Efficacy and Safety of Ofatumumab Retreatment and Maintenance Treatment in Patients With B-cell Chronic Lymphocytic Leukemia (CLL)

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00802737
• Collaborator: Genmab (Industry)
• Enrollment: 29
• Locations: 2
• Arm: 1
• Duration (Months): 51.9
• Patients Per Site: 14.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of the trial is to investigate the efficacy and safety of ofatumumab retreatment and maintenance in patients with chronic lymphocytic leukemia who have previously responded or had disease stabilization after ofatumumab in an ongoing trial (Hx-CD20-406).

Condition or Disease	Intervention/Treatment	Phase
Leukaemia, Lymphocytic, Chronic	Drug: Ofatumumab	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Single-arm, International, Multi-center Trial Investigating the Efficacy and Safety of Ofatumumab Retreatment and Maintenance in CLL Patients Who Progressed Following Response or Stable Disease After Ofatumumab Treatment in Hx-CD20-406
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: May 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ofatumumab Eight once weekly infusions (1 x 300 mg + 7 x 2000 mg), then 2000 mg once monthly for two years	Drug: Ofatumumab; Eight once weekly infusions (1 x 300 mg + 7 x 2000 mg), then 2000 mg once monthly for two years; Other Names: HuMax-CD20

Outcome Measures

Primary Outcome Measures

1. Number of Participants (Par.) Classified as Responders (Rs) and Non-responders (NRs) for Objective Response in Accordance With the National Cancer Institute Working Group (NCIWG) 1996 Guidelines [Start of treatment (Week 0/Visit 2) until Week 52]

   Par. with complete remission (CR), nodular partial remission (nPR), and partial remission (PR) on 2 consecutive visits >=56 days apart were classified as Rs; those with stable disease (SD)/progressive disease (PD) were classified as NRs. Per the NCIWG 1996 guidelines: CR; no lymphadenopathy/hepatomegaly/splenomegaly/constitutional symptoms, normal hematology, normocellular bone marrow sample for age, <30% lymphocytes (LC), no lymphoid nodule; PR: >=50% decrease in LC/lymphadenopathy; nPR: persistent bone marrow nodules; PD: new lesion or increase by >=50% from baseline; SD: no CR, PR, or PD.

Secondary Outcome Measures

1. Duration of Response [From the time of the initial response until progression or death (average of 14.1 study months)]

   Duration of response is defined as the time from the initial response (first visit at which response is observed) to progression or death. If the participant had progression between scheduled visits, no progression at the end of the trial, treatment discontinuation for undocumented progression, treatment discontinuation for toxicity or other reason, new anti-cancer treatment, and experienced death or progression after two or more missed visits in a row the endpoint was censored.

2. Progression-Free Survival (PFS) [Start of treatment (Week 0 of Visit 2) until progression or death (average of 14.1 study months)]

   PFS is defined as the time from randomization until progression (prog.)/death. Prog. events are defined by well-documented and verifiable data; other data are censored. If the par. had prog. between scheduled visits, died before the first assessment, or died between adequate visits, the endpoint was considered progressed. If there was no prog. at the end of the trial, treatment discontinuation for undocumented prog./toxicity/other reason, new anti-cancer treatment, and death/prog. after >=2 missed visits in a row, the endpoint was censored. Clinical prog. is not considered as a prog. endpoint.

3. Time to Next Chronic Lymphocytic Leukemia (CLL) Treatment [Time from start of study treatment (Week 0 of Visit 2) until the time of first administration of a CLL treatment other than ofatumumab (average of 14.8 study months)]

   Time to next chronic lymphocytic leukemia (CLL) treatment is defined as the time from treatment allocation/randomization (Visit 2) until the time of the first administration of the next CLL treatment other than ofatumumab (or HuMaxCD20, a fully human monoclonal antibody to CD20 that is expressed on the surface of B-cells).

4. Overall Survival (OS) [Time from start of study treatment (Week 0 of Visit 2) until date of death or time that participant was no longer followed (median of 18.0 months)]

   OS is defined as the time from allocation to death.

5. Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Month 4 [Baseline (Visit 2) and Month 4]

   Reduction in tumor size was measured as the percent change in the sum of the products of the diameters of the largest abnormal lymph nodes from Baseline to Week 24. Percent change was calculated as (Week 24 SPD minus Baseline SPD)/Baseline SPD * 100.

6. Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Month 12 [Baseline (Visit 2) and Month 12]

   Reduction in tumor size was measured by the percentage change in the sum of products of the diameters of the largest abnormal lymph nodes from Baseline to Month 12. Percent change was calculated as (Month 12 SPD minus Baseline SPD)/Baseline SPD * 100.

7. Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Month 24 [Baseline (Visit 2) and Month 24]

   Reduction in tumor size was measured by the percentage change in the sum of products of the diameters of the largest abnormal lymph nodes from Baseline to Month 24. Percent change was calculated as (Month 24 SPD minus Baseline SPD)/Baseline SPD * 100.

8. Number of Participants With Negative and Positive Human Anti-human Antibody (HAHA) Results at the Time of Screening and Post Ofatumumab [Screening and post ofatumumab (up to Study Month 32)]

   HAHAs are indicators of immunogenicity to ofatumumab. HAHA levels were assessed for each participant at the end of participation in the study (at their last visit). A positive HAHA status indicates a positive enzyme-linked immunosorbent assay (ELISA) result, an inconclusive status indicates a negative ELISA result at ofatumumab concentration above the threshold at which ofatumumab may interfere with the assay, and a negative status indicates a negative ELISA result at ofatumumab concentration below the threshold.

9. Number of Participants Who Experienced Any Adverse Event [From the first infusion (Visit 2/Week 0) until the last visit of the Extended Follow-up Phase (up to Study Month 26 [visit 34])]

   An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with the treatment. A list of AEs experienced in the study with a frequency threshold of 5% can be found in the AE section of this results record.

10. Number of Participants With the Indicated Major Infections [From the first infusion (Visit 2/Week 0) until the last visit of the Extended Follow-up Phase (up to Study Month 26 [visit 34])]

    The data collected for this analysis are reported in the overall Serious Adverse Events (SAEs) of infections rather than reported separately for this specific analysis. This is a conservative approach for reporting all infectious SAEs in order to ensure that all of the infectious SAEs are represented.

11. Number of Participants With Infections Requiring Hospitalization or Intravenous Antibiotics [From the first infusion (Visit 2/Week 0) until the last visit of the Extended Follow-up Phase (up to Study Month 26 [visit 34])]

    The data collected for this analysis are reported in the overall SAEs of infections rather than reported separately for this specific analysis. This is a conservative approach for reporting all infectious SAEs in order to ensure that all of the infectious SAEs are represented.

12. Cmax and Ctrough at Visit 2 (Week 0) and at Visit 14 (Month 4) [Visit 2 (Week 0) and Visit 14 (Month 4)]

    Cmax is defined as the maximum concentration of drug in plasma samples (collected at the end of the infusion). Ctrough is defined as the concentration of drug in plasma samples at the end of a dosing interval (collected directly before next administration). Ctrough before the first infusion represents residual ofatumumab from participation in Study Hx-CD20-406.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Has responded to ofatumumab treatment (CR, nPR, PR) or has had SD at least up to and including visit number 14 (24 weeks after first infusion) in the Hx-CD20-406 trial.

• Has disease progression after visit number 14 (24 weeks after first infusion) in the Hx CD20 406 trial.

• Received at least eight ofatumumab infusions.

• Has active CLL with an indication for treatment.

• Has Eastern Cooperative Oncology Group (ECOG) performance status grade 0, 1 or 2.

• Provides signed informed consent, following receipt of verbal and written information about the trial, before any trial related activity is carried out.

• If previously treated in GEN416 (this trial), the patient must have achieved CR with subsequent disease progression 24 weeks or later after the first infusion in the GEN416 trial.

Exclusion Criteria:

• The disease has transformed to more aggressive B-cell malignancies (e.g. diffuse large B-cell lymphoma, Richter's syndrome or prolymphocytic leukemia).

• Has a suspected treatment requiring malignancy other than CLL.

• Has received treatment other than ofatumumab within two weeks prior to visit 2.

• Has clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from visit 1, congestive heart failure (NYHA III IV), and arrhythmia requiring therapy, with the exception of clinically non-significant extra systoles or minor conduction abnormalities.

• Has significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease.

• Has a history of significant cerebrovascular disease.

• Is known HIV positive.

• Has positive serology for hepatitis B, defined as a positive test for HBsAg and/or positive tests for both anti-HBs and anti-HBc.

• Has known or suspected hypersensitivity to components of the IMP.

• Has received treatment with any non-marketed drug substance or experimental therapy other than ofatumumab within four weeks prior to visit 2.

• Currently participates in any other interventional clinical trial other than Hx-CD20-406.

• Known or suspected to not being able to comply with a trial protocol (e.g. due to alcoholism, drug dependency or psychiatric disorder).

• Is breast feeding (women only).

• Has a positive pregnancy test at screening (women only).

• Is not willing to use adequate contraception during the trial and one year after last dose of ofatumumab (women only). Adequate contraception is defined as hormonal birth control or intrauterine device. For patients in the US the use of double barrier method is considered adequate.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Stockholm		Sweden	SE-171 76
2	GSK Investigational Site	Örebro		Sweden	SE-701 85

Sponsors and Collaborators

• GlaxoSmithKline
• Genmab

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00802737
• Other Study ID Numbers: 111827; GEN416
• First Posted: Dec 5, 2008
• Last Update Posted: May 14, 2014
• Last Verified: Apr 1, 2014

• Keywords provided by GlaxoSmithKline: Maintenance; Retreatment; Chronic lymphocytic leukemia; B-Cell Chronic Lymphocytic Leukemia; Ofatumumab
• Additional relevant MeSH terms: Leukemia; Leukemia, Lymphoid; Leukemia, Lymphocytic, Chronic, B-Cell; Ofatumumab

Study Results

Participant Flow

Recruitment Details	Per study protocol
Pre-assignment Detail	Completed study Hx-CD20-406 (Study OMB111773; NCT00349349)

Arm/Group Title	2000 mg Ofatumumab + DR	2000 mg Ofatumumab + BFR	2000 mg Ofatumumab + Other
Arm/Group Description	Participants (Par.) who had responded to ofatumumab or had stable disease in Hx-CD20-406 (Study OMB111773; NCT00349349) and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as double refractory (DR), defined as participants who were enrolled in Study Hx-CD20-406 and were refractory to both fludarabine and alemtuzumab. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as bulky fludarabine refractory (BFR), defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).
Period Title: Overall Study
STARTED	17	11	1
COMPLETED	0	0	0
NOT COMPLETED	17	11	1

Baseline Characteristics

Arm/Group Title	2000 mg Ofatumumab + DR	2000 mg Ofatumumab + BFR	2000 mg Ofatumumab + Other	Total
Arm/Group Description	Participants (Par.) who had responded to ofatumumab or had stable disease in Hx-CD20-406 (Study OMB111773; NCT00349349) and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as double refractory (DR), defined as participants who were enrolled in Study Hx-CD20-406 and were refractory to both fludarabine and alemtuzumab. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as bulky fludarabine refractory (BFR), defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Total of all reporting groups
Overall Participants	17	11	1	29
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	64.8 (5.83)	66.9 (9.08)	84.0 (NA)	66.3 (7.85)
Sex: Female, Male (Count of Participants)
Female	4 23.5%	4 36.4%	1 100%	9 31%
Male	13 76.5%	7 63.6%	0 0%	20 69%
Race/Ethnicity, Customized (participants) [Number]
Asian	1 5.9%	0 0%	0 0%	1 3.4%
White	16 94.1%	11 100%	1 100%	28 96.6%

Outcome Measures

1. Primary Outcome

Title	Number of Participants (Par.) Classified as Responders (Rs) and Non-responders (NRs) for Objective Response in Accordance With the National Cancer Institute Working Group (NCIWG) 1996 Guidelines
Description	Par. with complete remission (CR), nodular partial remission (nPR), and partial remission (PR) on 2 consecutive visits >=56 days apart were classified as Rs; those with stable disease (SD)/progressive disease (PD) were classified as NRs. Per the NCIWG 1996 guidelines: CR; no lymphadenopathy/hepatomegaly/splenomegaly/constitutional symptoms, normal hematology, normocellular bone marrow sample for age, <30% lymphocytes (LC), no lymphoid nodule; PR: >=50% decrease in LC/lymphadenopathy; nPR: persistent bone marrow nodules; PD: new lesion or increase by >=50% from baseline; SD: no CR, PR, or PD.
Time Frame	Start of treatment (Week 0/Visit 2) until Week 52

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): all participants who had been exposed to study drug irrespective of their compliance to the planned course of treatment. Some participants were not evaluable (NE) due to participant withdraw, refusal, non-trial drug-related adverse events, and death.

Arm/Group Title	2000 mg Ofatumumab + DR	2000 mg Ofatumumab + BFR	2000 mg Ofatumumab + Other
Arm/Group Description	Participants (Par.) who had responded to ofatumumab or had stable disease in Hx-CD20-406 (Study OMB111773; NCT00349349) and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as double refractory (DR), defined as participants who were enrolled in Study Hx-CD20-406 and were refractory to both fludarabine and alemtuzumab. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as bulky fludarabine refractory (BFR), defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).
Measure Participants	17	11	1
Responders with CR	2 11.8%	0 0%	0 0%
Responders with nPR	0 0%	0 0%	0 0%
Responders with PR	2 11.8%	2 18.2%	1 100%
Non-responders with SD	8 47.1%	7 63.6%	0 0%
Non-responders with PD	3 17.6%	0 0%	0 0%
NE	2 11.8%	2 18.2%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	2000 mg Ofatumumab + DR
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	proportion of responders
	Estimated Value	0.24
	Confidence Interval	(2-Sided) 95%; 0.07 to 0.50
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% exact confidence intervals were calculated based on the binomial distribution. The estimated value was calculated using the number of responders (CR+nPR+PR) as the numerator and the total number of par. in the group as the denominator.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	2000 mg Ofatumumab + BFR
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	proportion of responders
	Estimated Value	0.18
	Confidence Interval	(2-Sided) 95%; 0.02 to 0.52
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% exact confidence intervals were calculated based on the binomial distribution. The estimated value was calculated using the number of responders (CR+nPR+PR) as the numerator and the total number of par. in the group as the denominator.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	2000 mg Ofatumumab + Other
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	proportion of responders
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.03 to 1.00
	Parameter Dispersion	Type: Value:
	Estimation Comments	Two-sided 95% exact confidence intervals were calculated based on the binomial distribution. The estimated value was calculated using the number of responders (CR+nPR+PR) as the numerator and the total number of par. in the group as the denominator.

2. Secondary Outcome

Title	Duration of Response
Description	Duration of response is defined as the time from the initial response (first visit at which response is observed) to progression or death. If the participant had progression between scheduled visits, no progression at the end of the trial, treatment discontinuation for undocumented progression, treatment discontinuation for toxicity or other reason, new anti-cancer treatment, and experienced death or progression after two or more missed visits in a row the endpoint was censored.
Time Frame	From the time of the initial response until progression or death (average of 14.1 study months)

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	2000 mg Ofatumumab + DR	2000 mg Ofatumumab + BFR	2000 mg Ofatumumab + Other
Arm/Group Description	Participants (Par.) who had responded to ofatumumab or had stable disease in Hx-CD20-406 (Study OMB111773; NCT00349349) and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as double refractory (DR), defined as participants who were enrolled in Study Hx-CD20-406 and were refractory to both fludarabine and alemtuzumab. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as bulky fludarabine refractory (BFR), defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).
Measure Participants	17	11	1
Median (95% Confidence Interval) [months]	NA	NA	NA

3. Secondary Outcome

Title	Progression-Free Survival (PFS)
Description	PFS is defined as the time from randomization until progression (prog.)/death. Prog. events are defined by well-documented and verifiable data; other data are censored. If the par. had prog. between scheduled visits, died before the first assessment, or died between adequate visits, the endpoint was considered progressed. If there was no prog. at the end of the trial, treatment discontinuation for undocumented prog./toxicity/other reason, new anti-cancer treatment, and death/prog. after >=2 missed visits in a row, the endpoint was censored. Clinical prog. is not considered as a prog. endpoint.
Time Frame	Start of treatment (Week 0 of Visit 2) until progression or death (average of 14.1 study months)

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	2000 mg Ofatumumab + DR	2000 mg Ofatumumab + BFR	2000 mg Ofatumumab + Other
Arm/Group Description	Participants (Par.) who had responded to ofatumumab or had stable disease in Hx-CD20-406 (Study OMB111773; NCT00349349) and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as double refractory (DR), defined as participants who were enrolled in Study Hx-CD20-406 and were refractory to both fludarabine and alemtuzumab. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as bulky fludarabine refractory (BFR), defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).
Measure Participants	17	11	1
Median (95% Confidence Interval) [months]	7.9	7.2	NA

4. Secondary Outcome

Title	Time to Next Chronic Lymphocytic Leukemia (CLL) Treatment
Description	Time to next chronic lymphocytic leukemia (CLL) treatment is defined as the time from treatment allocation/randomization (Visit 2) until the time of the first administration of the next CLL treatment other than ofatumumab (or HuMaxCD20, a fully human monoclonal antibody to CD20 that is expressed on the surface of B-cells).
Time Frame	Time from start of study treatment (Week 0 of Visit 2) until the time of first administration of a CLL treatment other than ofatumumab (average of 14.8 study months)

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	2000 mg Ofatumumab + DR	2000 mg Ofatumumab + BFR	2000 mg Ofatumumab + Other
Arm/Group Description	Participants (Par.) who had responded to ofatumumab or had stable disease in Hx-CD20-406 (Study OMB111773; NCT00349349) and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as double refractory (DR), defined as participants who were enrolled in Study Hx-CD20-406 and were refractory to both fludarabine and alemtuzumab. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as bulky fludarabine refractory (BFR), defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).
Measure Participants	17	11	1
Median (95% Confidence Interval) [months]	13.9	11.6	NA

5. Secondary Outcome

Title	Overall Survival (OS)
Description	OS is defined as the time from allocation to death.
Time Frame	Time from start of study treatment (Week 0 of Visit 2) until date of death or time that participant was no longer followed (median of 18.0 months)

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	2000 mg Ofatumumab + DR	2000 mg Ofatumumab + BFR	2000 mg Ofatumumab + Other
Arm/Group Description	Participants (Par.) who had responded to ofatumumab or had stable disease in Hx-CD20-406 (Study OMB111773; NCT00349349) and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as double refractory (DR), defined as participants who were enrolled in Study Hx-CD20-406 and were refractory to both fludarabine and alemtuzumab. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as bulky fludarabine refractory (BFR), defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).
Measure Participants	17	11	1
Median (95% Confidence Interval) [months]	27.6	11.3	12.3

6. Secondary Outcome

Title	Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Month 4
Description	Reduction in tumor size was measured as the percent change in the sum of the products of the diameters of the largest abnormal lymph nodes from Baseline to Week 24. Percent change was calculated as (Week 24 SPD minus Baseline SPD)/Baseline SPD * 100.
Time Frame	Baseline (Visit 2) and Month 4

Outcome Measure Data

Analysis Population Description

FAS. Measurement of tumor size was completed by physical examination for participants remaining in the study at Month 4. Only participants with a baseline value and a post-baseline value at Month 4 were included in the calculation.

Arm/Group Title	2000 mg Ofatumumab + DR	2000 mg Ofatumumab + BFR	2000 mg Ofatumumab + Other
Arm/Group Description	Participants (Par.) who had responded to ofatumumab or had stable disease in Hx-CD20-406 (Study OMB111773; NCT00349349) and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as double refractory (DR), defined as participants who were enrolled in Study Hx-CD20-406 and were refractory to both fludarabine and alemtuzumab. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as bulky fludarabine refractory (BFR), defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).
Measure Participants	8	6	1
Median (Full Range) [Percent change in tumor size]	-55.3	-64.8	0

7. Secondary Outcome

Title	Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Month 12
Description	Reduction in tumor size was measured by the percentage change in the sum of products of the diameters of the largest abnormal lymph nodes from Baseline to Month 12. Percent change was calculated as (Month 12 SPD minus Baseline SPD)/Baseline SPD * 100.
Time Frame	Baseline (Visit 2) and Month 12

Outcome Measure Data

Analysis Population Description

FAS. No participants in the 2000 mg Ofatumumab + Other treatment arm were able to contribute to this measure. Measurement of tumor size was completed by physical examination for participants remaining in the study at Month 12. Only participants with a baseline value and a post-baseline value at Month 12 were included in the calculation.

Arm/Group Title	2000 mg Ofatumumab + DR	2000 mg Ofatumumab + BFR	2000 mg Ofatumumab + Other
Arm/Group Description	Participants (Par.) who had responded to ofatumumab or had stable disease in Hx-CD20-406 (Study OMB111773; NCT00349349) and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as double refractory (DR), defined as participants who were enrolled in Study Hx-CD20-406 and were refractory to both fludarabine and alemtuzumab. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as bulky fludarabine refractory (BFR), defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).
Measure Participants	4	1	0
Median (Full Range) [Percent change in tumor size]	-65.2	-68.9

8. Secondary Outcome

Title	Median Percent Change of Tumor Size (Sum of Products Dimensions [SPD]) From Baseline (Visit 2) at Month 24
Description	Reduction in tumor size was measured by the percentage change in the sum of products of the diameters of the largest abnormal lymph nodes from Baseline to Month 24. Percent change was calculated as (Month 24 SPD minus Baseline SPD)/Baseline SPD * 100.
Time Frame	Baseline (Visit 2) and Month 24

Outcome Measure Data

Analysis Population Description

FAS. No participants in the 2000 mg Ofatumumab + Other treatment arm were able to contribute to this measure. Measurement of tumor size was completed by physical examination for participants remaining in the study at Month 24. Only participants with a baseline value and a post-baseline value at Month 24 were included in the calculation.

Arm/Group Title	2000 mg Ofatumumab + DR	2000 mg Ofatumumab + BFR	2000 mg Ofatumumab + Other
Arm/Group Description	Participants (Par.) who had responded to ofatumumab or had stable disease in Hx-CD20-406 (Study OMB111773; NCT00349349) and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as double refractory (DR), defined as participants who were enrolled in Study Hx-CD20-406 and were refractory to both fludarabine and alemtuzumab. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as bulky fludarabine refractory (BFR), defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).
Measure Participants	2	1	0
Median (Full Range) [Percent change in tumor size]	-83.3	-64.0

9. Secondary Outcome

Title	Number of Participants With Negative and Positive Human Anti-human Antibody (HAHA) Results at the Time of Screening and Post Ofatumumab
Description	HAHAs are indicators of immunogenicity to ofatumumab. HAHA levels were assessed for each participant at the end of participation in the study (at their last visit). A positive HAHA status indicates a positive enzyme-linked immunosorbent assay (ELISA) result, an inconclusive status indicates a negative ELISA result at ofatumumab concentration above the threshold at which ofatumumab may interfere with the assay, and a negative status indicates a negative ELISA result at ofatumumab concentration below the threshold.
Time Frame	Screening and post ofatumumab (up to Study Month 32)

Outcome Measure Data

Analysis Population Description

FAS. During the study, samples were to be taken at the last visit; however, this may not have been possible, such as in cases of death, or when the visit was not obvious as the "last visit." Therefore, some samples were not available or were not collected.

Arm/Group Title	2000 mg Ofatumumab + DR	2000 mg Ofatumumab + BFR	2000 mg Ofatumumab + Other	Total
Arm/Group Description	Participants (Par.) who had responded to ofatumumab or had stable disease in Hx-CD20-406 (Study OMB111773; NCT00349349) and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as double refractory (DR), defined as participants who were enrolled in Study Hx-CD20-406 and were refractory to both fludarabine and alemtuzumab. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as bulky fludarabine refractory (BFR), defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	This arm includes a total of all three arms combined.
Measure Participants	17	11	1	29
Screening, Positive, n=15 , 11, 1, 27	0 0%	0 0%	0 0%	0 0%
Screening, Inconclusive, n = 15 , 11 , 1, 27	5 29.4%	6 54.5%	0 0%	11 37.9%
Screening, Negative, n = 15 , 11 , 1, 27	10 58.8%	5 45.5%	1 100%	16 55.2%
Post-ofatumumab, Positive, n = 12 , 8 , 1, 21	0 0%	0 0%	0 0%	0 0%
Post-ofatumumab, Inconclusive, n=12 , 8, 1, 21	9 52.9%	8 72.7%	1 100%	18 62.1%
Post-ofatumumab, Negative, n =12 , 8, 1 , 21	3 17.6%	0 0%	0 0%	3 10.3%

10. Secondary Outcome

Title	Number of Participants Who Experienced Any Adverse Event
Description	An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with the treatment. A list of AEs experienced in the study with a frequency threshold of 5% can be found in the AE section of this results record.
Time Frame	From the first infusion (Visit 2/Week 0) until the last visit of the Extended Follow-up Phase (up to Study Month 26 [visit 34])

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	2000 mg Ofatumumab + DR	2000 mg Ofatumumab + BFR	2000 mg Ofatumumab + Other
Arm/Group Description	Participants (Par.) who had responded to ofatumumab or had stable disease in Hx-CD20-406 (Study OMB111773; NCT00349349) and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as double refractory (DR), defined as participants who were enrolled in Study Hx-CD20-406 and were refractory to both fludarabine and alemtuzumab. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as bulky fludarabine refractory (BFR), defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).
Measure Participants	17	11	1
Number [participants]	15 88.2%	11 100%	1 100%

11. Secondary Outcome

Title	Number of Participants With the Indicated Major Infections
Description	The data collected for this analysis are reported in the overall Serious Adverse Events (SAEs) of infections rather than reported separately for this specific analysis. This is a conservative approach for reporting all infectious SAEs in order to ensure that all of the infectious SAEs are represented.
Time Frame	From the first infusion (Visit 2/Week 0) until the last visit of the Extended Follow-up Phase (up to Study Month 26 [visit 34])

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	2000 mg Ofatumumab + DR	2000 mg Ofatumumab + BFR	2000 mg Ofatumumab + Other
Arm/Group Description	Participants (Par.) who had responded to ofatumumab or had stable disease in Hx-CD20-406 (Study OMB111773; NCT00349349) and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as double refractory (DR), defined as participants who were enrolled in Study Hx-CD20-406 and were refractory to both fludarabine and alemtuzumab. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as bulky fludarabine refractory (BFR), defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).
Measure Participants	0	0	0

12. Secondary Outcome

Title	Number of Participants With Infections Requiring Hospitalization or Intravenous Antibiotics
Description	The data collected for this analysis are reported in the overall SAEs of infections rather than reported separately for this specific analysis. This is a conservative approach for reporting all infectious SAEs in order to ensure that all of the infectious SAEs are represented.
Time Frame	From the first infusion (Visit 2/Week 0) until the last visit of the Extended Follow-up Phase (up to Study Month 26 [visit 34])

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	2000 mg Ofatumumab + DR	2000 mg Ofatumumab + BFR	2000 mg Ofatumumab + Other
Arm/Group Description	Participants (Par.) who had responded to ofatumumab or had stable disease in Hx-CD20-406 (Study OMB111773; NCT00349349) and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as double refractory (DR), defined as participants who were enrolled in Study Hx-CD20-406 and were refractory to both fludarabine and alemtuzumab. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as bulky fludarabine refractory (BFR), defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).
Measure Participants	0	0	0

13. Secondary Outcome

Title	Cmax and Ctrough at Visit 2 (Week 0) and at Visit 14 (Month 4)
Description	Cmax is defined as the maximum concentration of drug in plasma samples (collected at the end of the infusion). Ctrough is defined as the concentration of drug in plasma samples at the end of a dosing interval (collected directly before next administration). Ctrough before the first infusion represents residual ofatumumab from participation in Study Hx-CD20-406.
Time Frame	Visit 2 (Week 0) and Visit 14 (Month 4)

Outcome Measure Data

Analysis Population Description

FAS. Data are provided for the number of participants attending each visit. Participants withdrawn during the study were not analyzed.

Arm/Group Title	2000 mg Ofatumumab + DR	2000 mg Ofatumumab + BFR	2000 mg Ofatumumab + Other	Total
Arm/Group Description	Participants (Par.) who had responded to ofatumumab or had stable disease in Hx-CD20-406 (Study OMB111773; NCT00349349) and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as double refractory (DR), defined as participants who were enrolled in Study Hx-CD20-406 and were refractory to both fludarabine and alemtuzumab. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as bulky fludarabine refractory (BFR), defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).	Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).	This arm includes a total of all three arms combined.
Measure Participants	17	11	1	29
Cmax Visit 2, n= 16, 11, 1, 28	54.8	58.8	110	57.7
Cmax Visit 14, n= 8, 5, 0, 13	617	708	NA	651
Ctrough Visit 2, n= 16, 11, 1, 28	1.1	2.8	0.0	1.7
Ctrough Visit 14, n= 8, 5, 0, 13	42.6	59.5	NA	48.5

Adverse Events

Time Frame	On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the first dose of investigational product until the last visit of the Extended Follow-up Phase (up to Study Month 26 [visit 34]).
Adverse Event Reporting Description	SAEs and non-serious AEs were reported for members of the Safety Population, comprised of all participants randomized to treatment who received >=1 dose of trial medication.
Arm/Group Title	2000 mg Ofatumumab + DR		2000 mg Ofatumumab + BFR		2000 mg Ofatumumab + Other
Arm/Group Description	Participants (Par.) who had responded to ofatumumab or had stable disease in Hx-CD20-406 (Study OMB111773; NCT00349349) and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab intravenous (iv) infusion was initiated at 300 milligrams (mg), followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as double refractory (DR), defined as participants who were enrolled in Study Hx-CD20-406 and were refractory to both fludarabine and alemtuzumab. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).		Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions. For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up phase (Months 29-44). These participants were classified as bulky fludarabine refractory (BFR), defined as participants who were enrolled in the study and were refractory to fludarabine with bulky lymphadenopathy. Par. with disease progression entered into the Extended Follow-up phase (Months 47 to 62).		Participants who had responded to ofatumumab or had stable disease in Hx-CD20-406 and then progressed were offered retreatment and maintenance. For retreatment, ofatumumab iv infusion was initiated at 300 mg, followed by seven weekly 2000 mg infusions For the maintenance of responders, participants received 24 monthly infusions of 2000 mg for up to 24 months, for a total duration of treatment of up to 26 months after which, if possible, the par. entered the Follow-up (Months 29-44). These participants were classified as "other," defined as participants who were enrolled in the study but did not meet criteria for DR or BFR. Par. with disease progression entered the Extended Follow-up phase (Months 47 to 62).
All Cause Mortality
	2000 mg Ofatumumab + DR		2000 mg Ofatumumab + BFR		2000 mg Ofatumumab + Other
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	2000 mg Ofatumumab + DR		2000 mg Ofatumumab + BFR		2000 mg Ofatumumab + Other
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/17 (64.7%)		10/11 (90.9%)		1/1 (100%)
Blood and lymphatic system disorders
Neutropenia	3/17 (17.6%)		0/11 (0%)		0/1 (0%)
Haemolytic anaemia	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Lymphadenopathy	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Cardiac disorders
Atrial fibrillation	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Gastrointestinal disorders
Enteritis	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Diarrhea	1/17 (5.9%)		1/11 (9.1%)		0/1 (0%)
Inguinal hernia	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
General disorders
Disease progression	2/17 (11.8%)		1/11 (9.1%)		1/1 (100%)
Pyrexia	1/17 (5.9%)		1/11 (9.1%)		0/1 (0%)
Death	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Infections and infestations
Bronchopneumonia	2/17 (11.8%)		1/11 (9.1%)		0/1 (0%)
Pneumonia	1/17 (5.9%)		2/11 (18.2%)		0/1 (0%)
Candida pneumonia	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Herpes zoster	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Infection	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Lung infection pseudomonal	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Pneumocystis jiroveci pneumonia	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Rhinitis	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Sepsis	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Upper respiratory tract infection	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Urinary tract infection	0/17 (0%)		0/11 (0%)		1/1 (100%)
Infection Respiratory tract infection	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Respiratory tract infection fungal	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Injury, poisoning and procedural complications
Femoral neck fracture	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Investigations
Weight decreased	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Metabolism and nutrition disorders
Dehydration	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Chronic lympocytic leukaemia	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Chronic lymphocytic leukaemia refractory	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Melanoma, recurrent	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Malignant neoplasm of pleura	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Renal and urinary disorders
Renal failure	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Respiratory, thoracic and mediastinal disorders
Bronchiectasis	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Dyspnea	3/17 (17.6%)		0/11 (0%)		0/1 (0%)
Skin and subcutaneous tissue disorders
Rash	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Vascular disorders
Femoral artery occlusion	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Other (Not Including Serious) Adverse Events
	2000 mg Ofatumumab + DR		2000 mg Ofatumumab + BFR		2000 mg Ofatumumab + Other
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/17 (88.2%)		11/11 (100%)		1/1 (100%)
Blood and lymphatic system disorders
Anaemia	2/17 (11.8%)		1/11 (9.1%)		0/1 (0%)
Lymphopenia	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Splenomegaly	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Thrombocytopenia	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Neutropenia	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Cardiac disorders
Atrial fibrillation	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Ear and labyrinth disorders
Vertigo	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Eye disorders
Conjunctivitis	0/17 (0%)		1/11 (9.1%)		1/1 (100%)
Eyelid oedema	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Gastrointestinal disorders
Diarrhea	4/17 (23.5%)		5/11 (45.5%)		1/1 (100%)
Nausea	5/17 (29.4%)		2/11 (18.2%)		0/1 (0%)
Vomiting	4/17 (23.5%)		2/11 (18.2%)		0/1 (0%)
Abdominal pain	4/17 (23.5%)		1/11 (9.1%)		0/1 (0%)
Constipation	1/17 (5.9%)		3/11 (27.3%)		0/1 (0%)
Abdominal pain upper	1/17 (5.9%)		2/11 (18.2%)		0/1 (0%)
Dyspepsia	1/17 (5.9%)		1/11 (9.1%)		0/1 (0%)
Gingivitis	0/17 (0%)		2/11 (18.2%)		0/1 (0%)
Paraesthesia oral	1/17 (5.9%)		1/11 (9.1%)		0/1 (0%)
Abdominal distension	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Dry mouth	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Gastroesophageal reflux disease	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Hiatus hernia	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Mouth ulceration	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Oral pain	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Stomatitis	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Tongue blistering	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
General disorders
Chills	1/17 (5.9%)		4/11 (36.4%)		1/1 (100%)
Pyrexia	4/17 (23.5%)		3/11 (27.3%)		0/1 (0%)
Oedema peripheral	1/17 (5.9%)		3/11 (27.3%)		0/1 (0%)
Chest pain	2/17 (11.8%)		0/11 (0%)		0/1 (0%)
Fatigue	0/17 (0%)		2/11 (18.2%)		0/1 (0%)
Infusion site extravasation	0/17 (0%)		2/11 (18.2%)		0/1 (0%)
Asthenia	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Chest discomfort	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Influenza like illness	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Oedema	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Immune system disorders
Hypersensitivity	2/17 (11.8%)		0/11 (0%)		0/1 (0%)
Allergy to arthropod bite	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Infections and infestations
Bronchitis	2/17 (11.8%)		1/11 (9.1%)		0/1 (0%)
Furuncle	1/17 (5.9%)		1/11 (9.1%)		0/1 (0%)
Herpes zoster	1/17 (5.9%)		0/11 (0%)		1/1 (100%)
Infected bites	2/17 (11.8%)		0/11 (0%)		0/1 (0%)
Respiratory tract infection	1/17 (5.9%)		1/11 (9.1%)		0/1 (0%)
Upper respiratory tract infection	1/17 (5.9%)		1/11 (9.1%)		0/1 (0%)
Candidiasis	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Erysipelas	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Fungal infection	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Fungal skin infection	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Influenza	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Lower respiratory tract infection	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Lung infection	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Nasopharyngitis	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Oral herpes	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Rhinitis	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Skin infection	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Urinary tract infection	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Haemophilus infection	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Injury, poisoning and procedural complications
Contusion	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Humerus fracture	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Muscle strain	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Rib fracture	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Wound	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Investigations
C-Reactive protein increased	1/17 (5.9%)		1/11 (9.1%)		0/1 (0%)
Alanine aminotransferase increased	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Platelet count decreased	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Reticulocyte count increased	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Weight decreased	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Metabolism and nutrition disorders
Decreased appetite	2/17 (11.8%)		2/11 (18.2%)		0/1 (0%)
Hypokalaemia	2/17 (11.8%)		2/11 (18.2%)		0/1 (0%)
Cachexia	0/17 (0%)		1/11 (9.1%)		1/1 (100%)
Dehydration	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Hyperglycaemia	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Hypocalcaemia	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Hypophosphataemia	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Magnesium deficiency	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Musculoskeletal and connective tissue disorders
Back pains	3/17 (17.6%)		3/11 (27.3%)		0/1 (0%)
Arthralgia	2/17 (11.8%)		1/11 (9.1%)		0/1 (0%)
Muscle spasms	2/17 (11.8%)		1/11 (9.1%)		0/1 (0%)
Musculoskeletal chest pains	2/17 (11.8%)		0/11 (0%)		0/1 (0%)
Musculoskeletal pain	2/17 (11.8%)		0/11 (0%)		0/1 (0%)
Pain in extremity	1/17 (5.9%)		1/11 (9.1%)		0/1 (0%)
Joint swelling	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Squamous cell carcinoma of skin	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Basal cell carcinoma	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Nervous system disorders
Paraesthesia	0/17 (0%)		2/11 (18.2%)		0/1 (0%)
Dizziness	1/17 (5.9%)		1/11 (9.1%)		0/1 (0%)
Dizziness postural	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Headache	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Neuralgia	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Psychiatric disorders
Insomnia	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Anxiety	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Renal and urinary disorders
Dysuria	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Renal impairment	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Reproductive system and breast disorders
Vaginal haemorrhage	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	3/17 (17.6%)		4/11 (36.4%)		1/1 (100%)
Dyspnoea	1/17 (5.9%)		2/11 (18.2%)		0/1 (0%)
Chronic obstructive pulmonary disease	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Dysphonia	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Dyspnoea exertional	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Oropharyngeal pain	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Productive cough	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Rales	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Rhinorrhoea	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Sneezing	0/17 (0%)		1/11 (9.1%)		0/1 (0%)
Nasal polyps	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Upper respiratory tract congestion	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Skin and subcutaneous tissue disorders
Rash	3/17 (17.6%)		1/11 (9.1%)		0/1 (0%)
Hyperhidrosis	2/17 (11.8%)		1/11 (9.1%)		0/1 (0%)
Blister	0/17 (0%)		2/11 (18.2%)		0/1 (0%)
Eczema	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Pruritus	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Actinic keratosis	1/17 (5.9%)		0/11 (0%)		0/1 (0%)
Vascular disorders
Flushing	3/17 (17.6%)		1/11 (9.1%)		0/1 (0%)
Hypotension	1/17 (5.9%)		2/11 (18.2%)		0/1 (0%)
Hypertension	1/17 (5.9%)		1/11 (9.1%)		0/1 (0%)
Hot flush	0/17 (0%)		1/11 (9.1%)		0/1 (0%)

Limitations/Caveats

[Not Specified]

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Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.