Trial Outcomes & Findings for Long-term Efficacy and Safety of Repeated Ofatumumab Treatment Courses in RA Patients Who Previously Received Ofatumumab or Placebo in Trial Hx-CD20-403 (NCT NCT00655824)

Last Updated: 2017-12-05

Results Overview

Time to treatment withdrawal was defined as the time from the first infusion of ofatumumab until the date of treatment withdrawal. The sponsor discontinued the intravenous route of administration development program for rheumatoid arthritis (RA), and this study was terminated early; hence, this primary endpoint was not evaluated.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

124 participants

Primary outcome timeframe

From Baseline up to 144 weeks

Results posted on

2017-12-05

Participant Flow

Participants who previously participated in Study OFA112657 (NCT00291928) and who fulfilled the eligibility criteria were offered participation in this study (111752; NCT00655824).

A participant was considered to have completed the study when the Investigator decided that the participant had completed the treatment phase and recorded this in the Case Report Form. Completion was not based on having completed a set number of treatment courses.

Participant milestones

Participant milestones
Measure	Ofatumumab 700 mg IV Infusion Ofatumumab was administered in the dose of 700 milligrams (mg) as two intravenous (IV) infusions separated by 2 weeks for the first treatment course. The remaining treatment courses were given at individualized time intervals when a clinical response had been achieved following the previous treatment course and a subsequent worsening in disease activity had been observed. For the remaining treatment courses, the interval between the treatment courses was at least 16 weeks from the first infusion in the previous treatment course irrespective of progression in disease activity. After each treatment course, the participants attended their next trial visit 8 weeks after the first infusion of that course, followed by trial visits every 4 weeks up to Week 24, and subsequent visits every 8 weeks until the next treatment course. A maximum of 9 treatment courses were allowed.
Overall Study STARTED	92
Overall Study COMPLETED	8
Overall Study NOT COMPLETED	84

Reasons for withdrawal

Reasons for withdrawal
Measure	Ofatumumab 700 mg IV Infusion Ofatumumab was administered in the dose of 700 milligrams (mg) as two intravenous (IV) infusions separated by 2 weeks for the first treatment course. The remaining treatment courses were given at individualized time intervals when a clinical response had been achieved following the previous treatment course and a subsequent worsening in disease activity had been observed. For the remaining treatment courses, the interval between the treatment courses was at least 16 weeks from the first infusion in the previous treatment course irrespective of progression in disease activity. After each treatment course, the participants attended their next trial visit 8 weeks after the first infusion of that course, followed by trial visits every 4 weeks up to Week 24, and subsequent visits every 8 weeks until the next treatment course. A maximum of 9 treatment courses were allowed.
Overall Study Adverse Event	3
Overall Study Early Termination of Study by Sponsor	74
Overall Study Protocol Violation	1
Overall Study Withdrawal by Subject	4
Overall Study Deterioration of Trial Disease	2

Baseline Characteristics

Long-term Efficacy and Safety of Repeated Ofatumumab Treatment Courses in RA Patients Who Previously Received Ofatumumab or Placebo in Trial Hx-CD20-403

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ofatumumab 700 mg IV Infusion n=92 Participants Ofatumumab was administered in the dose of 700 milligrams (mg) as two intravenous (IV) infusions separated by 2 weeks for the first treatment course. The remaining treatment courses were given at individualized time intervals when a clinical response had been achieved following the previous treatment course and a subsequent worsening in disease activity had been observed. For the remaining treatment courses, the interval between the treatment courses was at least 16 weeks from the first infusion in the previous treatment course irrespective of progression in disease activity. After each treatment course, the participants attended their next trial visit 8 weeks after the first infusion of that course, followed by trial visits every 4 weeks up to Week 24, and subsequent visits every 8 weeks until the next treatment course. A maximum of 9 treatment courses were allowed.
Age, Continuous	52.9 Years STANDARD_DEVIATION 10.73 • n=5 Participants
Sex: Female, Male Female	84 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	92 participants n=5 Participants

PRIMARY outcome

Timeframe: From Baseline up to 144 weeks

Population: Full Analysis Set (FAS) Population: all participants who were exposed to study drug irrespective of their compliance to the planned course of treatment.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline (last visit prior to dosing in each TC) and last visit of each TC (8 wk post infusion, then every 4 wk until Wk 24; up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Population: FAS Population. One participant withdrew during the first infusion due to adverse events (AEs) of rash and pruritus. Only participants available at the indicated time point were assessed. Minimum change from baseline is defined as the smallest change at any visit over the course of Weeks 1 to 24 of each treatment cycle.

DAS28(ESR) is a numeric outcome that measures RA activity based on the ESR (a non-specific general indicator of inflammation), tender joint count (JC), swollen JC, and participant's global assessment of disease activity on a 100 millimeter Visual Analog Scale. DAS28 values range from 0 (no activity) and upwards; increasing values indicate increasing activity (there is no upper limit on the scale). Change from baseline (CFB) was calculated at all visits; however, minimum CFB was calculated as the minimum CFB obtained over the course of weeks 1-24 of each treatment cycle.

Outcome measures

Outcome measures
Measure	Ofatumumab 700 mg IV Infusion n=91 Participants Ofatumumab was administered in the dose of 700 milligrams (mg) as two intravenous (IV) infusions separated by 2 weeks for the first treatment course. The remaining treatment courses were given at individualized time intervals when a clinical response had been achieved following the previous treatment course and a subsequent worsening in disease activity had been observed. For the remaining treatment courses, the interval between the treatment courses was at least 16 weeks from the first infusion in the previous treatment course irrespective of progression in disease activity. After each treatment course, the participants attended their next trial visit 8 weeks after the first infusion of that course, followed by trial visits every 4 weeks up to Week 24, and subsequent visits every 8 weeks until the next treatment course. A maximum of 9 treatment courses were allowed.
Minimum Change From Baseline in Disease Activity Score Based on 28 Joints (DAS28) Over the Course of Weeks (Wk) 1 to 24 in Each Treatment Course (TC), Assessed by Erythrocyte Sedimentation Rate (ESR; Rate at Which Red Blood Cells Sediment in 1 Hour) Treatment Course 4, n=20	-1.65 scores on a scale Standard Deviation 1.110
Minimum Change From Baseline in Disease Activity Score Based on 28 Joints (DAS28) Over the Course of Weeks (Wk) 1 to 24 in Each Treatment Course (TC), Assessed by Erythrocyte Sedimentation Rate (ESR; Rate at Which Red Blood Cells Sediment in 1 Hour) Treatment Course 1, n=91	-1.92 scores on a scale Standard Deviation 0.918
Minimum Change From Baseline in Disease Activity Score Based on 28 Joints (DAS28) Over the Course of Weeks (Wk) 1 to 24 in Each Treatment Course (TC), Assessed by Erythrocyte Sedimentation Rate (ESR; Rate at Which Red Blood Cells Sediment in 1 Hour) Treatment Course 2, n=71	-1.58 scores on a scale Standard Deviation 0.824
Minimum Change From Baseline in Disease Activity Score Based on 28 Joints (DAS28) Over the Course of Weeks (Wk) 1 to 24 in Each Treatment Course (TC), Assessed by Erythrocyte Sedimentation Rate (ESR; Rate at Which Red Blood Cells Sediment in 1 Hour) Treatment Course 3, n=53	-1.52 scores on a scale Standard Deviation 0.849
Minimum Change From Baseline in Disease Activity Score Based on 28 Joints (DAS28) Over the Course of Weeks (Wk) 1 to 24 in Each Treatment Course (TC), Assessed by Erythrocyte Sedimentation Rate (ESR; Rate at Which Red Blood Cells Sediment in 1 Hour) Treatment Course 5, n=8	-2.16 scores on a scale Standard Deviation 1.114
Minimum Change From Baseline in Disease Activity Score Based on 28 Joints (DAS28) Over the Course of Weeks (Wk) 1 to 24 in Each Treatment Course (TC), Assessed by Erythrocyte Sedimentation Rate (ESR; Rate at Which Red Blood Cells Sediment in 1 Hour) Treatment Course 6, n=4	-0.87 scores on a scale Standard Deviation 0.771
Minimum Change From Baseline in Disease Activity Score Based on 28 Joints (DAS28) Over the Course of Weeks (Wk) 1 to 24 in Each Treatment Course (TC), Assessed by Erythrocyte Sedimentation Rate (ESR; Rate at Which Red Blood Cells Sediment in 1 Hour) Treatment Course 7, n=2	-2.10 scores on a scale Standard Deviation 2.146

SECONDARY outcome

Population: FAS Population. One participant withdrew during the first infusion due to AEs of rash and pruritis. Only participants available at the indicated time point were assessed.

DAS28(CRP) is a numeric outcome that measures RA activity based on the CRP (used to monitor acute inflammatory phases of RA), tender JC, swollen JC, and participant's global assessment of disease activity on a 100 millimeter Visual Analog Scale. DAS28 values range from 0 (no activity) and upwards; increasing values indicate increasing activity (there is no upper limit on the scale). Change from baseline (CFB) was calculated at all visits; however, minimum CFB was calculated as the minimum CFB obtained over the course of weeks 1-24 of each treatment cycle.

Outcome measures

Outcome measures
Measure	Ofatumumab 700 mg IV Infusion n=91 Participants Ofatumumab was administered in the dose of 700 milligrams (mg) as two intravenous (IV) infusions separated by 2 weeks for the first treatment course. The remaining treatment courses were given at individualized time intervals when a clinical response had been achieved following the previous treatment course and a subsequent worsening in disease activity had been observed. For the remaining treatment courses, the interval between the treatment courses was at least 16 weeks from the first infusion in the previous treatment course irrespective of progression in disease activity. After each treatment course, the participants attended their next trial visit 8 weeks after the first infusion of that course, followed by trial visits every 4 weeks up to Week 24, and subsequent visits every 8 weeks until the next treatment course. A maximum of 9 treatment courses were allowed.
Minimum Change From Baseline in DAS28 Over the Course of Weeks 1 to 24 in Each Treatment Course, Based on C-reactive Protein (CRP) Treatment Course 1, n=91	-1.79 scores on a scale Standard Deviation 0.906
Minimum Change From Baseline in DAS28 Over the Course of Weeks 1 to 24 in Each Treatment Course, Based on C-reactive Protein (CRP) Treatment Course 2, n=71	-1.32 scores on a scale Standard Deviation 0.771
Minimum Change From Baseline in DAS28 Over the Course of Weeks 1 to 24 in Each Treatment Course, Based on C-reactive Protein (CRP) Treatment Course 3, n=53	-1.27 scores on a scale Standard Deviation 0.793
Minimum Change From Baseline in DAS28 Over the Course of Weeks 1 to 24 in Each Treatment Course, Based on C-reactive Protein (CRP) Treatment Course 4, n=20	-1.55 scores on a scale Standard Deviation 0.970
Minimum Change From Baseline in DAS28 Over the Course of Weeks 1 to 24 in Each Treatment Course, Based on C-reactive Protein (CRP) Treatment Course 5, n=8	-1.88 scores on a scale Standard Deviation 1.181
Minimum Change From Baseline in DAS28 Over the Course of Weeks 1 to 24 in Each Treatment Course, Based on C-reactive Protein (CRP) Treatment Course 6, n=4	-0.88 scores on a scale Standard Deviation 0.572
Minimum Change From Baseline in DAS28 Over the Course of Weeks 1 to 24 in Each Treatment Course, Based on C-reactive Protein (CRP) Treatment Course 7, n=2	-2.14 scores on a scale Standard Deviation 1.893

SECONDARY outcome

Timeframe: Week 16 to Week 104 of each treatment course (up to 125 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Population: FAS Population. Only participants available at the indicated time point were assessed.

Time to re-treatment in each treatment course (TC) is defined as the time from the first infusion of ofatumumab until the date of the first infusion of the first re-treatment course. The data presented reflect the time to re-treatment, which is defined as the time in days between the first infusion of each TC and the first infusion of the following TC. For TC 1, time to re-treatment is defined as the time between the first infusion in TC 1 and the first infusion in TC 2; similarly, for TC 2 it is the time between the first infusion of TC 2 and the first infusion of TC 3. The study was terminated by the sponsor after Treatment Course 7; therefore, there are no re-treatment data available for Treatment Course 7.

Outcome measures

Outcome measures
Measure	Ofatumumab 700 mg IV Infusion n=73 Participants Ofatumumab was administered in the dose of 700 milligrams (mg) as two intravenous (IV) infusions separated by 2 weeks for the first treatment course. The remaining treatment courses were given at individualized time intervals when a clinical response had been achieved following the previous treatment course and a subsequent worsening in disease activity had been observed. For the remaining treatment courses, the interval between the treatment courses was at least 16 weeks from the first infusion in the previous treatment course irrespective of progression in disease activity. After each treatment course, the participants attended their next trial visit 8 weeks after the first infusion of that course, followed by trial visits every 4 weeks up to Week 24, and subsequent visits every 8 weeks until the next treatment course. A maximum of 9 treatment courses were allowed.
Time to Re-treatment in Each Treatment Course Treatment Course 1, n=73	291.01 days Standard Deviation 127.367
Time to Re-treatment in Each Treatment Course Treatment Course 2, n=53	328.83 days Standard Deviation 122.427
Time to Re-treatment in Each Treatment Course Treatment Course 3, n=20	235.95 days Standard Deviation 93.924
Time to Re-treatment in Each Treatment Course Treatment Course 4, n=8	154.88 days Standard Deviation 19.172
Time to Re-treatment in Each Treatment Course Treatment Course 5, n=4	161.75 days Standard Deviation 22.066
Time to Re-treatment in Each Treatment Course Treatment Course 6, n=2	120.00 days Standard Deviation 0.000

SECONDARY outcome

Timeframe: Before infusion and at the end of infusion for each Treatment Course (8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next TC; up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial vi

Population: FAS Population. Only participants with data available at the particular time points were analyzed.

Blood samples of participants were collected for the measurement of ofatumumab concentration in the blood. The blood samples were collected before infusion (BI) (baseline of that particular treatment course) and at the end of infusion (EI) of ofatumumab.

Outcome measures

Outcome measures
Measure	Ofatumumab 700 mg IV Infusion n=92 Participants Ofatumumab was administered in the dose of 700 milligrams (mg) as two intravenous (IV) infusions separated by 2 weeks for the first treatment course. The remaining treatment courses were given at individualized time intervals when a clinical response had been achieved following the previous treatment course and a subsequent worsening in disease activity had been observed. For the remaining treatment courses, the interval between the treatment courses was at least 16 weeks from the first infusion in the previous treatment course irrespective of progression in disease activity. After each treatment course, the participants attended their next trial visit 8 weeks after the first infusion of that course, followed by trial visits every 4 weeks up to Week 24, and subsequent visits every 8 weeks until the next treatment course. A maximum of 9 treatment courses were allowed.
Ofatumumab Serum Concentration Treatment Course 6, Baseline (EI); n=4	305474.8 Nanograms per milliliter (ng/mL) Standard Deviation 79304.73
Ofatumumab Serum Concentration Treatment Course 1, Baseline (BI); n=92	3596.3 Nanograms per milliliter (ng/mL) Standard Deviation 32324.08
Ofatumumab Serum Concentration Treatment Course 1, Baseline (EI); n=91	295588.3 Nanograms per milliliter (ng/mL) Standard Deviation 67754.65
Ofatumumab Serum Concentration Treatment Course 1, Week 104; n=1	NA Nanograms per milliliter (ng/mL) Standard Deviation NA The mean cannot be calculated for one participant. For this parameter at this time point, the value was below the lower limit of quantification.
Ofatumumab Serum Concentration Treatment Course 2, Baseline (BI); n=73	837.6 Nanograms per milliliter (ng/mL) Standard Deviation 3102.94
Ofatumumab Serum Concentration Treatment Course 2, Baseline (EI); n=92	292283.5 Nanograms per milliliter (ng/mL) Standard Deviation 87672.90
Ofatumumab Serum Concentration Treatment Course 2, Week 80; n=1	NA Nanograms per milliliter (ng/mL) Standard Deviation NA The mean cannot be calculated for one participant. For this parameter at this time point, the value was below the lower limit of quantification.
Ofatumumab Serum Concentration Treatment Course 3, Baseline (BI); n=53	955.0 Nanograms per milliliter (ng/mL) Standard Deviation 3270.64
Ofatumumab Serum Concentration Treatment Course 3, Baseline (EI); n=53	276719.3 Nanograms per milliliter (ng/mL) Standard Deviation 68620.07
Ofatumumab Serum Concentration Treatment Course 3, Week 64; n=1	NA Nanograms per milliliter (ng/mL) Standard Deviation NA The mean cannot be calculated for one participant. For this parameter at this time point, the value was below the lower limit of quantification.
Ofatumumab Serum Concentration Treatment Course 4, Baseline (BI); n=20	2070.2 Nanograms per milliliter (ng/mL) Standard Deviation 3329.24
Ofatumumab Serum Concentration Treatment Course 4, Baseline (EI); n=20	296305.7 Nanograms per milliliter (ng/mL) Standard Deviation 76863.21
Ofatumumab Serum Concentration Treatment Course 4, Week 40; n=1	NA Nanograms per milliliter (ng/mL) Standard Deviation NA The mean cannot be calculated for one participant. For this parameter at this time point, the value was below the lower limit of quantification.
Ofatumumab Serum Concentration Treatment Course 5, Baseline (BI); n=8	6077.8 Nanograms per milliliter (ng/mL) Standard Deviation 5853.91
Ofatumumab Serum Concentration Treatment Course 5, Baseline (EI); n=8	244302.0 Nanograms per milliliter (ng/mL) Standard Deviation 115157.71
Ofatumumab Serum Concentration Treatment Course 5, Week 24; n=2	6543.5 Nanograms per milliliter (ng/mL) Standard Deviation 1229.66
Ofatumumab Serum Concentration Treatment Course 6, Baseline (BI); n=4	5036.5 Nanograms per milliliter (ng/mL) Standard Deviation 3099.45
Ofatumumab Serum Concentration Treatment Course 6, Week 16; n=2	16661.5 Nanograms per milliliter (ng/mL) Standard Deviation 11651.00
Ofatumumab Serum Concentration Treatment Course 7, Baseline (BI); n=2	13262.0 Nanograms per milliliter (ng/mL) Standard Deviation 9702.92
Ofatumumab Serum Concentration Treatment Course 7, Baseline (EI); n=2	277168.5 Nanograms per milliliter (ng/mL) Standard Deviation 25532.92
Ofatumumab Serum Concentration Treatment Course 7, Week 8; n=2	73159.5 Nanograms per milliliter (ng/mL) Standard Deviation 19078.45

SECONDARY outcome

Timeframe: Baseline of each TC and 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Population: FAS Population

ACR20 is achieved if the participant has 20% improvement from Baseline in TJC and SJC and in 3 out of 5 of following assessments (A); participant pain A, participant global A, physician global A on a visual analog scale (VAS: a 10 cm scale ranging from "no pain" to "severe pain"; the distance marked by the participant from the "no pain" end is his joint pain score), participant self-assessed disability, and C-reactive protein. The sponsor discontinued the IV administration development program for RA, and this study was terminated early; hence, this endpoint was not evaluated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline of each TCand 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Timeframe: BI and PI A and B for all TCs (8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course [up to 156 weeks, follow-up phase]). TCs were individualized based on clinical status and may not correlate to trial visits/wk

Population: FAS Population. Only participants with data available at particular time points were analyzed.

The blood pressure (BP) of the participants was measured before infusion (infu) (BI) and post the first (A) and second (B) infusions (PI) during all 7 treatment courses.Timing for taking BP readings: SBP (BP when the heart is contracting): TC1, 2, 3 (infu A) more than 2 hours PI; TC1, 2 ,3 (infu B) 2 hours PI; TC4, 5, 6, 7 (infu A) 2 hours PI; TC4, 7 (infu B) 2 hours PI; TC5, 6 (infu B) 1 hour PI. For DBP (BP when the heart is resting between beats): TC1, 3 (infu A) more than 2 hours PI; TC2, 4, 5, 6, 7 (infu A) 2 hours PI; TC1, 2, 3, 4, 7 (infu A) 2 hours PI; TC5, 6 (infu B) 1 hour PI.

Outcome measures

Outcome measures
Measure	Ofatumumab 700 mg IV Infusion n=92 Participants Ofatumumab was administered in the dose of 700 milligrams (mg) as two intravenous (IV) infusions separated by 2 weeks for the first treatment course. The remaining treatment courses were given at individualized time intervals when a clinical response had been achieved following the previous treatment course and a subsequent worsening in disease activity had been observed. For the remaining treatment courses, the interval between the treatment courses was at least 16 weeks from the first infusion in the previous treatment course irrespective of progression in disease activity. After each treatment course, the participants attended their next trial visit 8 weeks after the first infusion of that course, followed by trial visits every 4 weeks up to Week 24, and subsequent visits every 8 weeks until the next treatment course. A maximum of 9 treatment courses were allowed.
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 1, BI-A, n =92	121.7 Millimeters of mercury (mmHg) Standard Deviation 18.20
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 1, PI-A, + >2 Hours, n=2	138.5 Millimeters of mercury (mmHg) Standard Deviation 3.54
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 1, BI-B, n=91	119.9 Millimeters of mercury (mmHg) Standard Deviation 18.38
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 1, PI-B, + 2 Hours, n=48	122.8 Millimeters of mercury (mmHg) Standard Deviation 13.22
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 2, BI-A, n=73	117.3 Millimeters of mercury (mmHg) Standard Deviation 16.84
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 2, PI-A, + 2 Hours, n=71	121.4 Millimeters of mercury (mmHg) Standard Deviation 13.86
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 2, BI-B, n=69	116.8 Millimeters of mercury (mmHg) Standard Deviation 16.09
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 2, PI-B, + 2 Hours, n=36	120.5 Millimeters of mercury (mmHg) Standard Deviation 13.52
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 3, BI-A, n=53	116.8 Millimeters of mercury (mmHg) Standard Deviation 15.61
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 3, PI-A, + >2 Hours, n=1	125.0 Millimeters of mercury (mmHg) Standard Deviation NA Standard deviation is not calculated when only one participant was analyzed.
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 3, BI-B, n=53	120.1 Millimeters of mercury (mmHg) Standard Deviation 15.59
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 3, PI-B, + 2 Hours, n=26	121.2 Millimeters of mercury (mmHg) Standard Deviation 9.63
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 4, BI-A, n=20	114.2 Millimeters of mercury (mmHg) Standard Deviation 14.86
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 4, PI-A, + 2 Hours, n=19	116.0 Millimeters of mercury (mmHg) Standard Deviation 12.54
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 4, BI-B, n=19	111.8 Millimeters of mercury (mmHg) Standard Deviation 14.86
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 4, PI-B, + 2 Hours, n=2	115.0 Millimeters of mercury (mmHg) Standard Deviation 15.56
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 5, BI-A, n=8	116.1 Millimeters of mercury (mmHg) Standard Deviation 16.17
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 5, PI-A, + 2 Hours, n=8	114.0 Millimeters of mercury (mmHg) Standard Deviation 11.99
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 5, BI-B, n=8	102.5 Millimeters of mercury (mmHg) Standard Deviation 12.54
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 5, PI-B, + 1 Hour, n=7	103.6 Millimeters of mercury (mmHg) Standard Deviation 14.35
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 6, BI-A, n=4	123.8 Millimeters of mercury (mmHg) Standard Deviation 7.50
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 6, PI-A, + 2 Hours, n=4	117.5 Millimeters of mercury (mmHg) Standard Deviation 12.58
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 6, BI-B, n=4	118.8 Millimeters of mercury (mmHg) Standard Deviation 13.15
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 6, PI-B, + 1 Hour, n=4	127.5 Millimeters of mercury (mmHg) Standard Deviation 2.89
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 7, BI-A, n=2	120.0 Millimeters of mercury (mmHg) Standard Deviation 14.14
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 7, PI-A, + 2 Hours, n=1	125.0 Millimeters of mercury (mmHg) Standard Deviation NA Standard deviation is not calculated when only one participant was analyzed.
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 7, BI-B, n=2	110.0 Millimeters of mercury (mmHg) Standard Deviation 0.00
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Treatment Course 7, PI-B, + 2 Hours, n=1	125.0 Millimeters of mercury (mmHg) Standard Deviation NA Standard deviation is not calculated when only one participant was analyzed.
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 1, BI-A, n=92	76.3 Millimeters of mercury (mmHg) Standard Deviation 11.51
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 1, PI-A, +>2 Hours, n=90	86.5 Millimeters of mercury (mmHg) Standard Deviation 6.36
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 1, BI-B, n=91	74.4 Millimeters of mercury (mmHg) Standard Deviation 11.85
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 1, PI-B, + 2 Hours, n=48	75.5 Millimeters of mercury (mmHg) Standard Deviation 8.73
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 2, BI-A, n=73	73.4 Millimeters of mercury (mmHg) Standard Deviation 10.26
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 2, PI-A, + 2 Hours, n=71	74.8 Millimeters of mercury (mmHg) Standard Deviation 8.56
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 2, BI-B, n=69	72.8 Millimeters of mercury (mmHg) Standard Deviation 10.37
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 2, PI-B, + 2 Hours, n=36	74.0 Millimeters of mercury (mmHg) Standard Deviation 7.58
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 3, BI-A, n=53	72.1 Millimeters of mercury (mmHg) Standard Deviation 10.84
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 3, PI-A, >2 Hours, n=1	75.0 Millimeters of mercury (mmHg) Standard Deviation NA Standard deviation is not calculated when only one participant was analyzed.
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 3, BI-B, n=53	74.7 Millimeters of mercury (mmHg) Standard Deviation 10.53
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 3, PI-B, + 2 Hours, n=26	75.3 Millimeters of mercury (mmHg) Standard Deviation 8.02
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 4, BI-A, n=20	71.7 Millimeters of mercury (mmHg) Standard Deviation 11.59
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 4, PI-A, + 2 Hours, n=19	75.1 Millimeters of mercury (mmHg) Standard Deviation 9.79
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 4, BI-B, n=19	71.7 Millimeters of mercury (mmHg) Standard Deviation 10.87
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 4, PI-B, + 2 Hours, n=2	75.0 Millimeters of mercury (mmHg) Standard Deviation 7.07
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 5, BI-A, n=8	74.6 Millimeters of mercury (mmHg) Standard Deviation 12.06
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 5, PI-A, + 2 Hours, n=8	77.5 Millimeters of mercury (mmHg) Standard Deviation 10.00
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 5, BI-B, n=8	68.4 Millimeters of mercury (mmHg) Standard Deviation 6.74
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 5, PI-B, +1 Hour, n=7	69.7 Millimeters of mercury (mmHg) Standard Deviation 10.44
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 6, BI-A, n=4	77.5 Millimeters of mercury (mmHg) Standard Deviation 6.45
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 6, PI-A, + 2 Hours, n=4	78.8 Millimeters of mercury (mmHg) Standard Deviation 4.79
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 6, BI-B, n=4	68.8 Millimeters of mercury (mmHg) Standard Deviation 10.31
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 6, PI-B, 1 Hour, n=4	81.3 Millimeters of mercury (mmHg) Standard Deviation 2.50
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 7, BI-A, n=2	85.0 Millimeters of mercury (mmHg) Standard Deviation 7.07
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 7, PI-A, + 2 Hours, n=1	90.0 Millimeters of mercury (mmHg) Standard Deviation NA Standard deviation is not calculated when only one participant was analyzed.
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 7, BI-B, n=2	75.0 Millimeters of mercury (mmHg) Standard Deviation 7.07
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Treatment Course 7, PI-B, + 2 Hours, n=1	90.0 Millimeters of mercury (mmHg) Standard Deviation NA Standard deviation is not calculated when only one participant was analyzed.
Assessment of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Follow-up, n=78	76.9 Millimeters of mercury (mmHg) Standard Deviation 9.16

SECONDARY outcome

Population: FAS Population. Only participants with data available at particular time points were analyzed.

The HR of the participants was measured to assess the condition of the heart.HR was measured BI and post the first (A) and second (B) infusins during all 7 treatment courses.Timing for measuring HR: TC1, 3 (infu A) more than 2 hours PI; TC1, 2 ,3, 4, 7 (infu B) 2 hours PI; TC2, 4, 5, 6, 7 (infu A) 2 hours PI; TC5, 6 (infu B) 1 hour PI.

Outcome measures

Outcome measures
Measure	Ofatumumab 700 mg IV Infusion n=92 Participants Ofatumumab was administered in the dose of 700 milligrams (mg) as two intravenous (IV) infusions separated by 2 weeks for the first treatment course. The remaining treatment courses were given at individualized time intervals when a clinical response had been achieved following the previous treatment course and a subsequent worsening in disease activity had been observed. For the remaining treatment courses, the interval between the treatment courses was at least 16 weeks from the first infusion in the previous treatment course irrespective of progression in disease activity. After each treatment course, the participants attended their next trial visit 8 weeks after the first infusion of that course, followed by trial visits every 4 weeks up to Week 24, and subsequent visits every 8 weeks until the next treatment course. A maximum of 9 treatment courses were allowed.
Assessment of Heart Rate (HR) HR, Treatment Course 4, PI-B, + 2 Hours, n=2	76.0 Beats per minute (bpm) Standard Deviation 5.66
Assessment of Heart Rate (HR) HR, Treatment Course 1, BI-A, n=92	73.4 Beats per minute (bpm) Standard Deviation 10.10
Assessment of Heart Rate (HR) HR, Treatment Course 1, PI-A, + >2 Hours, n=2	76.5 Beats per minute (bpm) Standard Deviation 12.02
Assessment of Heart Rate (HR) HR, Treatment Course 1, BI-B, n=91	71.8 Beats per minute (bpm) Standard Deviation 9.41
Assessment of Heart Rate (HR) HR, Treatment Course 1, PI-B, + 2 Hours, n=48	74.9 Beats per minute (bpm) Standard Deviation 10.72
Assessment of Heart Rate (HR) HR, Treatment Course 2, BI-A, n=73	70.9 Beats per minute (bpm) Standard Deviation 7.37
Assessment of Heart Rate (HR) HR, Treatment Course 2, PI-A, + 2 Hours, n=71	74.3 Beats per minute (bpm) Standard Deviation 7.88
Assessment of Heart Rate (HR) HR, Treatment Course 2, BI-B, n=69	72.9 Beats per minute (bpm) Standard Deviation 8.02
Assessment of Heart Rate (HR) HR, Treatment Course 2, PI-B, + 2 Hours, n=36	73.4 Beats per minute (bpm) Standard Deviation 7.53
Assessment of Heart Rate (HR) HR, Treatment Course 3, BI-A, n=53	72.6 Beats per minute (bpm) Standard Deviation 6.99
Assessment of Heart Rate (HR) HR, Treatment Course 3, PI-A, + >2 Hours, n= 1	68.0 Beats per minute (bpm) Standard Deviation NA Standard deviation is not calculated when only one participant was analyzed.
Assessment of Heart Rate (HR) HR, Treatment Course 3, BI-B, n=53	72.2 Beats per minute (bpm) Standard Deviation 8.57
Assessment of Heart Rate (HR) HR, Treatment Course 3, PI-B, + 2 Hours, n=26	75.6 Beats per minute (bpm) Standard Deviation 6.11
Assessment of Heart Rate (HR) HR, Treatment Course 4, BI-A, n=20	70.8 Beats per minute (bpm) Standard Deviation 5.77
Assessment of Heart Rate (HR) HR, Treatment Course 4, PI-A, + 2 Hours, n=19	74.6 Beats per minute (bpm) Standard Deviation 6.50
Assessment of Heart Rate (HR) HR, Treatment Course 4, BI-B, n=19	70.5 Beats per minute (bpm) Standard Deviation 4.43
Assessment of Heart Rate (HR) HR, Treatment Course 5, BI-A, n=8	70.9 Beats per minute (bpm) Standard Deviation 3.00
Assessment of Heart Rate (HR) HR, Treatment Course 5, PI-A, + 2 Hours, n=8	72.6 Beats per minute (bpm) Standard Deviation 3.66
Assessment of Heart Rate (HR) HR, Treatment Course 5, BI-B, n=8	68.9 Beats per minute (bpm) Standard Deviation 4.58
Assessment of Heart Rate (HR) HR, Treatment Course 5, PI-B, + 1 Hour, n=7	71.7 Beats per minute (bpm) Standard Deviation 4.96
Assessment of Heart Rate (HR) HR, Treatment Course 6, BI-A, n=4	70.0 Beats per minute (bpm) Standard Deviation 4.00
Assessment of Heart Rate (HR) HR, Treatment Course 6, PI-A, + 2 Hours, n=4	71.0 Beats per minute (bpm) Standard Deviation 6.00
Assessment of Heart Rate (HR) HR, Treatment Course 6, BI-B, n=4	68.0 Beats per minute (bpm) Standard Deviation 5.66
Assessment of Heart Rate (HR) HR, Treatment Course 6, PI-B, + 1 Hour, n=4	72.0 Beats per minute (bpm) Standard Deviation 0.00
Assessment of Heart Rate (HR) HR, Treatment Course 7, BI-A, n=2	72.0 Beats per minute (bpm) Standard Deviation 0.00
Assessment of Heart Rate (HR) HR, Treatment Course 7, PI-A, + 2 Hours, n=1	72.0 Beats per minute (bpm) Standard Deviation NA Standard deviation is not calculated when only one participant was analyzed.
Assessment of Heart Rate (HR) HR, Treatment Course 7, BI-B, n=2	70.0 Beats per minute (bpm) Standard Deviation 2.83
Assessment of Heart Rate (HR) HR, Treatment Course 7, PI-B, + 2 Hours, n=1	68.0 Beats per minute (bpm) Standard Deviation NA Standard deviation is not calculated when only one participant was analyzed.
Assessment of Heart Rate (HR) HR, Follow-up, n=78	72.1 Beats per minute (bpm) Standard Deviation 8.05

SECONDARY outcome

Population: FAS Population. Only participants with data available at particular time points were analyzed.

The BT of the participants was measured BI and post the first (A) and second (B) infusions (PI) of each cycle to assess the effect of ofatumumab on the BT.The BT of the participants was measured before BI and PI A and B during all 7 treatment courses.Timing for taking BT reading: TC1, 3 (infu A) more than 2 hours PI; TC1, 2 ,3, 4, 7 (infu B) 2 hours PI; TC2, 4, 5, 6, 7 (infu A) 2 hours PI; TC5, 6 (infu B) 1 hour PI.

Outcome measures

Outcome measures
Measure	Ofatumumab 700 mg IV Infusion n=92 Participants Ofatumumab was administered in the dose of 700 milligrams (mg) as two intravenous (IV) infusions separated by 2 weeks for the first treatment course. The remaining treatment courses were given at individualized time intervals when a clinical response had been achieved following the previous treatment course and a subsequent worsening in disease activity had been observed. For the remaining treatment courses, the interval between the treatment courses was at least 16 weeks from the first infusion in the previous treatment course irrespective of progression in disease activity. After each treatment course, the participants attended their next trial visit 8 weeks after the first infusion of that course, followed by trial visits every 4 weeks up to Week 24, and subsequent visits every 8 weeks until the next treatment course. A maximum of 9 treatment courses were allowed.
Assessment of Body Temperature (BT) BT, Treatment Course 1, BI-B, n=91	36.46 Degrees celcius Standard Deviation 0.368
Assessment of Body Temperature (BT) BT, Treatment Course 1, PI-B, + 2 Hours, n=48	36.53 Degrees celcius Standard Deviation 0.316
Assessment of Body Temperature (BT) BT, Treatment Course 2 BI-A, n=73	36.48 Degrees celcius Standard Deviation 0.313
Assessment of Body Temperature (BT) BT, Treatment Course 2 PI-A, + 2 Hours, n=71	36.56 Degrees celcius Standard Deviation 0.261
Assessment of Body Temperature (BT) BT, Treatment Course 2 BI-B, n=69	36.54 Degrees celcius Standard Deviation 0.370
Assessment of Body Temperature (BT) BT, Treatment Course 2 PI-B, + 2 Hours, n=36	36.58 Degrees celcius Standard Deviation 0.252
Assessment of Body Temperature (BT) BT, Treatment Course 3 BI-A, n=53	36.46 Degrees celcius Standard Deviation 0.307
Assessment of Body Temperature (BT) BT, Treatment Course 3 PI-A, + >2 Hours, n=1	36.60 Degrees celcius Standard Deviation NA Standard deviation is not calculated when only one participant was analyzed.
Assessment of Body Temperature (BT) BT, Treatment Course 3, BI-B, n=53	36.45 Degrees celcius Standard Deviation 0.392
Assessment of Body Temperature (BT) BT, Treatment Course 3, PI-B, + 2 Hours, n=26	36.59 Degrees celcius Standard Deviation 0.294
Assessment of Body Temperature (BT) BT, Treatment Course 4, BI-A, n=20	36.50 Degrees celcius Standard Deviation 0.381
Assessment of Body Temperature (BT) BT, Treatment Course 4, PI-A, + 2 Hours, n=19	36.58 Degrees celcius Standard Deviation 0.242
Assessment of Body Temperature (BT) BT, Treatment Course 4, BI-B, n=19	36.53 Degrees celcius Standard Deviation 0.421
Assessment of Body Temperature (BT) BT, Treatment Course 4, PI-B, + 2 Hours, n=2	37.00 Degrees celcius Standard Deviation 0.283
Assessment of Body Temperature (BT) BT, Treatment Course 5, BI-A, n=8	36.40 Degrees celcius Standard Deviation 0.267
Assessment of Body Temperature (BT) BT, Treatment Course 5, PI-A, + 2 Hours, n=8	36.50 Degrees celcius Standard Deviation 0.262
Assessment of Body Temperature (BT) BT, Treatment Course 5, BI-B, n=8	36.41 Degrees celcius Standard Deviation 0.242
Assessment of Body Temperature (BT) BT, Treatment Course 5, PI-B, + 1 Hour, n=7	36.49 Degrees celcius Standard Deviation 0.329
Assessment of Body Temperature (BT) BT, Treatment Course 6, BI-A, n=4	36.48 Degrees celcius Standard Deviation 0.126
Assessment of Body Temperature (BT) BT, Treatment Course 6, PI-A, + 2 Hours, n=4	36.48 Degrees celcius Standard Deviation 0.250
Assessment of Body Temperature (BT) BT, Treatment Course 6, BI-B, n=4	36.35 Degrees celcius Standard Deviation 0.370
Assessment of Body Temperature (BT) BT, Treatment Course 6, PI-B, + 1 Hour, n=4	36.45 Degrees celcius Standard Deviation 0.370
Assessment of Body Temperature (BT) BT, Treatment Course 7, BI-A, n=2	36.55 Degrees celcius Standard Deviation 0.071
Assessment of Body Temperature (BT) BT, Treatment Course 7, PI-A, + 2 Hours, n=1	36.60 Degrees celcius Standard Deviation NA Standard deviation is not calculated when only one participant was analyzed.
Assessment of Body Temperature (BT) BT, Treatment Course 7, BI-B, n=2	36.65 Degrees celcius Standard Deviation 0.071
Assessment of Body Temperature (BT) BT, Treatment Course 7, PI-B, + 2 Hours, n=1	36.60 Degrees celcius Standard Deviation NA Standard deviation is not calculated when only one participant was analyzed.
Assessment of Body Temperature (BT) BT, Follow-up, n=78	36.57 Degrees celcius Standard Deviation 0.323
Assessment of Body Temperature (BT) BT, Treatment Course 1, BI-A, n=92	36.50 Degrees celcius Standard Deviation 0.360
Assessment of Body Temperature (BT) BT, Treatment Course 1, PI-A, + >2 Hours, n=1	36.50 Degrees celcius Standard Deviation NA Standard deviation is not calculated when only one participant was analyzed.

SECONDARY outcome

Timeframe: 8 wk post infusion, then every 4 wk until Wk 24, then every 8 wk until next treatment course (up to 144 weeks). TCs were individualized based on clinical status and may not correlate to trial visits or study weeks.

Population: FAS Population. Only participants with data available at particular time points were analyzed.

Blood samples of participants were collected to assess LDH and CPK. Both tests are performed to evaluate the injury and damage to the body tissue, potentially from B-cell lysis.

Outcome measures

Outcome measures
Measure	Ofatumumab 700 mg IV Infusion n=92 Participants Ofatumumab was administered in the dose of 700 milligrams (mg) as two intravenous (IV) infusions separated by 2 weeks for the first treatment course. The remaining treatment courses were given at individualized time intervals when a clinical response had been achieved following the previous treatment course and a subsequent worsening in disease activity had been observed. For the remaining treatment courses, the interval between the treatment courses was at least 16 weeks from the first infusion in the previous treatment course irrespective of progression in disease activity. After each treatment course, the participants attended their next trial visit 8 weeks after the first infusion of that course, followed by trial visits every 4 weeks up to Week 24, and subsequent visits every 8 weeks until the next treatment course. A maximum of 9 treatment courses were allowed.
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) LDH, Treatment Course 7, Week 8, n=2	190.0 U/L Standard Deviation 25.46
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) CPK, Treatment Course 1, Baseline, n=92	61.4 U/L Standard Deviation 29.25
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) CPK, Treatment Course 2, Week 80, n=1	61.0 U/L Standard Deviation NA Standard deviation is not calculated when only one participant was analyzed.
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) CPK, Treatment Course 3, Baseline, n=53	77.7 U/L Standard Deviation 50.86
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) CPK, Treatment Course 3, Week 64, n=1	81.0 U/L Standard Deviation NA Standard deviation is not calculated when only one participant was analyzed.
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) CPK, Treatment Course 4, Baseline n=20	85.4 U/L Standard Deviation 64.46
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) CPK, Treatment Course 7, Baseline, n=2	103.0 U/L Standard Deviation 19.80
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) CPK, Treatment Course 7, Week 8, n=2	109.0 U/L Standard Deviation 15.56
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) CPK, Follow-up Week 12, n=59	79.3 U/L Standard Deviation 38.73
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) CPK, Follow-up Week 24, n=18	77.0 U/L Standard Deviation 26.09
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) LDH, Treatment Course 1, Baseline, n=92	189.6 U/L Standard Deviation 35.18
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) LDH, Treatment Course 1, Week 104, n=1	229.0 U/L Standard Deviation NA Standard deviation is not calculated when only one participant was analyzed.
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) LDH, Treatment Course 2, Baseline, n=73	198.6 U/L Standard Deviation 77.62
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) LDH, Treatment Course 2, Week 80, n=1	219.0 U/L Standard Deviation NA Standard deviation is not calculated when only one participant was analyzed.
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) LDH, Treatment Course 3, Baseline, n=53	186.5 U/L Standard Deviation 37.39
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) LDH, Treatment Course 3, Week 64, n=1	242.0 U/L Standard Deviation NA Standard deviation is not calculated when only one participant was analyzed.
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) LDH, Treatment Course 4, Baseline, n=20	184.6 U/L Standard Deviation 35.52
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) LDH, Treatment Course 4, Week 40, n=1	170.0 U/L Standard Deviation NA Standard deviation is not calculated when only one participant was analyzed.
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) LDH, Treatment Course 5, Baseline, n=8	179.4 U/L Standard Deviation 25.03
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) LDH, Treatment Course 5, Week 24, n=2	168.5 U/L Standard Deviation 27.58
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) LDH, Treatment Course 6, Baseline, n=4	173.3 U/L Standard Deviation 15.13
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) LDH, Treatment Course 6, Week 16, n=2	234.0 U/L Standard Deviation 53.74
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) LDH, Treatment Course 7, Baseline, n=2	292.0 U/L Standard Deviation 140.01
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) CPK, Treatment Course 1, Week 104, n=1	127.0 U/L Standard Deviation NA Standard deviation is not calculated when only one participant was analyzed.
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) CPK, Treatment Course 2, Baseline, n=73	70.5 U/L Standard Deviation 31.07
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) CPK, Treatment Course 4, Week 40, n=1	52.0 U/L Standard Deviation NA Standard deviation is not calculated when only one participant was analyzed.
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) CPK, Treatment Course 5, Baseline, n=8	157.6 U/L Standard Deviation 216.71
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) CPK, Treatment Course 5, Week 24, n=2	82.5 U/L Standard Deviation 27.58
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) CPK, Treatment Course 6, Baseline, n=4	84.8 U/L Standard Deviation 23.91
Assessment of Lactic Dehydrogenase (LDH) and Creatine Phosphokinase (CPK) CPK, Treatment Course 6, Week 16, n=2	100.0 U/L Standard Deviation 14.14

SECONDARY outcome

Population: FAS Population. Only participants with data available at particular time points were analyzed.

Electrocardiograms of the participants were taken. The abnormal clinically significant (CS) and not clinically significant (NCS) reading, as determined by the Investigator, were recorded.

Outcome measures

Outcome measures
Measure	Ofatumumab 700 mg IV Infusion n=92 Participants Ofatumumab was administered in the dose of 700 milligrams (mg) as two intravenous (IV) infusions separated by 2 weeks for the first treatment course. The remaining treatment courses were given at individualized time intervals when a clinical response had been achieved following the previous treatment course and a subsequent worsening in disease activity had been observed. For the remaining treatment courses, the interval between the treatment courses was at least 16 weeks from the first infusion in the previous treatment course irrespective of progression in disease activity. After each treatment course, the participants attended their next trial visit 8 weeks after the first infusion of that course, followed by trial visits every 4 weeks up to Week 24, and subsequent visits every 8 weeks until the next treatment course. A maximum of 9 treatment courses were allowed.
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 1, Week 24, Normal	64 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 3, Week 24, Normal	24 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 3, Week 24, Abnormal NCS	4 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 3, Week 56, Normal	1 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 3, Week 56, Abnormal NCS	1 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 3, Week 56, Abnormal CS	0 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 4, Week 24, Normal	7 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 4, Week 24, Abnormal NCS	0 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 5, Week 24, Abnormal NCS	0 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 5, Week 24, Abnormal CS	0 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 1, Week 24, Abnormal NCS	9 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 1, Week 24, Abnormal CS	0 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 1, Week 104, Normal	1 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 1, Week 104, Abnormal NCS	0 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 1, Week 104, Abnormal CS	0 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 2, Week 24, Normal	43 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 2, Week 24, Abnormal NCS	17 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 2, Week 24, Abnormal CS	0 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 2, Week 80, Normal	1 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 2, Week 80, Abnormal NCS	0 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 2, Week 80, Abnormal CS	0 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 4, Week 24, Abnormal CS	0 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 4, Week 32, Normal	3 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 4, Week 32, Abnormal NCS	0 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 4, Week 32, Abnormal CS	0 participants
Number of Participants With Normal and Abnormal Electrocardiogram Readings Treatment Course 5, Week 24, Normal	2 participants

Adverse Events

Ofatumumab 700 mg IV Infusion

Serious events: 11 serious events

Other events: 70 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Ofatumumab 700 mg IV Infusion n=92 participants at risk Ofatumumab was administered in the dose of 700 milligrams (mg) as two intravenous (IV) infusions separated by 2 weeks for the first treatment course. The remaining treatment courses were given at individualized time intervals when a clinical response had been achieved following the previous treatment course and a subsequent worsening in disease activity had been observed. For the remaining treatment courses, the interval between the treatment courses was at least 16 weeks from the first infusion in the previous treatment course irrespective of progression in disease activity. After each treatment course, the participants attended their next trial visit 8 weeks after the first infusion of that course, followed by trial visits every 4 weeks up to Week 24, and subsequent visits every 8 weeks until the next treatment course. A maximum of 9 treatment courses were allowed.
Nervous system disorders Memory impairment	2.2% 2/92
Nervous system disorders Amnesia	1.1% 1/92
Nervous system disorders Aphasia	1.1% 1/92
Hepatobiliary disorders Cholecystitis	1.1% 1/92
Hepatobiliary disorders Cholelithiasis	1.1% 1/92
Nervous system disorders Disturbance in attention	1.1% 1/92
Injury, poisoning and procedural complications Fall	1.1% 1/92
Vascular disorders Hypertension	1.1% 1/92
Injury, poisoning and procedural complications Joint dislocation	1.1% 1/92
Cardiac disorders Myocardial infarction	1.1% 1/92
Musculoskeletal and connective tissue disorders Osteitis	1.1% 1/92
Gastrointestinal disorders Pancreatitis	1.1% 1/92
Infections and infestations Pneumonia	1.1% 1/92
Skin and subcutaneous tissue disorders Rash	1.1% 1/92
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	1.1% 1/92
Eye disorders Visual impairment	1.1% 1/92

Other adverse events

Other adverse events
Measure	Ofatumumab 700 mg IV Infusion n=92 participants at risk Ofatumumab was administered in the dose of 700 milligrams (mg) as two intravenous (IV) infusions separated by 2 weeks for the first treatment course. The remaining treatment courses were given at individualized time intervals when a clinical response had been achieved following the previous treatment course and a subsequent worsening in disease activity had been observed. For the remaining treatment courses, the interval between the treatment courses was at least 16 weeks from the first infusion in the previous treatment course irrespective of progression in disease activity. After each treatment course, the participants attended their next trial visit 8 weeks after the first infusion of that course, followed by trial visits every 4 weeks up to Week 24, and subsequent visits every 8 weeks until the next treatment course. A maximum of 9 treatment courses were allowed.
Infections and infestations Upper respiratory tract infection	15.2% 14/92
Infections and infestations Rhinitis	5.4% 5/92
Infections and infestations Urinary tract infection	5.4% 5/92
Infections and infestations Bronchitis	4.3% 4/92
Infections and infestations Nasopharyngitis	4.3% 4/92
Infections and infestations Oral herpes	4.3% 4/92
Infections and infestations Influenza	3.3% 3/92
Infections and infestations Pharyngitis	3.3% 3/92
Infections and infestations Respiratory tract infection	3.3% 3/92
Infections and infestations Sinusitis	3.3% 3/92
Infections and infestations Abscess	2.2% 2/92
Infections and infestations Cystitis	2.2% 2/92
Infections and infestations Lower respiratory tract infection	2.2% 2/92
Infections and infestations Enterobiasis	1.1% 1/92
Infections and infestations Eye infection	1.1% 1/92
Infections and infestations Furuncle	1.1% 1/92
Infections and infestations Gastroenteritis viral	1.1% 1/92
Infections and infestations Laryngitis	1.1% 1/92
Infections and infestations Lobar pneumonia	1.1% 1/92
Infections and infestations Pneumonia	1.1% 1/92
Infections and infestations Rash pustular	1.1% 1/92
Infections and infestations Skin infection	1.1% 1/92
Infections and infestations Tonsillitis	1.1% 1/92
Infections and infestations Tracheitis	1.1% 1/92
Skin and subcutaneous tissue disorders Rash	21.7% 20/92
Skin and subcutaneous tissue disorders Urticaria	5.4% 5/92
Skin and subcutaneous tissue disorders Pruritus	3.3% 3/92
Skin and subcutaneous tissue disorders Alopecia	2.2% 2/92
Skin and subcutaneous tissue disorders Rash generalized	2.2% 2/92
Skin and subcutaneous tissue disorders Dry skin	1.1% 1/92
Skin and subcutaneous tissue disorders Erythema	1.1% 1/92
Skin and subcutaneous tissue disorders Psoriasis	1.1% 1/92
Skin and subcutaneous tissue disorders Rash erythematous	1.1% 1/92
Skin and subcutaneous tissue disorders Rash maculo-papular	1.1% 1/92
Respiratory, thoracic and mediastinal disorders Cough	10.9% 10/92
Respiratory, thoracic and mediastinal disorders Throat irritation	9.8% 9/92
Respiratory, thoracic and mediastinal disorders Sneezing	6.5% 6/92
Respiratory, thoracic and mediastinal disorders Dyspnea	5.4% 5/92
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.3% 3/92
Respiratory, thoracic and mediastinal disorders Dry throat	2.2% 2/92
Respiratory, thoracic and mediastinal disorders Throat tightness	2.2% 2/92
Respiratory, thoracic and mediastinal disorders Bronchospasm	1.1% 1/92
Respiratory, thoracic and mediastinal disorders Dysphonia	1.1% 1/92
Respiratory, thoracic and mediastinal disorders Nasal congestion	1.1% 1/92
Respiratory, thoracic and mediastinal disorders Nasal dryness	1.1% 1/92
Respiratory, thoracic and mediastinal disorders Pharyngeal edema	1.1% 1/92
Respiratory, thoracic and mediastinal disorders Postnasal drip	1.1% 1/92
Respiratory, thoracic and mediastinal disorders Rhinorrhea	1.1% 1/92
Musculoskeletal and connective tissue disorders Back pain	2.2% 2/92
Musculoskeletal and connective tissue disorders Bursitis	2.2% 2/92
Musculoskeletal and connective tissue disorders Rheumatoid arthritis	2.2% 2/92
Musculoskeletal and connective tissue disorders Arthralgia	1.1% 1/92
Musculoskeletal and connective tissue disorders Flank pain	1.1% 1/92
Musculoskeletal and connective tissue disorders Joint range of motion decreased	1.1% 1/92
Musculoskeletal and connective tissue disorders Limb discomfort	1.1% 1/92
Musculoskeletal and connective tissue disorders Muscle spasms	1.1% 1/92
Musculoskeletal and connective tissue disorders Neck pain	1.1% 1/92
Musculoskeletal and connective tissue disorders Osteitis	1.1% 1/92
Musculoskeletal and connective tissue disorders Osteoarthritis	1.1% 1/92
Musculoskeletal and connective tissue disorders Pain in extremity	1.1% 1/92
Musculoskeletal and connective tissue disorders Sensation of heaviness	1.1% 1/92
Musculoskeletal and connective tissue disorders Spondylolisthesis	1.1% 1/92
Musculoskeletal and connective tissue disorders Synovial cyst	1.1% 1/92
Musculoskeletal and connective tissue disorders Tendon disorder	1.1% 1/92
Nervous system disorders Headache	9.8% 9/92
Nervous system disorders Aphasia	3.3% 3/92
Nervous system disorders Memory impairment	3.3% 3/92
Nervous system disorders Disturbance in attention	2.2% 2/92
Nervous system disorders Hypoaesthesia	2.2% 2/92
Nervous system disorders Sciatica	2.2% 2/92
Nervous system disorders Amnesia	1.1% 1/92
Nervous system disorders Dysgeusia	1.1% 1/92
Nervous system disorders Meralgia paraesthetica	1.1% 1/92
Nervous system disorders Neuralgia	1.1% 1/92
Nervous system disorders Paraesthesia	1.1% 1/92
Gastrointestinal disorders Nausea	3.3% 3/92
Gastrointestinal disorders Diarrhea	2.2% 2/92
Gastrointestinal disorders Dry mouth	2.2% 2/92
Gastrointestinal disorders Dysphagia	2.2% 2/92
Gastrointestinal disorders Periodontitis	2.2% 2/92
Gastrointestinal disorders Abdominal distension	1.1% 1/92
Gastrointestinal disorders Dental caries	1.1% 1/92
Gastrointestinal disorders Duodenal ulcer	1.1% 1/92
Gastrointestinal disorders Mouth ulceration	1.1% 1/92
Gastrointestinal disorders Pancreatitis	1.1% 1/92
Gastrointestinal disorders Vomiting	1.1% 1/92
Investigations Hepatic enzyme Increased	3.3% 3/92
Investigations Alanine aminotransferase increased	2.2% 2/92
Investigations Aspartate aminotransferase increased	2.2% 2/92
Investigations Blood creatinine increased	2.2% 2/92
Investigations Blood alkaline phosphatase increased	1.1% 1/92
Investigations Blood immunoglobulin G decreased	1.1% 1/92
Investigations Blood pressure increased	1.1% 1/92
Investigations Blood urea increased	1.1% 1/92
Investigations Blood uric acid increased	1.1% 1/92
Investigations Cardiac murmur	1.1% 1/92
Investigations Heart rate abnormal	1.1% 1/92
Investigations John Cunningham virus test positive	1.1% 1/92
Investigations Neutrophil count decreased	1.1% 1/92
Investigations Transaminases increased	1.1% 1/92
Blood and lymphatic system disorders Neutropenia	5.4% 5/92
Blood and lymphatic system disorders Leukopenia	4.3% 4/92
Blood and lymphatic system disorders Anemia	3.3% 3/92
Blood and lymphatic system disorders Lymphopenia	2.2% 2/92
Blood and lymphatic system disorders Lymphadenopathy	1.1% 1/92
Eye disorders Conjunctivitis	3.3% 3/92
Eye disorders Dry eye	3.3% 3/92
Eye disorders Visual impairment	2.2% 2/92
Eye disorders Conjunctival irritation	1.1% 1/92
Eye disorders Eye swelling	1.1% 1/92
Eye disorders Eyelid edema	1.1% 1/92
Eye disorders Lacrimation increased	1.1% 1/92
Eye disorders Photopsia	1.1% 1/92
Eye disorders Vision blurred	1.1% 1/92
Eye disorders Visual acuity reduced	1.1% 1/92
Eye disorders Vitreous floaters	1.1% 1/92
Vascular disorders Hypertension	4.3% 4/92
Vascular disorders Flushing	3.3% 3/92
Vascular disorders Varicophlebitis	1.1% 1/92
Vascular disorders Varicose vein	1.1% 1/92
Injury, poisoning and procedural complications Fall	1.1% 1/92
Injury, poisoning and procedural complications Fibula fracture	1.1% 1/92
Injury, poisoning and procedural complications Joint dislocation	1.1% 1/92
Injury, poisoning and procedural complications Limb crushing injury	1.1% 1/92
Injury, poisoning and procedural complications Patella fracture	1.1% 1/92
Injury, poisoning and procedural complications Tendon rupture	1.1% 1/92
Injury, poisoning and procedural complications Upper limb fracture	1.1% 1/92
General disorders Fatigue	4.3% 4/92
General disorders Edema peripheral	2.2% 2/92
General disorders Chest discomfort	1.1% 1/92
General disorders Influenza like illness	1.1% 1/92
General disorders Thirst	1.1% 1/92
Ear and labyrinth disorders Vertigo	3.3% 3/92
Ear and labyrinth disorders Ear pruritus	1.1% 1/92
Ear and labyrinth disorders Tinnitus	1.1% 1/92
Cardiac disorders Atrial fibrillation	1.1% 1/92
Cardiac disorders Myocardial infarction	1.1% 1/92
Cardiac disorders Tachycardia	1.1% 1/92
Immune system disorders Oral allergy syndrome	2.2% 2/92
Immune system disorders Allergy to vaccine	1.1% 1/92
Metabolism and nutrition disorders Fluid retention	1.1% 1/92
Metabolism and nutrition disorders Gout	1.1% 1/92
Metabolism and nutrition disorders Hyperuricemia	1.1% 1/92
Metabolism and nutrition disorders Increased appetite	1.1% 1/92
Psychiatric disorders Anxiety	1.1% 1/92
Psychiatric disorders Depression	1.1% 1/92
Psychiatric disorders Insomnia	1.1% 1/92
Psychiatric disorders Stress	1.1% 1/92
Renal and urinary disorders Leukocyturia	1.1% 1/92
Renal and urinary disorders Nephrolithiasis	1.1% 1/92
Renal and urinary disorders Nocturia	1.1% 1/92
Renal and urinary disorders Proteinuria	1.1% 1/92
Renal and urinary disorders Renal impairment	1.1% 1/92
Congenital, familial and genetic disorders Demoid cyst	1.1% 1/92
Hepatobiliary disorders Cholecystitis	1.1% 1/92
Hepatobiliary disorders Cholelithiasis	1.1% 1/92
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seborrhoeic keratosis	1.1% 1/92
Reproductive system and breast disorders Breast pain	1.1% 1/92

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER