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    Clinical Trial Results:
    An Open Label, Multicenter Study Investigating the Safety and Efficacy of Ofatumumab Therapy versus Physicians' Choice in Patients with Bulky Fludarabine Refractory Chronic Lymphocytic Leukemia (CLL) Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.novfor complete trial results.

    Summary
    EudraCT number
    		 2010-023066-52
    Trial protocol
    		 SE   GB   HU   FR   IE   CZ   DE   SK   AT   IT   BE  
    Global end of trial date
    24 Apr 2017

    Results information
    Results version number
    		 v1(current)
    This version publication date
    27 Oct 2018
    First version publication date
    27 Oct 2018
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    COMB157A2302/114242
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01313689
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Pharma, AG
    Sponsor organisation address
    CH-4002, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma, AG, 41 613241111, novartis.email@novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma, AG, 41 613241111, novartis.email@novartis.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    24 Apr 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    24 Apr 2017
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To evaluate improvement in progression-free survival (PFS), defined as the time from randomization to the date of disease progression or death due to any cause, in patients with bulky fludarabine refractory (BFR) CLL receiving ofatumumab (OFA) compared to physicians’ choice (PC) of treatment.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    14 Apr 2011
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Bulgaria: 4
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Germany: 11
    Country: Number of subjects enrolled
    Hungary: 12
    Country: Number of subjects enrolled
    Israel: 2
    Country: Number of subjects enrolled
    Italy: 6
    Country: Number of subjects enrolled
    Poland: 10
    Country: Number of subjects enrolled
    Russian Federation: 14
    Country: Number of subjects enrolled
    Singapore: 1
    Country: Number of subjects enrolled
    Slovakia: 5
    Country: Number of subjects enrolled
    Sweden: 14
    Country: Number of subjects enrolled
    Ukraine: 26
    Country: Number of subjects enrolled
    United Kingdom: 5
    Country: Number of subjects enrolled
    Austria: 9
    Worldwide total number of subjects
    122
    EEA total number of subjects
    79
    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)
    70
    From 65 to 84 years
    52
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Note: The 'Total Participants' in the Baseline Characteristics Table and in most of the Efficacy results Tables should be either Any OFA + Physician’s Choice or OFA extended + OFA observation + OFA + Physician’s Choice instead of the automatic calculated Total number indicated.

    Pre-assignment
    Screening details
    		 Participants(par) were randomized to receive an Open-Label treatment(trt) of ofatumumab(OFA) or a physicians choice(PC) trt for up to 24 weeks. OFA par without progressive disease(PD) underwent a second randomization to receive an additional 24 weeks of OFA or no further trt. PC par who developed PD had the option to receive OFA salvage therapy.

    Period 1
    Period 1 title
    24-Week Randomization 1
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Any Ofatumumab
    Arm description
    		 Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ofatumumab
    Investigational medicinal product code
    OMB157
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    OFA was infused intravenously with an initial dose of 300 mg, followed 1 week later with 2000 mg once weekly for 7 weeks, followed 4 weeks later by one infusion of 2000 mg every 4 weeks for 4 infusions, for a total of 12 infusions over 24 weeks.

    Arm title
    		 Physician's Choice (PC)
    Arm description
    		 Par. randomized to receive PC trt during Randomization 1 were admin. treatments approved for Chronic Lymphocytic Leukaemia (CLL) & well-established standards of care as prescribed with standard dose & route. Experimental therapies or any doses beyond approved/standard of care dose ranges were not allowed. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for max. trt duration of 48 weeks. Par. entered Follow-up after OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status & anti-cancer therapy information was collected in the SFU. Par. did not receive OFA salvage trt & demonstrated PD, entered SFU.Of 43 par 22 went to OFA salvage arm.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Various PC therapies that were approved for CLL at the time of the study
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    PC therapies were infused intravenously with an initial dose of 300 mg, followed 1 week later with 2000 mg once weekly for 7 weeks, followed 4 weeks later by one infusion of 2000 mg every 4 weeks for 4 infusions, for a total of 12 infusions over 24 weeks.

    Number of subjects in period 1
    		Any Ofatumumab Physician's Choice (PC)
    Started
    79
    43
    Completed
    60
    33
    Not completed
    19
    10
         Physician decision
    4
    5
         Consent withdrawn by subject
    5
    -
         Adverse event, non-fatal
    10
    5
    Period 2
    Period 2 title
    24-Week Randomization 2
    Is this the baseline period?
    		 No
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Ofatumumab Extended (OFA Ext)
    Arm description
    		 Par. randomized to receive OFA at Randomization 1 and at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 continued to receive OFA 2000 mg IV every 4 weeks for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ofatumumab
    Investigational medicinal product code
    OMB157
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    OFA was infused intravenously with an initial dose of 300 mg, followed 1 week later with 2000 mg once weekly for 7 weeks, followed 4 weeks later by one infusion of 2000 mg every 4 weeks for 4 infusions, for a total of 12 infusions over 24 weeks.

    Arm title
    		 Ofatumumab Observation (OFA Observ.)
    Arm description
    		 Par. randomized to receive OFA at Randomization 1 and receiving no treatment at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 received no treatment for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or at end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ofatumumab
    Investigational medicinal product code
    OMB157
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    OFA was infused intravenously with an initial dose of 300 mg, followed 1 week later with 2000 mg once weekly for 7 weeks, followed 4 weeks later by one infusion of 2000 mg every 4 weeks for 4 infusions, for a total of 12 infusions over 24 weeks.

    Arm title
    		 OFA first Randomization Only (OFA FRO)
    Arm description
    		 Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. These participants were only randomized once and did not get make it to the second randomization. Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Ofatumumab
    Investigational medicinal product code
    OMB157
    Other name
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    OFA was infused intravenously with an initial dose of 300 mg, followed 1 week later with 2000 mg once weekly for 7 weeks, followed 4 weeks later by one infusion of 2000 mg every 4 weeks for 4 infusions, for a total of 12 infusions over 24 weeks.

    Number of subjects in period 2 [1]
    		Ofatumumab Extended (OFA Ext) Ofatumumab Observation (OFA Observ.) OFA first Randomization Only (OFA FRO)
    Started
    24
    13
    42
    Completed
    21
    12
    27
    Not completed
    3
    1
    15
         Consent withdrawn by subject
    1
    1
    3
         Physician decision
    -
    -
    4
         Adverse event, non-fatal
    2
    -
    8
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: This is correct as per results in CSR

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Any Ofatumumab
    Reporting group description
    		 Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Reporting group title
    Physician's Choice (PC)
    Reporting group description
    		 Par. randomized to receive PC trt during Randomization 1 were admin. treatments approved for Chronic Lymphocytic Leukaemia (CLL) & well-established standards of care as prescribed with standard dose & route. Experimental therapies or any doses beyond approved/standard of care dose ranges were not allowed. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for max. trt duration of 48 weeks. Par. entered Follow-up after OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status & anti-cancer therapy information was collected in the SFU. Par. did not receive OFA salvage trt & demonstrated PD, entered SFU.Of 43 par 22 went to OFA salvage arm.

    Reporting group values
    		 Any Ofatumumab Physician's Choice (PC) Total
    Number of subjects
    		 79 43 122
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 46 24 70
        From 65-84 years
    		 33 19 52
        85 years and over
    		 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 ( ) 61.8 ( 9.87 ) -
    Sex: Female, Male
    Units: Subjects
        Female
    		 14 14
        Male
    		 29 29
    Race/Ethnicity, Customized
    Units: Subjects
        Hispanic or Latino|
    		 0 0
        Not Hispanic or Latino|
    		 43 43
    Subject analysis sets

    Subject analysis set title
    Any Ofatumumab (OFA)
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Subject analysis set title
    Any Ofatumumab (OFA)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Subject analysis set title
    Any Ofatumumab (OFA)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Subject analysis set title
    Any Ofatumumab (OFA)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Subject analysis set title
    Any Ofatumumab (OFA)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Subject analysis set title
    Any Ofatumumab (OFA)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Subject analysis set title
    OFA Salvage
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The participants in this arm are from the Physician's Choice (PC) arm. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for the maximum trt duration of 48 weeks. Par. entered Follow-up after the OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Subject analysis set title
    Ofatumumab Extended (OFA Ext)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Par. randomized to receive OFA at Randomization 1 and at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 continued to receive OFA 2000 mg IV every 4 weeks for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Subject analysis set title
    Ofatumumab Observation (OFA Observ.)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Par. randomized to receive OFA at Randomization 1 and receiving no treatment at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 received no treatment for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or at end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Subject analysis set title
    OFA first Randomization Only (OFA FRO)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. These participants were only randomized once and did not get make it to the second randomization. Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Subject analysis sets values
    		 Any Ofatumumab (OFA) Any Ofatumumab (OFA) Any Ofatumumab (OFA) Any Ofatumumab (OFA) Any Ofatumumab (OFA) Any Ofatumumab (OFA) OFA Salvage Ofatumumab Extended (OFA Ext) Ofatumumab Observation (OFA Observ.) OFA first Randomization Only (OFA FRO)
    Number of subjects
    79
    56
    44
    30
    23
    78
    22
    24
    13
    42
    Age categorical
    Units: Subjects
        In utero
        Preterm newborn infants (gestational age < 37 wks)
        Newborns (0-27 days)
        Infants and toddlers (28 days-23 months)
        Children (2-11 years)
        Adolescents (12-17 years)
        Adults (18-64 years)
        From 65-84 years
        85 years and over
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    63.3 ( 8.95 )
    63.3 ( 8.95 )
    63.3 ( 8.95 )
    63.3 ( 8.95 )
    63.3 ( 8.95 )
    63.3 ( 8.95 )
    63.3 ( 8.95 )
    61.7 ( 9.09 )
    66.7 ( 5.99 )
    63.2 ( 9.52 )
    Sex: Female, Male
    Units: Subjects
        Female
    24
    9
    2
    13
        Male
    55
    15
    11
    29
    Race/Ethnicity, Customized
    Units: Subjects
        Hispanic or Latino|
    1
    0
    0
    1
        Not Hispanic or Latino|
    78
    24
    13
    41

    End points

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    End points reporting groups
    Reporting group title
    Any Ofatumumab
    Reporting group description
    		 Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Reporting group title
    Physician's Choice (PC)
    Reporting group description
    		 Par. randomized to receive PC trt during Randomization 1 were admin. treatments approved for Chronic Lymphocytic Leukaemia (CLL) & well-established standards of care as prescribed with standard dose & route. Experimental therapies or any doses beyond approved/standard of care dose ranges were not allowed. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for max. trt duration of 48 weeks. Par. entered Follow-up after OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status & anti-cancer therapy information was collected in the SFU. Par. did not receive OFA salvage trt & demonstrated PD, entered SFU.Of 43 par 22 went to OFA salvage arm.
    Reporting group title
    Ofatumumab Extended (OFA Ext)
    Reporting group description
    		 Par. randomized to receive OFA at Randomization 1 and at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 continued to receive OFA 2000 mg IV every 4 weeks for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Reporting group title
    Ofatumumab Observation (OFA Observ.)
    Reporting group description
    		 Par. randomized to receive OFA at Randomization 1 and receiving no treatment at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 received no treatment for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or at end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Reporting group title
    OFA first Randomization Only (OFA FRO)
    Reporting group description
    		 Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. These participants were only randomized once and did not get make it to the second randomization. Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Subject analysis set title
    Any Ofatumumab (OFA)
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Subject analysis set title
    Any Ofatumumab (OFA)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Subject analysis set title
    Any Ofatumumab (OFA)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Subject analysis set title
    Any Ofatumumab (OFA)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Subject analysis set title
    Any Ofatumumab (OFA)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Subject analysis set title
    Any Ofatumumab (OFA)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Following Randomization 1, par. not demonstrating PD entered Randomization 2 (OFA Extended or OFA Observation); or par. entered Survival Follow-up (SFU) if demonstrating progressive disease (PD). During Randomization 2, par. either received another 24 weeks of OFA 2000 mg every 4 weeks (OFA Extension) or received no further treatment (trt) (OFA Observation). Par. entered Follow-up until withdrawal or the end of study (60 months). Par only entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Subject analysis set title
    OFA Salvage
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    The participants in this arm are from the Physician's Choice (PC) arm. Par. who developed PD during PC trt or Follow-up had the option to receive (single-agent) OFA salvage trt. Par. received an initial IV dose of OFA 300 mg. One week later, par. received OFA 2000 mg followed by 7 weekly infusions of OFA 2000 mg, followed by infusions of OFA 2000 mg every 4 weeks until Week 48, for the maximum trt duration of 48 weeks. Par. entered Follow-up after the OFA salvage trt until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during OFA salvage trt. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Subject analysis set title
    Ofatumumab Extended (OFA Ext)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Par. randomized to receive OFA at Randomization 1 and at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 continued to receive OFA 2000 mg IV every 4 weeks for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or the end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Subject analysis set title
    Ofatumumab Observation (OFA Observ.)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Par. randomized to receive OFA at Randomization 1 and receiving no treatment at Randomization 2. Only the par. who did not demonstrate PD during the first 24 weeks of OFA therapy entered Randomization 2. At Randomization 1, par. were initially administered OFA 300 mg IV. Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. Par. randomized to Randomization 2 received no treatment for another 24 weeks. Par. entered Follow-up after the treatment period until withdrawal or at end of study (60 months). Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Subject analysis set title
    OFA first Randomization Only (OFA FRO)
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Participants (par.) were randomized to receive ofatumumab (OFA) at Randomization 1. Par. were initially administered OFA 300 milligrams (mg) intravenously (IV). Beginning at Week 2, par. were administered OFA 2000 mg once weekly for 7 weeks, followed by 4 infusions of OFA 2000 mg every 4 weeks for a total of 12 infusions over 24 weeks. These participants were only randomized once and did not get make it to the second randomization. Par. entered SFU if demonstrating PD during the study. Only the survival status and anti-cancer therapy information was collected in the SFU.

    Primary: Progression-free Survival (PFS) as assessed by Independent Review Committee (IRC)

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    End point title
    		 Progression-free Survival (PFS) as assessed by Independent Review Committee (IRC)
    End point description
    PFS is the interval of time between the date of first randomization to the date of disease progression (PD) or death due to any reason, whichever occurred first. The date of PD was defined as the first occurrence of any criteria of progression. PD criteria requires at least one of the following: progression of lymphadenopathy, >=50% increase in liver or spleen size, >=50% increase in number of lymphocytes per microliter, more aggressive histology, occurence of cytopenia after treatment attributable to CLL. Disease progression was determined according to the 2008 International Workshop for Chronic Lymphocytic Leukaemia (IWCLL) update of the National Cancer Institute-sponsored Working Group CLL Guidelines for Response (NCI-WG). PFS was censored at the time of the last follow up for participants who have neither progressed or died.
    End point type
    Primary
    End point timeframe
    From the randomization date up to 60 months post the randomization date.
    End point values
    		 Any Ofatumumab Physician's Choice (PC) Ofatumumab Extended (OFA Ext) Ofatumumab Observation (OFA Observ.)
    Number of subjects analysed
    79
    43
    24
    13
    Units: Months
        median (confidence interval 95%)
    5.36 (4.30 to 6.97)
    3.61 (1.87 to 6.74)
    10.05 (7.23 to 13.80)
    7.16 (5.36 to 9.49)
    Statistical analysis title
    		 Any OFA vs PC (IRC)
    Comparison groups
    Physician's Choice (PC) v Any Ofatumumab
    Number of subjects included in analysis
    122
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2677
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.79
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 1.24
    Statistical analysis title
    		 OFA Ext. vs OFA Observ.
    Comparison groups
    Ofatumumab Extended (OFA Ext) v Ofatumumab Observation (OFA Observ.)
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0837
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.19
         upper limit
    		 1.53

    Secondary: Progression-free Survival (PFS) as assessed by Investigator

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    End point title
    		 Progression-free Survival (PFS) as assessed by Investigator
    End point description
    PFS is the interval of time between the date of first randomization to the date of disease progression (PD) or death due to any reason, whichever occurred first. The date of PD was defined as the first occurrence of any criteria of progression. PD criteria requires at least one of the following: progression of lymphadenopathy, >=50% increase in liver or spleen size, >=50% increase in number of lymphocytes per microliter, more aggressive histology, occurence of cytopenia after treatment attributable to CLL. Disease progression was determined according to the 2008 International Workshop for Chronic Lymphocytic Leukaemia (IWCLL) update of the National Cancer Institute-sponsored Working Group CLL Guidelines for Response (NCI-WG). PFS was censored at the time of the last follow up for participants who have neither progressed or died.
    End point type
    Secondary
    End point timeframe
    From the randomization date up to 60 months post the randomization date.
    End point values
    		 Any Ofatumumab Physician's Choice (PC) Ofatumumab Extended (OFA Ext) Ofatumumab Observation (OFA Observ.)
    Number of subjects analysed
    79
    43
    24
    13
    Units: Months
        median (confidence interval 95%)
    7.00 (5.42 to 8.25)
    4.50 (1.97 to 5.62)
    12.68 (10.09 to 14.29)
    9.49 (7.00 to 12.12)
    Statistical analysis title
    		 OFA Ext vs OFA Observ (by Investigator)
    Comparison groups
    Ofatumumab Extended (OFA Ext) v Ofatumumab Observation (OFA Observ.)
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0262
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.49
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.21
         upper limit
    		 1.17
    Statistical analysis title
    		 Any OFA vs PC Choice (by Investigator)
    Comparison groups
    Physician's Choice (PC) v Any Ofatumumab
    Number of subjects included in analysis
    122
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.003
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.56
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.35
         upper limit
    		 0.87

    Secondary: Overall response rate (ORR) as assessed by the IRC

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    End point title
    		 Overall response rate (ORR) as assessed by the IRC
    End point description
    ORR is defined as the number of participants achieving either complete response (CR) or partial response (PR). ORR was measured using the IWCLL updated NCI-WG guidelines 2008. CR requires all of the following criteria: no lymphadenopathy(Ly)/ hepatomegaly, splenomegaly, constitutional symptoms; neutrophils >1500 per microliter(µL), platelets(PL) >100,000/µL, hemoglobin(Hb) >11 grams/deciliter(g/dL), lymphocytes(LC) <4000/µL, bone marrow(BM) sample must be normocellular for age, <30% LC and no lymphoid nodules. PR requires the following criteria for at least 2 months: >=50% decrease in LC, reduction in Ly (i.e., >=50% decrease in lymph node size or no increase or new lymph nodes), >=50% decrease in the size of liver and spleen and at least one of the following results: PL >100,000/µL or 50% improvement over Baseline(BL), Hb >11 g/dL or 50% improvement over BL, neutrophils>1500/μL. Nodular PR (nPR) indicates persistent nodules in the BM.
    End point type
    Secondary
    End point timeframe
    From the randomization date up to 60 months post the randomization date.
    End point values
    		 Any Ofatumumab Physician's Choice (PC) Ofatumumab Extended (OFA Ext) Ofatumumab Observation (OFA Observ.)
    Number of subjects analysed
    79
    43
    24
    13
    Units: Participants
        CR|
    0
    0
    0
    0
        PR|
    30
    7
    18
    8
        nPR|
    0
    0
    0
    0
        Stable Disease|
    36
    22
    5
    5
        Progressive Disease|
    9
    8
    1
    0
        Not Evaluable|
    4
    6
    0
    0
        Missing|
    0
    0
    0
    0
    Statistical analysis title
    		 ORR by IRC: Any OFA vs PC (ORR)
    Comparison groups
    Physician's Choice (PC) v Any Ofatumumab
    Number of subjects included in analysis
    122
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0223
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    2.942
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.166
         upper limit
    		 7.424
    Statistical analysis title
    		 ORR by IRC: OFA Ext. vs OFA Observ.
    Comparison groups
    Ofatumumab Extended (OFA Ext) v Ofatumumab Observation (OFA Observ.)
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9985
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    999.999
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.001
         upper limit
    		 999.999

    Secondary: Overall response rate (ORR) as assessed by the Investigator

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    End point title
    		 Overall response rate (ORR) as assessed by the Investigator
    End point description
    ORR is defined as the number of participants achieving either complete response (CR) or partial response (PR). Overall response was measured using the IWCLL updated NCI-WG guidelines 2008. CR requires all of the following criteria: no lymphadenopathy(Ly)/ hepatomegaly, splenomegaly, constitutional symptoms; neutrophils >1500 per microliter(µL), platelets(PL) >100,000/µL, hemoglobin(Hb) >11 grams/deciliter(g/dL), lymphocytes(LC) <4000/µL, bone marrow(BM) sample must be normocellular for age, <30% LC and no lymphoid nodules. PR requires the following criteria for at least 2 months: >=50% decrease in LC, reduction in Ly (i.e., >=50% decrease in lymph node size or no increase or new lymph nodes), >=50% decrease in the size of liver and spleen and at least one of the following results: PL >100,000/µL or 50% improvement over Baseline(BL), Hb >11 g/dL or 50% improvement over BL, neutrophils>1500/μL. Nodular PR (nPR) indicates persistent nodules in the BM.
    End point type
    Secondary
    End point timeframe
    From the randomization date up to 60 months post the randomization date.
    End point values
    		 Any Ofatumumab Physician's Choice (PC) Ofatumumab Extended (OFA Ext) Ofatumumab Observation (OFA Observ.) OFA first Randomization Only (OFA FRO)
    Number of subjects analysed
    79
    43
    24
    13
    42
    Units: Participants
        CR|
    2
    2
    1
    1
    0
        PR|
    36
    12
    17
    7
    12
        nPR|
    1
    2
    0
    1
    0
        Stable Disease|
    34
    14
    6
    4
    24
        Progressive Disease|
    2
    10
    0
    0
    2
        Not Evaluable|
    0
    0
    0
    0
    0
        Missing|
    4
    3
    0
    0
    4
    Statistical analysis title
    		 ORR per Inv: Any OFA vs PC
    Comparison groups
    Physician's Choice (PC) v Any Ofatumumab
    Number of subjects included in analysis
    122
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4159 [1]
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.366
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.644
         upper limit
    		 2.899
    Notes
    [1] - Odds ratios and p-value are based on conditional logistic regression with interval and pooled stratum included in the Strata statement
    Statistical analysis title
    		 ORR per Inv: OFA Ext. vs OFA Observ.
    Comparison groups
    Ofatumumab Observation (OFA Observ.) v Ofatumumab Extended (OFA Ext)
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8866
    Method
    		 Regression, Logistic
    Parameter type
    		 Odds ratio (OR)
    Point estimate
    1.225
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.076
         upper limit
    		 19.862

    Secondary: Overall Survival

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    End point title
    		 Overall Survival
    End point description
    Overall survival (OS) is defined as the time from randomization to death due to any cause. Kaplan-Meier plots were used to estimate the reported median OS time.
    End point type
    Secondary
    End point timeframe
    From the randomization date up to 60 months post the randomization date.
    End point values
    		 Any Ofatumumab Physician's Choice (PC) Ofatumumab Extended (OFA Ext) Ofatumumab Observation (OFA Observ.) OFA first Randomization Only (OFA FRO)
    Number of subjects analysed
    79
    43
    24
    13
    42
    Units: Months
        median (confidence interval 95%)
    19.19 (12.19 to 29.11)
    14.52 (8.94 to 24.97)
    31.54 (19.19 to 51.25)
    45.50 (14.69 to 999)
    8.57 (4.93 to 16.76)
    Statistical analysis title
    		 OS: Any OFA vs PC
    Comparison groups
    Any Ofatumumab v Physician's Choice (PC)
    Number of subjects included in analysis
    122
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1732
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.48
         upper limit
    		 1.17
    Statistical analysis title
    		 O: OFA Ext. vs OFA Observ.
    Comparison groups
    Ofatumumab Extended (OFA Ext) v Ofatumumab Observation (OFA Observ.)
    Number of subjects included in analysis
    37
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.8128
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    1.11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.46
         upper limit
    		 2.68

    Secondary: Time to progression as assessed by IRC

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    End point title
    		 Time to progression as assessed by IRC [2]
    End point description
    Time to progression is defined as the time from the date of randomization to disease progression (PD). PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlarged lymph nodes (>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia. Participants who were alive and had not progressed at the time of analysis or if a progression event occurred after extensive lost-to-follow-up time were censored at the date of the last visit with adequate assessment.
    End point type
    Secondary
    End point timeframe
    From the randomization date up to 60 months post the randomization date.
    Notes
    [2] - 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: No statistical analysis was done for this endpoint.
    End point values
    		 Physician's Choice (PC) Any Ofatumumab (OFA) Ofatumumab Extended (OFA Ext) Ofatumumab Observation (OFA Observ.)
    Number of subjects analysed
    43
    56
    19
    11
    Units: Months
        median (confidence interval 95%)
    5.32 (2.14 to 8.08)
    6.31 (4.83 to 7.33)
    10.05 (7.23 to 13.80)
    7.16 (5.36 to 9.49)
    No statistical analyses for this end point

    Secondary: Time to next anti-cancer therapy by Investigator

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    End point title
    		 Time to next anti-cancer therapy by Investigator [3]
    End point description
    Time to next therapy is defined as the time from randomization until the start of the next line of treatment.
    End point type
    Secondary
    End point timeframe
    From the randomization date up to 60 months post the randomization date.
    Notes
    [3] - 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: No statistical analysis was done for this endpoint.
    End point values
    		 Physician's Choice (PC) Any Ofatumumab (OFA) Ofatumumab Extended (OFA Ext) Ofatumumab Observation (OFA Observ.)
    Number of subjects analysed
    43
    44
    12
    12
    Units: Months
        median (confidence interval 95%)
    6.54 (2.66 to 8.08)
    11.50 (8.51 to 13.80)
    15.47 (11.86 to 99.99)
    9.00 (8.08 to 14.16)
    No statistical analyses for this end point

    Secondary: Time to response as assessed by the IRC

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    End point title
    		 Time to response as assessed by the IRC [4]
    End point description
    Time to response is defined as the time from randomization to the first response (Complete Remission[CR], Complete Remission with incomplete bone marrow recovery[CRi], partial response[PR], or nodular PR[nPR]). CR(all the criteria at least 2 months after last treatment): no lymphadenopathy(Ly) > 1.5 cm/ hepatomegaly/ splenomegaly/ constitutional symptoms; neutrophils >1500 per microliter(µL), platelets(PL) >100,000/µL, hemoglobin(Hb) >11 grams/deciliter(g/dL), lymphocytes(LC) <4000/µL, bone marrow(BM) sample must be normocellular for age, <30% LC, no lymphoid nodule. CRi: CR criteria, persistent anemia/thrombocytopenia/neutropenia unrelated to CLL but related to drug toxicity. PR: >=50% decrease in LC, Ly, size of liver and spleen and at least one of the following results: PL >100,000/µL or 50% improvement over Baseline(BL), Hb >11 g/dL or 50% improvement over BL. nPR: persistent nodules BM. Participants with unknown or missing responses were considered as non-responders.
    End point type
    Secondary
    End point timeframe
    From the randomization date up to 60 months post the randomization date.
    Notes
    [4] - 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: No statistical analysis was done for this endpoint.
    End point values
    		 Physician's Choice (PC) Any Ofatumumab (OFA) Ofatumumab Extended (OFA Ext) Ofatumumab Observation (OFA Observ.)
    Number of subjects analysed
    7
    30
    18
    8
    Units: Months
        median (confidence interval 95%)
    2.56 (0.76 to 3.48)
    1.17 (1.02 to 1.91)
    1.86 (1.05 to 1.94)
    1.15 (0.92 to 1.94)
    No statistical analyses for this end point

    Secondary: Duration of response as assessed by the IRC

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    End point title
    		 Duration of response as assessed by the IRC [5]
    End point description
    DOR is defined as the time from the initial response (CR, CRi, nPR, or PR) to the first documented sign of PD or death due to any cause. PD requires at least one of the following: lymphadenopathy, appearance of any new lesion such as enlarged lymph nodes (>1.5 cm) spleen or liver or other infiltrates or an increase by 50% or more in the greatest diameter of any previous site; an increase by 50% or more in the previously noted enlargement of the liver or spleen, an increase by 50% or more in the numbers of blood lymphocytes with at least 5000 lymphocytes per microliter, transformation to a more aggressive histology, or occurrence of cytopenia attributable to chronic lymphocytic leukaemia. Par. who were alive and had not progressed at the time of analysis or if a progression event occurred after extensive lost-to-follow-up time (>= 12 weeks) were censored at the date of the last visit with adequate assessment. Par. with unknown or missing responses were considered as non-responders.
    End point type
    Secondary
    End point timeframe
    From the randomization date up to 60 months post the randomization date.
    Notes
    [5] - 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: No statistical analysis was done for this endpoint.
    End point values
    		 Physician's Choice (PC) Any Ofatumumab (OFA)
    Number of subjects analysed
    5
    23
    Units: Months
        median (confidence interval 95%)
    6.95 (4.47 to 9.99)
    6.24 (5.32 to 12.22)
    No statistical analyses for this end point

    Secondary: Number of participants with any adverse event (AE), any serious adverse event (SAE), any fatal serious adverse event (FSAE), or deaths

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    End point title
    		 Number of participants with any adverse event (AE), any serious adverse event (SAE), any fatal serious adverse event (FSAE), or deaths [6]
    End point description
    An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability or incapacity, is a congenital anomaly or birth defect.
    End point type
    Secondary
    End point timeframe
    From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy
    Notes
    [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: No statistical analysis was done for this endpoint.
    End point values
    		 Physician's Choice (PC) Any Ofatumumab (OFA) OFA Salvage Ofatumumab Extended (OFA Ext) Ofatumumab Observation (OFA Observ.) OFA first Randomization Only (OFA FRO)
    Number of subjects analysed
    43
    78
    22
    24
    13
    41
    Units: Participants
        Any AE|
    37
    71
    20
    22
    10
    39
        Any SAE|
    23
    43
    10
    12
    5
    26
        Any FSAE|
    6
    14
    5
    2
    3
    9
        Deaths|
    0
    1
    0
    0
    0
    1
    No statistical analyses for this end point

    Secondary: Number of participants with any adverse event (AE) of special interest

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    End point title
    		 Number of participants with any adverse event (AE) of special interest [7]
    End point description
    AEs of special interest included cytopenias (neutropenia [decreased neutrophil count], anaemia [decreased hemoglobin], and thrombocytopenia [decreased platelet count]), autoimmune haematologic complications (autoimmune haemolytic anaemia and haemolytic anaemia), infusion reactions, infections, mucocutaneous reactions, Tumour Lysis Syndrome (TLS), cardiovascular events, and small bowel obstruction.
    End point type
    Secondary
    End point timeframe
    From the first dose of study medication to 60 days after the last dose of study medication and until follow-up for SAEs unless initiation of subsequent anti-CLL therapy
    Notes
    [7] - 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: No statistical analysis was done for this endpoint.
    End point values
    		 Physician's Choice (PC) Any Ofatumumab (OFA) Ofatumumab Extended (OFA Ext) Ofatumumab Observation (OFA Observ.)
    Number of subjects analysed
    43
    78
    24
    13
    Units: Participants
        Any AE of decreased neutrophil count|
    15
    23
    11
    2
        Any AE of decreased hemoglobin|
    9
    9
    3
    2
        Any AE of decreased platelet count|
    5
    10
    3
    1
        Any AE of autoimmune haemolytic anaemia|
    2
    0
    0
    0
        Any AE of haemolytic anaemia|
    0
    1
    1
    0
        Any infusion related AE|
    11
    33
    8
    4
        Any AE of Infection|
    24
    46
    16
    8
        Any AE of mucocutaneous reaction|
    4
    20
    6
    3
        Any AE of TLS|
    1
    1
    0
    0
        Any AE of cardiovascular events|
    3
    13
    6
    0
        Any AE of small bowel obstruction|
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Mean Immunoglobulin (Ig) antibodies IgA, IgG, and IgM over time

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    End point title
    		 Mean Immunoglobulin (Ig) antibodies IgA, IgG, and IgM over time
    End point description
    Immunoglobulins or antibodies are large proteins used by the immune system to identify and neutralize foreign particles such as bacteria and viruses. Their normal blood levels indicate proper immune status. Low levels indicate immuno-suppression. IgA, IgG, and IgM were measured in the blood samples of the participants. Immunoglobulin testing was performed at Screening (SCR), Cycle 3 Week 4 (C3W4), Cycle 7 Week 4 (C3W4) ,Cycle 9 Week 4 (C3W4), 6 Month Follow-up Visit (6M FU), 9 Month Follow-up (9M FU), 12 Month Follow-up (12M FU), 18 Month Follow-up (18M FU), 24 Month Follow-up (24M FU), 30 Month Follow-up (30M FU), 36 Month Follow-up (36M FU), 42 Month Follow-up (42M FU). A cycle is defined as the time between one round of treatment until the start of the next round.
    End point type
    Secondary
    End point timeframe
    Screening and every 3 months during treatment, every 6 months after last treatment until PD or until 42 Month Follow-up Visit
    End point values
    		 Any Ofatumumab Physician's Choice (PC) OFA Salvage Ofatumumab Extended (OFA Ext) Ofatumumab Observation (OFA Observ.) OFA first Randomization Only (OFA FRO)
    Number of subjects analysed
    79
    43
    22
    24
    13
    41
    Units: Gram per liter
    arithmetic mean (standard deviation)
        IgA, SCR, n= 78, 41, 24, 13, 41, 0|
    0.793 ( 0.6680 )
    0.685 ( 0.5518 )
    999 ( 999 )
    0.807 ( 0.7426 )
    1.095 ( 0.7535 )
    0.688 ( 0.5749 )
        IgG, SCR, n=78, 41, 24, 13, 41, 0|
    6.909 ( 4.6836 )
    8.615 ( 12.1625 )
    999 ( 999 )
    6.270 ( 3.8573 )
    8.128 ( 4.7569 )
    6.898 ( 5.1142 )
        IgM, SCR, n=77,41, 24, 13, 40, 0|
    0.800 ( 1.3154 )
    0.601 ( 0.7061 )
    999 ( 999 )
    0.800 ( 1.6649 )
    0.468 ( 0.3801 )
    0.907 ( 1.2822 )
        IgA, C3W4, n=61, 23, 24, 12, 25, 17|
    0.721 ( 0.6355 )
    0.675 ( 0.4819 )
    0.486 ( 0.3868 )
    0.808 ( 0.7931 )
    0.977 ( 0.6458 )
    0.214 ( 0.3621 )
        IgG, C3W4, n=61, 23, 24, 12, 25, 17|
    5.925 ( 3.5059 )
    5.481 ( 2.1226 )
    5.974 ( 2.7992 )
    5.949 ( 3.4089 )
    7.232 ( 4.0103 )
    5.276 ( 3.3056 )
        IgM, C3W4, n=61, 23, 24, 12, 25, 17|
    0.692 ( 1.3420 )
    0.485 ( 0.4929 )
    0.488 ( 0.4816 )
    0.882 ( 1.9833 )
    0.429 ( 0.3497 )
    0.636 ( 0.7764 )
        IgA, C7W4, n=38, 0, 24, 12, 2, 10|
    0.793 ( 0.6608 )
    999 ( 999 )
    0.537 ( 0.4356 )
    0.723 ( 0.6730 )
    0.945 ( 0.6724 )
    0.725 ( 0.6011 )
        IgG, C7W4, n=38,0, 24, 12, 2, 10|
    6.250 ( 3.5225 )
    999 ( 999 )
    5.135 ( 2.6309 )
    5.817 ( 3.4944 )
    7.254 ( 3.7588 )
    5.420 ( 2.2062 )
        IgM, C7W4, n=38, 0, 24, 12, 2, 10|
    0.762 ( 1.7523 )
    999 ( 999 )
    0.447 ( 0.4732 )
    0.844 ( 2.1136 )
    0.414 ( 0.3400 )
    1.865 ( 2.3547 )
        IgA, C9W4, n=29, 0, 21, 8, 0, 7|
    0.719 ( 0.6336 )
    999 ( 999 )
    0.567 ( 0.3968 )
    0.630 ( 0.6005 )
    0.952 ( 0.6997 )
    999 ( 999 )
        IgG, C9W4, n=29, 0, 21, 8, 0, 7|
    6.164 ( 3.5886 )
    999 ( 999 )
    5.709 ( 2.1629 )
    5.553 ( 3.0792 )
    7.768 ( 4.5126 )
    999 ( 999 )
        IgM, C9W4, n=29, 0, 21, 8, 0, 7|
    0.853 ( 2.3484 )
    999 ( 999 )
    0.484 ( 0.4493 )
    0.973 ( 2.7574 )
    0.536 ( 0.4209 )
    999 ( 999 )
        IgA, 6M FU, n=0, 1, 0, 0, 0|
    999 ( 999 )
    0.880 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        IgG, 6M FU, n=0, 1, 0, 0, 0, 0|
    999 ( 999 )
    8.670 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        IgM, 6M FU, n=0, 1, 0, 0, 0, 0|
    999 ( 999 )
    0.200 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        IgA, 9M FU, n=2, 5, 2, 0, 0, 0|
    0.890 ( 0.0849 )
    0.510 ( 0.4585 )
    999 ( 999 )
    0.890 ( 0.0849 )
    999 ( 999 )
    999 ( 999 )
        IgG, 9M FU, n=2, 5, 2, 0, 0, 0|
    7.695 ( 0.9263 )
    5.016 ( 2.4292 )
    999 ( 999 )
    7.695 ( 0.9263 )
    999 ( 999 )
    999 ( 999 )
        IgM, 9M FU, n=2, 5, 2, 0, 0, 0|
    0.375 ( 0.1061 )
    0.246 ( 0.0706 )
    999 ( 999 )
    0.375 ( 0.1061 )
    999 ( 999 )
    999 ( 999 )
        IgA, 12M FU, n=10, 3, 7, 3, 0, 2|
    0.721 ( 0.8339 )
    0.983 ( 0.6029 )
    0.300 ( 0.00 )
    0.826 ( 0.9960 )
    0.477 ( 0.1595 )
    999 ( 999 )
        IgG, 12M FU, n=10, 3, 7, 3, 0, 2|
    6.423 ( 3.5390 )
    7.497 ( 1.5550 )
    4.935 ( 0.8273 )
    7.621 ( 3.3834 )
    3.627 ( 2.2938 )
    999 ( 999 )
        IgM, 12M FU, n=10, 3, 7, 3, 0, 2|
    0.384 ( 0.3463 )
    0.487 ( 0.2743 )
    0.240 ( 0.0566 )
    0.3334 ( 0.2833 )
    0.500 ( 0.5197 )
    999 ( 999 )
        IgA, 18M FU, n=8, 2, 7, 1, 0, 2|
    0.520 ( 0.2803 )
    1.095 ( 0.2616 )
    0.300 ( 0.000 )
    0.500 ( 0.2965 )
    0.660 ( 999 )
    999 ( 999 )
        IgG, 18M FU, n=8, 2, 7, 1, 0, 2|
    4.513 ( 2.0789 )
    6.620 ( 2.3759 )
    4.265 ( 1.1384 )
    4.206 ( 2.0405 )
    6.660 ( 999 )
    999 ( 999 )
        IgM, 18M FU, n=8, 2, 7, 1, 0, 2|
    0.417 ( 3.3156 )
    0.640 ( 0.2687 )
    0.240 ( 0.566 )
    0.317 ( 0.1490 )
    1.120 ( 999 )
    999 ( 999 )
        IgA, 24M FU, n=5, 1, 4, 1, 0, 0|
    0.540 ( 0.2667 )
    1.540 ( 999 )
    999 ( 999 )
    0.480 ( 0.2662 )
    0.780 ( 999 )
    999 ( 999 )
        IgG, 24M FU, n=5, 1, 4, 1, 0, 0|
    5.634 ( 2.4734 )
    10.900 ( 999 )
    999 ( 999 )
    5.098 ( 2.4977 )
    7.780 ( 999 )
    999 ( 999 )
        IgM, 24M FU, n=5, 1, 4, 1, 0, 0|
    0.490 ( 0.6321 )
    1.710 ( 999 )
    999 ( 999 )
    0.333 ( 0.0971 )
    1.120 ( 999 )
    999 ( 999 )
        IgA, 30M FU, n=2, 1, 2, 0, 0, 0|
    0.505 ( 0.2900 )
    1.380 ( 999 )
    999 ( 999 )
    0.505 ( 0.2900 )
    0.505 ( 0.2900 )
    999 ( 999 )
        IgG, 30M FU, n=2,1, 2, 0, 0, 0|
    3.460 ( 1.8809 )
    11.100 ( 999 )
    999 ( 999 )
    3.460 ( 1.8809 )
    999 ( 999 )
    999 ( 999 )
        IgM, 30M FU, n=2, 1, 2, 0, 0, 0,|
    0.400 ( 0.1131 )
    0.770 ( 999 )
    999 ( 999 )
    0.400 ( 0.1131 )
    999 ( 999 )
    999 ( 999 )
        IgA, 36M FU, n=2, 1, 2, 0, 0, 0|
    0.550 ( 0.3111 )
    1.680 ( 999 )
    999 ( 999 )
    0.550 ( 0.3111 )
    999 ( 999 )
    999 ( 999 )
        IgG, 36M FU, n=2,1, 2, 0, 0, 0|
    4.320 ( 2.2486 )
    13.600 ( 999 )
    999 ( 999 )
    4.320 ( 2.2486 )
    999 ( 999 )
    999 ( 999 )
        IgM, 36M FU, n=2, 1, 2, 0, 0, 0,|
    1.175 ( 0.2899 )
    0.720 ( 999 )
    999 ( 999 )
    1.175 ( 0.2899 )
    999 ( 999 )
    999 ( 999 )
        IgA, 42M FU, n=2, 1, 2, 0, 0, 0|
    0.545 ( 0.2051 )
    1.410 ( 999 )
    999 ( 999 )
    0.545 ( 0.2051 )
    999 ( 999 )
    999 ( 999 )
        IgG, 42M FU, n=2,1, 2, 0, 0, 0|
    4.425 ( 3.5143 )
    11.500 ( 999 )
    999 ( 999 )
    4.425 ( 3.5143 )
    999 ( 999 )
    999 ( 999 )
        IgM, 42M FU, n=2, 1, 2, 0, 0, 0|
    2.155 ( 0.8697 )
    0.470 ( 999 )
    999 ( 999 )
    2.155 ( 0.8697 )
    999 ( 999 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Number of participants who were positive or negative for Human Anti-Human Antibodies (HAHA) post-OFA therapy

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    End point title
    		 Number of participants who were positive or negative for Human Anti-Human Antibodies (HAHA) post-OFA therapy
    End point description
    The presence of HAHA in human serum was determined using a validated electrochemiluminescent assay in a multi-tier assay format. All samples were first assessed in a screening (SCR) assay, and the potential positive (Pos) samples were further tested in the confirmation (CNF) assays. Confirmed positives were reported as HAHA positive and titer was determined for each positive sample. The drug tolerance of the HAHA assay is 200 microgram/milliliter (µg/mL); thus, samples that tested negative in the assay and had ofatumumab concentrations no more than 200 µg/mL were considered as conclusive negative (Neg) results.
    End point type
    Secondary
    End point timeframe
    From the randomization date up to 60 months post the randomization date.
    End point values
    		 Any Ofatumumab (OFA) OFA Salvage Ofatumumab Extended (OFA Ext) Ofatumumab Observation (OFA Observ.) OFA first Randomization Only (OFA FRO)
    Number of subjects analysed
    78 [8]
    22 [9]
    24
    13
    41 [10]
    Units: Participants
        CNF Pos|
    0
    0
    0
    0
    0
        Neg and no OFA concentration <200 ug/mL|
    12
    4
    1
    1
    10
        Neg and at least one OFA concentration <200 ug/mL|
    57
    15
    23
    12
    22
    Notes
    [8] - n = (69, 69, 69)
    [9] - n = (19, 19, 19)
    [10] - n = (32, 32, 32)
    No statistical analyses for this end point

    Secondary: Changes from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, Chronic Lymphocytic Leukaemia 16 item module (EORTC QLQ-CLL 16)

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    End point title
    		 Changes from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, Chronic Lymphocytic Leukaemia 16 item module (EORTC QLQ-CLL 16)
    End point description
    The EORTC QLQ-CLL16 is comprised of 16 questions that address 5 domains of health-related quality of life (HRQoL) important in CLL. There are 4 multi-item scales – fatigue (2 items), treatment side effects ([TSE], 4 items), disease symptoms (disease effects scale [DES], 4 items), and infection (4 items) – and single item scales (social activities [Social Problems (SP) Scale] and future health worries[Future Health (FH) Scale].). These are measured on a four point scale where 1 = not at all and 4 = very much. These scores are transformed to give a rating from 0 – 100, where 0 =no symptoms or problems and 100 = a severe symptoms or problems. EORTC QLQ-CLL16 was assessed at Screening; Week (W) 12 (W4 of Cycle[C] 3), W24 (W4C6), W36 (W4C9), W48 (W4C13); during Follow-up which was every month for Months (M) 1-6, every 8 weeks for M7-12 and every 3 months up to M60; and then at PD.
    End point type
    Secondary
    End point timeframe
    From the randomization date up to 60 months post the randomization date.
    End point values
    		 Any Ofatumumab Physician's Choice (PC) Ofatumumab Extended (OFA Ext) Ofatumumab Observation (OFA Observ.)
    Number of subjects analysed
    79
    43
    24
    13
    Units: unit on a scale
    arithmetic mean (standard deviation)
        DES, C3W4, n=59,21, 24,12|
    -10.3 ( 17.60 )
    -6.3 ( 16.22 )
    -9.7 ( 12.20 )
    -10.4 ( 17.09 )
        DES, C6W4, n=44,13, 24,11|
    -8.5 ( 15.82 )
    -6.4 ( 16.37 )
    -8.3 ( 14.95 )
    -9.8 ( 18.19 )
        DES, C9W4, n=28, 0, 20, 8|
    -11 ( 17.72 )
    999 ( 999 )
    -7.5 ( 17.91 )
    -19.8 ( 14.73 )
        DES, C12W4, n=15, 0, 15, 0|
    -3.3 ( 21.78 )
    999 ( 999 )
    -3.3 ( 21.78 )
    999 ( 999 )
        DES, 3MFU, n=0, 0, 0, 0|
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        DES, 5MFU, n=0, 1, 0, 0|
    999 ( 999 )
    0 ( 999 )
    999 ( 999 )
    999 ( 999 )
        DES, 6MFU, n=0, 1, 0, 0|
    999 ( 999 )
    0 ( 999 )
    999 ( 999 )
    999 ( 999 )
        DES, 7MFU, n=0, 8, 0, 0|
    999 ( 999 )
    -14.6 ( 16.52 )
    999 ( 999 )
    999 ( 999 )
        DES, 9MFU, n=2, 6, 2, 0|
    0 ( 23.57 )
    -9.7 ( 9.74 )
    0 ( 23.57 )
    999 ( 999 )
        DES, 11MFU, n=1, 5, 1, 0|
    -25 ( 999 )
    -6.7 ( 18.07 )
    -2.5 ( 999 )
    999 ( 999 )
        DES, 12MFU, n=10, 3, 8, 2|
    -10.8 ( 14.19 )
    -2.8 ( 20.97 )
    -10.4 ( 14.6 )
    -12.5 ( 17.68 )
        DES, 15MFU, n=7, 3, 7, 0|
    -4.8 ( 13.49 )
    -5.6 ( 17.35 )
    -4.8 ( 13.49 )
    999 ( 999 )
        DES, 18MFU, n=5, 2, 5, 0|
    -3.3 ( 13.94 )
    -20.8 ( 17.68 )
    -3.3 ( 13.94 )
    999 ( 999 )
        DES, 21MFU, n=3, 2, 3, 0|
    5.6 ( 20.97 )
    -12.5 ( 5.89 )
    5.6 ( 20.97 )
    999 ( 999 )
        DES, 24MFU, n=2, 1, 2, 0|
    4.2 ( 5.89 )
    0 ( 999 )
    4.2 ( 5.89 )
    999 ( 999 )
        DES, 27MFU, n=1, 0, 1, 0|
    0 ( 999 )
    999 ( 999 )
    0 ( 999 )
    999 ( 999 )
        DES, 30MFU, n=1, 0, 1, 0|
    0 ( 999 )
    999 ( 999 )
    0 ( 999 )
    999 ( 999 )
        Fatigue Scale, C3W4, n=59, 21, 24, 12|
    -4 ( 24.04 )
    2.4 ( 21.91 )
    -2.1 ( 19.23 )
    -12.5 ( 24.75 )
        Fatigue Scale, C6W4, n=44, 13, 24, 11|
    -5.7 ( 19.99 )
    12.8 ( 29.78 )
    -0.7 ( 16.65 )
    -13.6 ( 19.46 )
        Fatigue Scale, C9W4, n=28, 0, 20, 8|
    -4.2 ( 25.1 )
    999 ( 999 )
    0 ( 24.78 )
    -14.6 ( 24.3 )
        Fatigue Scale, C12W4, n=15, 0, 15, 0|
    7.8 ( 33.85 )
    999 ( 999 )
    7.8 ( 33.85 )
    999 ( 999 )
        Fatigue Scale, 3MFU, n=0, 0, 0, 0|
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Fatigue Scale, 5MFU, n=0, 1, 0, 0|
    999 ( 999 )
    16.7 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Fatigue Scale, 6MFU, n=0, 1, 0, 0|
    999 ( 999 )
    16.7 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Fatigue Scale, 7MFU, n=0, 8, 0, 0|
    999 ( 999 )
    -14.6 ( 18.77 )
    999 ( 999 )
    999 ( 999 )
        Fatigue Scale, 9MFU, n=2, 6, 2, 0|
    41.7 ( 82.5 )
    -8.3 ( 22.97 )
    41.7 ( 82.5 )
    999 ( 999 )
        Fatigue Scale, 11MFU, n=1, 5, 1, 0|
    16.7 ( 999 )
    -6.7 ( 19 )
    -16.7 ( 999 )
    999 ( 999 )
        Fatigue Scale,12MFU, n=10, 3, 8, 2|
    5 ( 20.86 )
    -22.2 ( 9.62 )
    6.3 ( 21.71 )
    0 ( 23.57 )
        Fatigue Scale, 15MFU, n=7, 3, 7, 0|
    2.4 ( 22.42 )
    0 ( 16.67 )
    2.4 ( 22.42 )
    999 ( 999 )
        Fatigue Scale, 18MFU, n=5, 2, 5, 0|
    3.3 ( 21.73 )
    0 ( 0 )
    3.3 ( 21.73 )
    999 ( 999 )
        Fatigue Scale, 21MFU, n=3, 2, 3, 0|
    16.7 ( 28.87 )
    0 ( 23.57 )
    16.7 ( 28.87 )
    999 ( 999 )
        Fatigue Scale, 24MFU, n=2, 1, 2, 0|
    41.7 ( 58.93 )
    16.7 ( 999 )
    41.7 ( 58.93 )
    999 ( 999 )
        Fatigue Scale, 27MFU, n=1, 0, 1, 0|
    0 ( 999 )
    999 ( 999 )
    0 ( 999 )
    999 ( 999 )
        Fatigue Scale, 30MFU, n=1, 0, 1, 0|
    0 ( 999 )
    999 ( 999 )
    0 ( 999 )
    999 ( 999 )
        Future Health Scale, C3W4, n=58, 21,24, 11|
    -6.9 ( 27.04 )
    -7.9 ( 31.46 )
    -4.2 ( 22.66 )
    -6.1 ( 29.13 )
        Future Health Scale, C6W4, n=44, 13, 24, 11|
    -12.9 ( 29.83 )
    -5.1 ( 18.49 )
    -11.1 ( 25.38 )
    -24.2 ( 39.7 )
        Future Health Scale, C9W4, n=28, 0, 20, 8|
    -14.3 ( 27.86 )
    999 ( 999 )
    -11.7 ( 27.09 )
    -20.8 ( 30.54 )
        Future Health Scale, C12W4, n=15, 0, 15, 0|
    -4.4 ( 39.57 )
    999 ( 999 )
    -4.4 ( 39.57 )
    999 ( 999 )
        Future Health Scale, 3MFU, n=0, 0, 0, 0|
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Future Health Scale, 5MFU, n=0, 1, 0, 0|
    999 ( 999 )
    0 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Future Health Scale, 6MFU, n=0, 1, 0, 0|
    999 ( 999 )
    33.3 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Future Health Scale, 7MFU, n=0, 8, 0, 0|
    999 ( 999 )
    -12.5 ( 24.8 )
    999 ( 999 )
    999 ( 999 )
        Future Health Scale, 9MFU, n=2, 6, 2, 0|
    0 ( 47.14 )
    -22.2 ( 40.37 )
    0 ( 47.14 )
    999 ( 999 )
        Future Health Scale, 11MFU, n=1, 5, 1, 0|
    0 ( 999 )
    -13.3 ( 18.26 )
    0 ( 999 )
    999 ( 999 )
        Future Health Scale, 12MFU, n=10, 3, 8, 2|
    -10 ( 31.62 )
    -11.1 ( 19.25 )
    -4.2 ( 33.03 )
    -33.3 ( 0 )
        Future Health Scale, 15MFU, n=7, 3, 7, 0|
    19 ( 17.82 )
    -11.1 ( 19.25 )
    19 ( 17.82 )
    999 ( 999 )
        Future Health Scale, 18MFU, n=5, 2, 5, 0,|
    20 ( 18.26 )
    -16.7 ( 23.57 )
    20 ( 18.26 )
    999 ( 999 )
        Future Health Scale, 21MFU, n=3, 2, 3, 0|
    22.2 ( 19.25 )
    -16.7 ( 23.57 )
    22.2 ( 19.25 )
    999 ( 999 )
        Future Health Scale, 24MFU, n=2, 1, 2, 0|
    0 ( 999 )
    0 ( 999 )
    33.3 ( 47.14 )
    999 ( 999 )
        Future Health Scale, 27MFU, n=1, 0, 1, 0|
    0 ( 999 )
    999 ( 999 )
    0 ( 999 )
    999 ( 999 )
        Future Health Scale, 30MFU, n=1, 0, 1, 0|
    0 ( 999 )
    999 ( 999 )
    0 ( 999 )
    999 ( 999 )
        Infection Scale, C3W4, n=59, 21, 24, 12|
    2.1 ( 23.6 )
    3.2 ( 19.63 )
    -1 ( 20.01 )
    -5.6 ( 12.48 )
        Infection Scale, C6W4, n=44, 13, 24, 11|
    -3.7 ( 22.66 )
    12.2 ( 25.6 )
    -5.6 ( 19.91 )
    -6.8 ( 19.3 )
        Infection Scale,C9W4, n=28, 0, 20, 8|
    -7.4 ( 18.61 )
    999 ( 999 )
    -7.5 ( 16.86 )
    -7.3 ( 23.75 )
        Infection Scale, C12W4, n=15, 0, 15, 0|
    -11.7 ( 14.02 )
    999 ( 999 )
    -11.7 ( 14.02 )
    999 ( 999 )
        Infection Scale, 3MFU, n=0, 0, 0, 0|
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Infection Scale, 5MFU, n=0, 1, 0, 0|
    999 ( 999 )
    0 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Infection Scale, 6MFU, n=0, 1, 0, 0|
    999 ( 999 )
    8.3 ( 999 )
    999 ( 999 )
    999 ( 999 )
        Infection Scale, 7MFU, n=0, 8, 0, 0|
    999 ( 999 )
    -9.4 ( 12.15 )
    999 ( 999 )
    999 ( 999 )
        Infection Scale, 9MFU, n=2, 6, 2, 0|
    16.7 ( 23.57 )
    0 ( 13.94 )
    16.7 ( 23.57 )
    999 ( 999 )
        Infection Scale, 11MFU, n=1, 5, 1, 0|
    0 ( 999 )
    -6.7 ( 12.36 )
    0 ( 999 )
    999 ( 999 )
        Infection Scale, 12MFU, n=10, 3, 8, 2|
    -7.5 ( 20.58 )
    2.8 ( 12.73 )
    -6.2 ( 20.29 )
    -12.5 ( 29.46 )
        Infection Scale, 15MFU, n=7, 3, 7, 0|
    -2.4 ( 17.82 )
    -2.8 ( 20.97 )
    -2.4 ( 17.82 )
    999 ( 999 )
        Infection Scale, 18MFU, n=5, 2, 5, 0|
    5 ( 12.64 )
    -8.3 ( 11.79 )
    5 ( 12.64 )
    999 ( 999 )
        Infection Scale, 21MFU, n=3, 2, 3, 0|
    2.8 ( 12.73 )
    8.3 ( 0 )
    2.8 ( 12.73 )
    999 ( 999 )
        Infection Scale, 24MFU, n=2, 1, 2, 0|
    0 ( 0 )
    8.3 ( 999 )
    0 ( 0 )
    999 ( 999 )
        Infection Scale, 27MFU, n=1, 0, 1, 0|
    0 ( 999 )
    999 ( 999 )
    0 ( 999 )
    999 ( 999 )
        Infection Scale, 30MFU, n=1, 0, 1, 0|
    0 ( 999 )
    999 ( 999 )
    0 ( 999 )
    999 ( 999 )
        SP Scale, C3W4, n=59, 21, 24, 12|
    -9 ( 27.56 )
    3.2 ( 36.37 )
    -11.1 ( 23.4 )
    -13.9 ( 30.01 )
        SP Scale, C6W4, n=44, 13, 24, 11|
    -10.6 ( 27.63 )
    10.3 ( 31.58 )
    -9.7 ( 25.02 )
    -15.2 ( 31.14 )
        SP Scale, C9W4, n=28, 0, 20, 8|
    -13.1 ( 27.72 )
    999 ( 999 )
    -11.7 ( 29.17 )
    -16.7 ( 25.2 )
        SP Scale, C12W4, n=15, 0, 15, 0|
    -11.1 ( 37.09 )
    999 ( 999 )
    -11.1 ( 37.09 )
    999 ( 999 )
        SP Scale, 3MFU, n=0, 0, 0, 0|
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        SP Scale, 5MFU, n=0, 1, 0, 0|
    999 ( 999 )
    -33.3 ( 999 )
    999 ( 999 )
    999 ( 999 )
        SP Scale, 6MFU, n=0, 1, 0, 0|
    999 ( 999 )
    -66.7 ( 999 )
    999 ( 999 )
    999 ( 999 )
        SP Scale, 7MFU, n=0, 8, 0, 0|
    999 ( 999 )
    -16.7 ( 25.2 )
    999 ( 999 )
    999 ( 999 )
        SP Scale, 9MFU, n=2, 6, 2, 0|
    16.7 ( 70.71 )
    -5.6 ( 32.77 )
    16.7 ( 70.71 )
    999 ( 999 )
        SP Scale, 11MFU, n=1, 5, 1, 0|
    -33.3 ( 999 )
    -6.7 ( 36.51 )
    -33.3 ( 999 )
    999 ( 999 )
        SP Scale, 12MFU, n=10, 3, 8, 2|
    -16.7 ( 23.57 )
    -22.2 ( 19.25 )
    -16.7 ( 25.2 )
    -16.7 ( 23.57 )
        SP Scale, 15MFU, n=7, 3, 7, 0|
    -9.5 ( 37.09 )
    -11.1 ( 19.25 )
    -9.5 ( 37.09 )
    999 ( 999 )
        SP Scale, 18MFU, n=5, 2, 5, 0|
    0 ( 23.57 )
    -16.7 ( 23.57 )
    0 ( 23.57 )
    999 ( 999 )
        SP Scale, 21MFU, n=3, 2, 3, 0|
    -22.2 ( 38.49 )
    -16.7 ( 23.57 )
    -22.2 ( 38.49 )
    999 ( 999 )
        SP Scale, 24MFU, n=2, 1, 2, 0|
    33.3 ( 47.14 )
    0 ( 999 )
    33.3 ( 47.14 )
    999 ( 999 )
        SP Scale, 27MFU, n=1, 0, 1, 0|
    0 ( 999 )
    999 ( 999 )
    0 ( 999 )
    999 ( 999 )
        SP Scale, 30MFU, n=1, 0, 1, 0|
    0 ( 999 )
    999 ( 999 )
    0 ( 999 )
    999 ( 999 )
        TSE Scale, C3W4, n=59, 21, 24, 12|
    -4.8 ( 15.33 )
    -1.5 ( 16.82 )
    -2.4 ( 10.85 )
    -8.3 ( 13.76 )
        TSE Scale, C6W4, n=44, 13, 24, 11|
    -4.2 ( 14.33 )
    3.2 ( 12.52 )
    -0.2 ( 11.32 )
    -9.1 ( 16.44 )
        TSE Scale, C9W4, n=28, 0, 20, 8|
    -5.4 ( 15.75 )
    999 ( 999 )
    -3.7 ( 13.91 )
    -9.4 ( 20.14 )
        TSE Scale, C12W4, n=15, 0, 15, 0|
    -2.8 ( 14.66 )
    999 ( 999 )
    -2.8 ( 14.66 )
    999 ( 999 )
        TSE Scale, 3MFU, n=0, 0, 0, 0|
    0 ( 0 )
    0 ( 0 )
    999 ( 999 )
    999 ( 999 )
        TSE Scale, 5MFU, n=0, 1, 0, 0|
    999 ( 999 )
    16.7 ( 999 )
    999 ( 999 )
    999 ( 999 )
        TSE Scale, 6MFU, n=0, 1, 0, 0|
    999 ( 999 )
    16.7 ( 999 )
    999 ( 999 )
    999 ( 999 )
        TSE Scale, 7MFU, n=0, 8, 0, 0|
    999 ( 999 )
    -8.3 ( 17.82 )
    999 ( 999 )
    999 ( 999 )
        TSE Scale, 9MFU, n=2, 6, 2, 0|
    8.3 ( 11.79 )
    -1.4 ( 9.74 )
    8.3 ( 11.79 )
    999 ( 999 )
        TSE Scale, 11MFU, n=1, 5, 1, 0|
    0 ( 999 )
    -1.7 ( 14.91 )
    0 ( 999 )
    999 ( 999 )
        TSE Scale, 12MFU, n=10, 3, 8, 2|
    -4.2 ( 19.74 )
    2.8 ( 12.73 )
    0 ( 12.6 )
    -20.8 ( 41.25 )
        TSE Scale, 15MFU, n=7, 3, 7, 0|
    -8.3 ( 12.73 )
    2.8 ( 9.62 )
    -8.3 ( 12.73 )
    999 ( 999 )
        TSE Scale, 18MFU, n=5, 2, 5, 0|
    6.7 ( 16.03 )
    0 ( 11.79 )
    6.7 ( 16.03 )
    999 ( 999 )
        TSE Scale, 21MFU, n=3, 2, 3, 0|
    8.3 ( 22.05 )
    0 ( 0 )
    8.3 ( 22.05 )
    999 ( 999 )
        TSE Scale, 24MFU, n=2, 1, 2, 0|
    4.2 ( 5.89 )
    0 ( 999 )
    4.2 ( 5.89 )
    999 ( 999 )
        TSE Scale, 27MFU, n=1, 0, 1, 0|
    8.3 ( 999 )
    999 ( 999 )
    8.3 ( 999 )
    999 ( 999 )
        TSE Scale, 30MFU, n=1, 0, 1, 0|
    0 ( 999 )
    999 ( 999 )
    0 ( 999 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Mean Health Change Questionnaire (HCQ) score

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    End point title
    		 Mean Health Change Questionnaire (HCQ) score
    End point description
    The HCQ consists of a single question in which the participant is asked if he/she has experienced any change in his/her health overall since beginning the study. For HCQ, values from 1 to 9 were assigned to the 9 responses in the HCQ questionnaire, ranging from 1 for ‘my health is a great deal better’ to 9 for ‘my health is a great deal worse’ since the beginning of the study. A score of 3 or less indicates improvement from Baseline. HCQ was assessed at Screening; Week (W) 12 (W4 of Cycle[C] 3), W24 (W4C6), W36 (W4C9), W48 (W4C13); during follow-up which was every month for Months 1-6, every 8 weeks for M7-12 and every 3 months up to M60; and then at PD..
    End point type
    Secondary
    End point timeframe
    From the randomization date up to 60 months post the randomization date.
    End point values
    		 Any Ofatumumab Physician's Choice (PC) OFA Salvage Ofatumumab Extended (OFA Ext) Ofatumumab Observation (OFA Observ.) OFA first Randomization Only (OFA FRO)
    Number of subjects analysed
    79
    43
    22
    24
    13
    41
    Units: Unit on a scale
    arithmetic mean (standard deviation)
        C3W4, n=60, 21, 24, 12, 24, 17|
    2.8 ( 1.57 )
    3.9 ( 2.01 )
    3.1 ( 1.92 )
    2.5 ( 1.44 )
    2.8 ( 0.97 )
    3.2 ( 1.90 )
        C6W4, n=44, 13, 24, 11, 9, 12|
    3.2 ( 2.04 )
    3.5 ( 2.37 )
    3.0 ( 2.00 )
    2.7 ( 1.66 )
    2.9 ( 1.76 )
    5.1 ( 2.37 )
        C9W4, n=28, 0, 20, 8, 0, 7|
    2.08 ( 1.60 )
    999 ( 999 )
    3.1 ( 2.48 )
    2.5 ( 1.36 )
    3.5 ( 2.00 )
    999 ( 999 )
        C12W4, n=14, 0, 14, 0, 0, 4|
    2.6 ( 1.99 )
    999 ( 999 )
    3.0 ( 1.83 )
    2.6 ( 1.99 )
    999 ( 999 )
    999 ( 999 )
        3MFU, n=0, 0, 0, 0, 0, 1|
    999 ( 999 )
    999 ( 999 )
    3.0 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        5MFU, n=0, 1, 0, 0, 0, 0|
    999 ( 999 )
    5.0 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        6MFU, n=0, 1, 0, 0, 0, 0|
    999 ( 999 )
    3.0 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 9999 )
    999 ( 999 )
        7MFU, n=0, 8, 0, 0, 0, 0|
    999 ( 999 )
    2.4 ( 1.30 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
    999 ( 999 )
        9MFU, n=2, 6, 2, 0, 0, 0|
    6.5 ( 2.12 )
    3.5 ( 2.07 )
    999 ( 999 )
    6.5 ( 2.12 )
    999 ( 999 )
    999 ( 999 )
        11MFU, n=1, 5, 1, 0, 0, 0|
    5.0 ( 999 )
    3.0 ( 2.35 )
    999 ( 999 )
    5.0 ( 999 )
    999 ( 999 )
    999 ( 999 )
        12MFU, n=10, 3, 8, 2, 0, 2|
    3.4 ( 2.07 )
    2.3 ( 1.53 )
    2.0 ( 1.41 )
    3.5 ( 2.27 )
    3.0 ( 1.41 )
    999 ( 999 )
        15MFU, n=10, 3, 9, 1, 0, 3|
    3.5 ( 2.27 )
    3.7 ( 1.53 )
    2.0 ( 1.00 )
    3.7 ( 2.35 )
    2.0 ( 999 )
    999 ( 999 )
        18MFU, n=7, 2, 6, 1, 0, 2|
    2.6 ( 2.15 )
    4.5 ( 0.71 )
    4.0 ( 4.24 )
    2.8 ( 2.23 )
    1.0 ( 999 )
    999 ( 999 )
        21MFU, n=5, 2, 4, 1, 0, 0|
    2.0 ( 1.22 )
    6.0 ( 1.41 )
    999 ( 999 )
    2.3 ( 1.26 )
    1.0 ( 999 )
    999 ( 999 )
        24MFU, n=4, 1, 3, 1, 0, 0|
    2.5 ( 3.00 )
    4.0 ( 999 )
    999 ( 999 )
    3.0 ( 3.46 )
    1.0 ( 999 )
    999 ( 999 )
        27MFU, n=3, 1, 2, 0, 0, 0|
    2.7 ( 2.89 )
    5.0 ( 999 )
    999 ( 999 )
    3.5 ( 3.54 )
    1.0 ( 999 )
    999 ( 999 )
        30MFU, n=1, 1, 1, 0, 0, 0|
    1.0 ( 999 )
    5.0 ( 999 )
    999 ( 999 )
    1.0 ( 999 )
    999 ( 999 )
    999 ( 999 )
        33MFU, n=2, 1, 2, 0, 0, 0|
    3.0 ( 2.83 )
    5.0 ( 999 )
    999 ( 999 )
    3.0 ( 2.83 )
    3.0 ( 2.83 )
    999 ( 999 )
        36MFU, n=2, 1, 2, 0, 0, 0|
    3.0 ( 2.83 )
    5.0 ( 999 )
    999 ( 999 )
    3.0 ( 2.83 )
    3.0 ( 2.83 )
    999 ( 999 )
        39MFU, n=2, 1, 2, 0, 0, 0|
    4.0 ( 4.24 )
    7.0 ( 999 )
    999 ( 999 )
    4.0 ( 4.24 )
    4.0 ( 4.24 )
    999 ( 999 )
        42MFU, n=2, 1, 2, 0, 0, 0|
    3.0 ( 2.83 )
    5.0 ( 999 )
    999 ( 999 )
    3.0 ( 2.83 )
    3.0 ( 3.83 )
    999 ( 999 )
        45MFU, n=1, 1, 1, 0, 0, 0|
    1.0 ( 999 )
    7.0 ( 999 )
    999 ( 999 )
    1.0 ( 999 )
    1.0 ( 999 )
    999 ( 999 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    SAEs & AEs were collected from 1st dose to 60 days after last dose of study medication & until end of FU period for SAEs unless initiation of subsequent anti-CLL therapy. AEs reported in this record - from date of FP First Treatment until LPLV
    Adverse event reporting additional description
    Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.0
    Reporting groups
    Reporting group title
    Any Ofatumumab
    Reporting group description
    		 Any Ofatumumab

    Reporting group title
    Ofatumumab extended
    Reporting group description
    		 Ofatumumab extended

    Reporting group title
    Ofatumumab observation
    Reporting group description
    		 Ofatumumab observation

    Reporting group title
    Ofatumumab
    Reporting group description
    		 Ofatumumab

    Reporting group title
    Physicians choice
    Reporting group description
    		 Physicians choice

    Reporting group title
    Ofatumumab salvage
    Reporting group description
    		 Ofatumumab salvage

    Serious adverse events
    		 Any Ofatumumab Ofatumumab extended Ofatumumab observation Ofatumumab Physicians choice Ofatumumab salvage
    Total subjects affected by serious adverse events
         subjects affected / exposed
    43 / 78 (55.13%)
    12 / 24 (50.00%)
    5 / 13 (38.46%)
    26 / 41 (63.41%)
    23 / 43 (53.49%)
    10 / 22 (45.45%)
         number of deaths (all causes)
    13
    1
    1
    11
    8
    3
         number of deaths resulting from adverse events
    5
    1
    1
    3
    5
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Large cell lung cancer
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Vascular disorders
    Hypotension
         subjects affected / exposed
    2 / 78 (2.56%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    2 / 41 (4.88%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombophlebitis
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chills
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Death
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 78 (1.28%)
    1 / 24 (4.17%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    4 / 78 (5.13%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    4 / 41 (9.76%)
    3 / 43 (6.98%)
    2 / 22 (9.09%)
         occurrences causally related to treatment / all
    6 / 7
    0 / 0
    0 / 0
    6 / 7
    2 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Bronchitis chronic
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 78 (1.28%)
    1 / 24 (4.17%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydrothorax
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung disorder
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infiltration
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Obstructive airways disorder
         subjects affected / exposed
    1 / 78 (1.28%)
    1 / 24 (4.17%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    2 / 78 (2.56%)
    1 / 24 (4.17%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary oedema
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Blood pressure decreased
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    C-reactive protein increased
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Overdose
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Atrial fibrillation
         subjects affected / exposed
    2 / 78 (2.56%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    2 / 41 (4.88%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 3
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac arrest
         subjects affected / exposed
    2 / 78 (2.56%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    2 / 41 (4.88%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    Cardiac failure
         subjects affected / exposed
    2 / 78 (2.56%)
    1 / 24 (4.17%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
    0 / 0
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 1
    0 / 0
    Cardiac failure acute
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    2 / 22 (9.09%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    Cardiovascular insufficiency
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Supraventricular tachycardia
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular tachycardia
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Chorea
         subjects affected / exposed
    1 / 78 (1.28%)
    1 / 24 (4.17%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 78 (2.56%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    1 / 41 (2.44%)
    4 / 43 (9.30%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
    1 / 1
    1 / 1
    2 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Autoimmune haemolytic anaemia
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    2 / 43 (4.65%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    7 / 78 (8.97%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    6 / 41 (14.63%)
    4 / 43 (9.30%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    5 / 8
    0 / 0
    1 / 1
    4 / 7
    6 / 6
    0 / 1
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Leukopenia
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Chorioretinal atrophy
         subjects affected / exposed
    1 / 78 (1.28%)
    1 / 24 (4.17%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 78 (1.28%)
    1 / 24 (4.17%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug-induced liver injury
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis toxic
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    Hepatotoxicity
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hydronephrosis
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal failure
         subjects affected / exposed
    2 / 78 (2.56%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    2 / 41 (4.88%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
    0 / 0
    1 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Hypercalcaemia of malignancy
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abscess neck
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Acute sinusitis
         subjects affected / exposed
    1 / 78 (1.28%)
    1 / 24 (4.17%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 78 (1.28%)
    1 / 24 (4.17%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Empyema
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterocolitis infectious
         subjects affected / exposed
    1 / 78 (1.28%)
    1 / 24 (4.17%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal fungal infection
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis B
         subjects affected / exposed
    1 / 78 (1.28%)
    1 / 24 (4.17%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis E
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infection
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningitis
         subjects affected / exposed
    2 / 78 (2.56%)
    1 / 24 (4.17%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meningitis aseptic
         subjects affected / exposed
    1 / 78 (1.28%)
    1 / 24 (4.17%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    2 / 43 (4.65%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 2
    0 / 0
    Otosalpingitis
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    9 / 78 (11.54%)
    3 / 24 (12.50%)
    0 / 13 (0.00%)
    6 / 41 (14.63%)
    7 / 43 (16.28%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    3 / 10
    0 / 4
    0 / 0
    3 / 6
    2 / 8
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 2
    1 / 1
    0 / 0
    Progressive multifocal leukoencephalopathy
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    Pseudomembranous colitis
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    4 / 43 (9.30%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    2 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin infection
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 78 (2.56%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    1 / 22 (4.55%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral tonsillitis
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyperglycaemia
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoalbuminaemia
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Malnutrition
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tumour lysis syndrome
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Any Ofatumumab Ofatumumab extended Ofatumumab observation Ofatumumab Physicians choice Ofatumumab salvage
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    62 / 78 (79.49%)
    20 / 24 (83.33%)
    9 / 13 (69.23%)
    33 / 41 (80.49%)
    28 / 43 (65.12%)
    13 / 22 (59.09%)
    Vascular disorders
    Flushing
         subjects affected / exposed
    3 / 78 (3.85%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    2 / 41 (4.88%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    6
    0
    1
    5
    0
    0
    Hypertension
         subjects affected / exposed
    5 / 78 (6.41%)
    2 / 24 (8.33%)
    0 / 13 (0.00%)
    3 / 41 (7.32%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    5
    2
    0
    3
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    3 / 78 (3.85%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    3 / 41 (7.32%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    3
    0
    0
    3
    0
    0
    Chills
         subjects affected / exposed
    9 / 78 (11.54%)
    1 / 24 (4.17%)
    2 / 13 (15.38%)
    6 / 41 (14.63%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences all number
    18
    1
    3
    14
    1
    0
    Fatigue
         subjects affected / exposed
    3 / 78 (3.85%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    2 / 41 (4.88%)
    4 / 43 (9.30%)
    0 / 22 (0.00%)
         occurrences all number
    3
    0
    1
    2
    4
    0
    Oedema peripheral
         subjects affected / exposed
    2 / 78 (2.56%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    1 / 41 (2.44%)
    3 / 43 (6.98%)
    0 / 22 (0.00%)
         occurrences all number
    2
    0
    1
    1
    3
    0
    Peripheral swelling
         subjects affected / exposed
    4 / 78 (5.13%)
    1 / 24 (4.17%)
    0 / 13 (0.00%)
    3 / 41 (7.32%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences all number
    4
    1
    0
    3
    1
    0
    Pyrexia
         subjects affected / exposed
    8 / 78 (10.26%)
    2 / 24 (8.33%)
    1 / 13 (7.69%)
    5 / 41 (12.20%)
    3 / 43 (6.98%)
    1 / 22 (4.55%)
         occurrences all number
    14
    3
    2
    9
    3
    2
    Reproductive system and breast disorders
    Erectile dysfunction
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    11 / 78 (14.10%)
    3 / 24 (12.50%)
    2 / 13 (15.38%)
    6 / 41 (14.63%)
    1 / 43 (2.33%)
    2 / 22 (9.09%)
         occurrences all number
    14
    4
    2
    8
    1
    2
    Dyspnoea
         subjects affected / exposed
    3 / 78 (3.85%)
    1 / 24 (4.17%)
    1 / 13 (7.69%)
    1 / 41 (2.44%)
    2 / 43 (4.65%)
    1 / 22 (4.55%)
         occurrences all number
    3
    1
    1
    1
    2
    1
    Nasal obstruction
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Productive cough
         subjects affected / exposed
    4 / 78 (5.13%)
    0 / 24 (0.00%)
    2 / 13 (15.38%)
    2 / 41 (4.88%)
    0 / 43 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    4
    0
    2
    2
    0
    1
    Psychiatric disorders
    Depressed mood
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    4 / 78 (5.13%)
    1 / 24 (4.17%)
    1 / 13 (7.69%)
    2 / 41 (4.88%)
    1 / 43 (2.33%)
    1 / 22 (4.55%)
         occurrences all number
    6
    1
    3
    2
    1
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    3 / 78 (3.85%)
    1 / 24 (4.17%)
    1 / 13 (7.69%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    5
    1
    3
    1
    0
    1
    Blood bilirubin increased
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Haemoglobin decreased
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    1
    0
    Lymphocyte count decreased
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Neutrophil count decreased
         subjects affected / exposed
    2 / 78 (2.56%)
    1 / 24 (4.17%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences all number
    4
    3
    1
    0
    1
    0
    Weight decreased
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    1 / 43 (2.33%)
    2 / 22 (9.09%)
         occurrences all number
    1
    0
    0
    1
    1
    2
    Weight increased
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    1 / 22 (4.55%)
         occurrences all number
    1
    0
    1
    0
    1
    2
    Injury, poisoning and procedural complications
    Arthropod bite
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Contusion
         subjects affected / exposed
    3 / 78 (3.85%)
    2 / 24 (8.33%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    3
    2
    1
    0
    0
    0
    Cardiac disorders
    Cardiac failure
         subjects affected / exposed
    3 / 78 (3.85%)
    2 / 24 (8.33%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    3
    2
    0
    1
    0
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    2 / 22 (9.09%)
         occurrences all number
    1
    0
    0
    1
    0
    2
    Headache
         subjects affected / exposed
    3 / 78 (3.85%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    3 / 41 (7.32%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    3
    0
    0
    3
    0
    0
    Hypoaesthesia
         subjects affected / exposed
    2 / 78 (2.56%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    2
    0
    1
    1
    0
    0
    Muscle spasticity
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Paraesthesia
         subjects affected / exposed
    3 / 78 (3.85%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    2 / 41 (4.88%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    4
    0
    1
    3
    0
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    5 / 78 (6.41%)
    2 / 24 (8.33%)
    0 / 13 (0.00%)
    3 / 41 (7.32%)
    5 / 43 (11.63%)
    1 / 22 (4.55%)
         occurrences all number
    5
    2
    0
    3
    8
    4
    Leukopenia
         subjects affected / exposed
    2 / 78 (2.56%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    1 / 41 (2.44%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences all number
    3
    0
    1
    2
    2
    0
    Lymphocytosis
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Neutropenia
         subjects affected / exposed
    15 / 78 (19.23%)
    10 / 24 (41.67%)
    1 / 13 (7.69%)
    4 / 41 (9.76%)
    8 / 43 (18.60%)
    3 / 22 (13.64%)
         occurrences all number
    33
    24
    1
    8
    9
    6
    Thrombocytopenia
         subjects affected / exposed
    8 / 78 (10.26%)
    3 / 24 (12.50%)
    1 / 13 (7.69%)
    4 / 41 (9.76%)
    3 / 43 (6.98%)
    1 / 22 (4.55%)
         occurrences all number
    11
    6
    1
    4
    4
    1
    Ear and labyrinth disorders
    Ear congestion
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Hypoacusis
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Vertigo
         subjects affected / exposed
    2 / 78 (2.56%)
    1 / 24 (4.17%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    3
    2
    1
    0
    0
    0
    Eye disorders
    Visual impairment
         subjects affected / exposed
    2 / 78 (2.56%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    2
    0
    1
    1
    0
    0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    4 / 78 (5.13%)
    2 / 24 (8.33%)
    0 / 13 (0.00%)
    2 / 41 (4.88%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences all number
    4
    2
    0
    2
    1
    0
    Constipation
         subjects affected / exposed
    3 / 78 (3.85%)
    1 / 24 (4.17%)
    1 / 13 (7.69%)
    1 / 41 (2.44%)
    1 / 43 (2.33%)
    1 / 22 (4.55%)
         occurrences all number
    4
    1
    1
    2
    1
    1
    Diarrhoea
         subjects affected / exposed
    5 / 78 (6.41%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    5 / 41 (12.20%)
    4 / 43 (9.30%)
    2 / 22 (9.09%)
         occurrences all number
    9
    0
    0
    9
    4
    2
    Nausea
         subjects affected / exposed
    8 / 78 (10.26%)
    2 / 24 (8.33%)
    1 / 13 (7.69%)
    5 / 41 (12.20%)
    5 / 43 (11.63%)
    1 / 22 (4.55%)
         occurrences all number
    11
    3
    1
    7
    7
    2
    Vomiting
         subjects affected / exposed
    4 / 78 (5.13%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    4 / 41 (9.76%)
    3 / 43 (6.98%)
    0 / 22 (0.00%)
         occurrences all number
    4
    0
    0
    4
    3
    0
    Hepatobiliary disorders
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Skin and subcutaneous tissue disorders
    Dry skin
         subjects affected / exposed
    3 / 78 (3.85%)
    1 / 24 (4.17%)
    1 / 13 (7.69%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    4
    2
    1
    1
    0
    0
    Pruritus
         subjects affected / exposed
    5 / 78 (6.41%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    5 / 41 (12.20%)
    2 / 43 (4.65%)
    0 / 22 (0.00%)
         occurrences all number
    7
    0
    0
    7
    2
    0
    Rash
         subjects affected / exposed
    3 / 78 (3.85%)
    1 / 24 (4.17%)
    1 / 13 (7.69%)
    1 / 41 (2.44%)
    2 / 43 (4.65%)
    2 / 22 (9.09%)
         occurrences all number
    3
    1
    1
    1
    2
    2
    Skin lesion
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    1
    0
    Urticaria
         subjects affected / exposed
    3 / 78 (3.85%)
    2 / 24 (8.33%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences all number
    4
    3
    1
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    2 / 78 (2.56%)
    0 / 24 (0.00%)
    2 / 13 (15.38%)
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences all number
    2
    0
    2
    0
    1
    0
    Back pain
         subjects affected / exposed
    4 / 78 (5.13%)
    1 / 24 (4.17%)
    0 / 13 (0.00%)
    3 / 41 (7.32%)
    1 / 43 (2.33%)
    1 / 22 (4.55%)
         occurrences all number
    5
    1
    0
    4
    1
    1
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    6 / 78 (7.69%)
    4 / 24 (16.67%)
    0 / 13 (0.00%)
    2 / 41 (4.88%)
    3 / 43 (6.98%)
    1 / 22 (4.55%)
         occurrences all number
    7
    4
    0
    3
    4
    1
    Cytomegalovirus infection
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    4 / 43 (9.30%)
    0 / 22 (0.00%)
         occurrences all number
    0
    0
    0
    0
    4
    0
    Eye infection
         subjects affected / exposed
    2 / 78 (2.56%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    1 / 41 (2.44%)
    0 / 43 (0.00%)
    1 / 22 (4.55%)
         occurrences all number
    2
    0
    1
    1
    0
    1
    Fungal infection
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences all number
    2
    0
    2
    0
    1
    0
    Gastroenteritis
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    5 / 78 (6.41%)
    3 / 24 (12.50%)
    1 / 13 (7.69%)
    1 / 41 (2.44%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences all number
    6
    4
    1
    1
    1
    0
    Pneumonia
         subjects affected / exposed
    4 / 78 (5.13%)
    3 / 24 (12.50%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    1 / 43 (2.33%)
    0 / 22 (0.00%)
         occurrences all number
    4
    3
    0
    1
    1
    0
    Respiratory tract infection
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Sialoadenitis
         subjects affected / exposed
    1 / 78 (1.28%)
    0 / 24 (0.00%)
    1 / 13 (7.69%)
    0 / 41 (0.00%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    1
    0
    1
    0
    0
    0
    Sinusitis
         subjects affected / exposed
    3 / 78 (3.85%)
    2 / 24 (8.33%)
    0 / 13 (0.00%)
    1 / 41 (2.44%)
    1 / 43 (2.33%)
    1 / 22 (4.55%)
         occurrences all number
    3
    2
    0
    1
    1
    1
    Upper respiratory tract infection
         subjects affected / exposed
    4 / 78 (5.13%)
    0 / 24 (0.00%)
    2 / 13 (15.38%)
    2 / 41 (4.88%)
    4 / 43 (9.30%)
    2 / 22 (9.09%)
         occurrences all number
    4
    0
    2
    2
    4
    3
    Urinary tract infection
         subjects affected / exposed
    3 / 78 (3.85%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    3 / 41 (7.32%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    3
    0
    0
    3
    0
    0
    Metabolism and nutrition disorders
    Hypercalcaemia
         subjects affected / exposed
    3 / 78 (3.85%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    3 / 41 (7.32%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    3
    0
    0
    3
    0
    0
    Hyperglycaemia
         subjects affected / exposed
    0 / 78 (0.00%)
    0 / 24 (0.00%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    1 / 43 (2.33%)
    2 / 22 (9.09%)
         occurrences all number
    0
    0
    0
    0
    2
    3
    Hyperkalaemia
         subjects affected / exposed
    4 / 78 (5.13%)
    1 / 24 (4.17%)
    0 / 13 (0.00%)
    3 / 41 (7.32%)
    0 / 43 (0.00%)
    0 / 22 (0.00%)
         occurrences all number
    4
    1
    0
    3
    0
    0
    Hyperuricaemia
         subjects affected / exposed
    2 / 78 (2.56%)
    2 / 24 (8.33%)
    0 / 13 (0.00%)
    0 / 41 (0.00%)
    2 / 43 (4.65%)
    0 / 22 (0.00%)
         occurrences all number
    3
    3
    0
    0
    2
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Feb 2013
    Amendment 1 was applicable to all study sites that were required to include information from the Study Procedures Manual
    11 Dec 2013
    The main purpose of this amendment was to incorporate the recommendations related to HBV reactivation which were based on the update to internal global safety information for ofatumumab. Recommendations were given on HBV screening, monitoring and management for all subjects who a received ofatumumab and all subjects who completed treatment with ofatumumab in the previous 12 months before the amendment and were in the follow-up phase of the protocol.
    25 Feb 2016
    Change in study sponsorship from GSK to Novartis. Other clarifications have been included in this amendment: List of abbreviations from CRO to Clinical Research Organization, change in time Period and Frequency of Detecting AEs and SAEs, Prompt Reporting of Serious Adverse Events and Other Events to Novartis, Pregnancy Reporting, Study and Site Closure, record Retention, Provision of Study Results to Investigators, Posting of Information on Publically Available Clinical Trials Registers and Publication

    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.
    Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.novfor complete trial results.
    For support, Contact us.
    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
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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