
    7
    Thrombocytopenia
         subjects affected / exposed
    5 / 81 (6.17%)
         occurrences all number
    5
    Eye disorders
    Conjunctivitis
         subjects affected / exposed
    4 / 81 (4.94%)
         occurrences all number
    4
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    15 / 81 (18.52%)
         occurrences all number
    15
    Abdominal pain
         subjects affected / exposed
    11 / 81 (13.58%)
         occurrences all number
    12
    Constipation
         subjects affected / exposed
    11 / 81 (13.58%)
         occurrences all number
    13
    Nausea
         subjects affected / exposed
    10 / 81 (12.35%)
         occurrences all number
    12
    Vomiting
         subjects affected / exposed
    6 / 81 (7.41%)
         occurrences all number
    6
    Abdominal pain upper
         subjects affected / exposed
    5 / 81 (6.17%)
         occurrences all number
    5
    Stomatitis
         subjects affected / exposed
    4 / 81 (4.94%)
         occurrences all number
    4
    Dry mouth
         subjects affected / exposed
    3 / 81 (3.70%)
         occurrences all number
    3
    Dyspepsia
         subjects affected / exposed
    3 / 81 (3.70%)
         occurrences all number
    3
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    7 / 81 (8.64%)
         occurrences all number
    8
    Pruritus
         subjects affected / exposed
    6 / 81 (7.41%)
         occurrences all number
    6
    Urticaria
         subjects affected / exposed
    4 / 81 (4.94%)
         occurrences all number
    5
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    5 / 81 (6.17%)
         occurrences all number
    5
    Muscle spasms
         subjects affected / exposed
    4 / 81 (4.94%)
         occurrences all number
    4
    Arthralgia
         subjects affected / exposed
    2 / 81 (2.47%)
         occurrences all number
    2
    Neck pain
         subjects affected / exposed
    2 / 81 (2.47%)
         occurrences all number
    2
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    6 / 81 (7.41%)
         occurrences all number
    7
    Nasopharyngitis
         subjects affected / exposed
    5 / 81 (6.17%)
         occurrences all number
    8
    Herpes zoster
         subjects affected / exposed
    4 / 81 (4.94%)
         occurrences all number
    4
    Metabolism and nutrition disorders
    Anorexia
         subjects affected / exposed
    8 / 81 (9.88%)
         occurrences all number
    8

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 Jun 2007
    Amendment No.: 01 Update the protocol with changes in accordance with the transfer of sponsorship of the trial Gen415 from Genmab A/S to GlaxoSmithKine (GSK)as of 28 April 2008.
    18 Jul 2008
    Amendment No.: 02 Clarify and elaborate on inclusion criteria no. 1. In the same connection exclusion criteria 15 and the section on pre-medicaton will be updated due to errors.

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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