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Ofatumumab Subcutaneous Administration in Subjects With Relapsing-Remitting Multiple Sclerosis (MIRROR)

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ClinicalTrials.gov Identifier: NCT01457924
Recruitment Status : Completed
First Posted : October 24, 2011
Results First Posted : March 1, 2018
Last Update Posted : June 5, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Multiple Sclerosis
Interventions Drug: Ofatumumab 3mg
Drug: Ofatumumab 30mg
Drug: Ofatumumab 60mg
Drug: Placebo
Enrollment 232
Recruitment Details A participant (par.) completed the study if he/she completed all assessments up to and including the 24 Week Follow-up Phase (FUP) (Week 48) without prematurely discontinuing.
Pre-assignment Details A total of 324 par. with Relapsing-Remitting Multiple Sclerosis (RRMS) were screened and 232 par. were randomized to 24 Week Treatment Phase (Weeks 0-12 were placebo controlled) of the study. A total of 231 par. received at least one dose of double-blind Investigational Product (IP) and were included in the Safety Population.
Arm/Group Title Placebo/Ofatumumab 3 mg Ofatumumab 3 mg q12w Ofatumumab 30 mg q12w Ofatumumab 60 mg q12w Ofatumumab 60mg q4w
Hide Arm/Group Description Par. received ofatumumab matching placebo subcutaneous (SC) injection every 4 weeks (q4w) from Week 0 to Week 20, except on Week 12 participants received 3 milligrams (mg) ofatumumab SC injection. Participants also received pre-medication of acetaminophen 1 gram (g) and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product. Par. received ofatumumab 3 mg SC injection every 12th week (q12w) on Week 1 and Week 12. Participants received matching placebo on Weeks 0, 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product. Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 30 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product. Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product. Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q4w from Week 1 to Week 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Period Title: Treatment Phase (Weeks 0-24)
Started 67 34 32 34 64
Completed to Week 12 65 31 30 33 60
Completed 64 29 30 33 58
Not Completed 3 5 2 1 6
Reason Not Completed
Adverse Event             0             4             1             0             2
Physician Decision             0             0             0             0             1
Lack of Efficacy             1             0             0             0             0
Protocol Violation             1             0             1             0             0
Withdrawal by Subject             0             0             0             1             1
Other-Protocol defined stopping criteria             1             1             0             0             2
Period Title: FUP (Weeks 24-48)
Started [1] 66 31 32 33 59
Completed 63 30 30 32 57
Not Completed 3 1 2 1 2
Reason Not Completed
Adverse Event             0             0             1             0             0
Physician Decision             1             0             1             0             0
Lost to Follow-up             0             0             0             1             0
Withdrawal by Subject             2             1             0             0             2
[1]
A total of 221 par. entered the FUP, including 7 of the 17 par. who were withdrawn before Week 24.
Period Title: Individualized FUP (Weeks 48+)
Started [1] 16 18 16 20 42
Completed 11 14 12 15 36
Not Completed 5 4 4 5 6
Reason Not Completed
Lost to Follow-up             1             0             1             0             0
Other-Protocol defined stopping criteria             3             4             2             3             5
Withdrawal by Subject             1             0             1             2             1
[1]
Par. whose CD19+ B lymphocyte counts had not recovered to lower limit of normal entered IFU phase.
Arm/Group Title Placebo/Ofatumumab 3 mg Ofatumumab 3 mg q12w Ofatumumab 30 mg q12w Ofatumumab 60 mg q12w Ofatumumab 60mg q4w Total
Hide Arm/Group Description Par. received ofatumumab matching placebo SC injection q4w from Week 0 to Week 20, except on Week 12 participants received 3 mg ofatumumab SC injection. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product. Par. received ofatumumab 3 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 0, 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product. Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 30 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product. Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product. Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q4w from Week 1 to Week 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product. Total of all reporting groups
Overall Number of Baseline Participants 67 34 32 34 64 231
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 67 participants 34 participants 32 participants 34 participants 64 participants 231 participants
37.7  (9.38) 38.1  (8.29) 37.2  (10.04) 37.3  (9.67) 36.2  (9.57) 37.2  (9.36)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 67 participants 34 participants 32 participants 34 participants 64 participants 231 participants
Female
46
  68.7%
22
  64.7%
24
  75.0%
22
  64.7%
41
  64.1%
155
  67.1%
Male
21
  31.3%
12
  35.3%
8
  25.0%
12
  35.3%
23
  35.9%
76
  32.9%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
 Number Analyzed 67 participants 34 participants 32 participants 34 participants 64 participants 231 participants
African American/African Heritage 1 0 0 0 1 2
Asian - East Asian Heritage 0 0 1 0 0 1
White - White/Caucasian/European Heritage 65 34 31 34 61 225
Mixed Race 1 0 0 0 2 3
1.Primary Outcome
Title Cumulative Number of New Gadolinium-enhancing (GdE) T1 Lesions at Week 12
Hide Description The cumulative number of new GdE T1 lesion at Week 12 were analyzed from screening based on magnetic resonance imaging (MRI) brain scans at Weeks 4, 8, and 12. The outcome measure was analyzed using an Emax model adjusting for the presence/absence of GdE lesions on the Screening MRI and assuming the number of new lesions followed a negative binomial distribution. Dose was fitted as a continuous variable. The number of scans contributing to the cumulative number of lesions was fitted as an offset. Estimates of the rate of cumulative number of new GdE lesions per scan at Week 12 were determined from the model. The all evaluable scans (AES) dataset was used which included all evaluable on-treatment MRI scans for each participant analysed.
Time Frame Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population comprised of all randomized par. who received at least one dose of IP and who had at least one post screen MRI assessment. Only those par. available at the specified time points were analyzed. Please see footnote of statistical analysis 1 for discrepancy in analysis population Week 24 and 48.
Arm/Group Title Placebo/Ofatumumab 3 mg Ofatumumab 3 mg q12w Ofatumumab 30 mg q12w Ofatumumab 60 mg q12w Ofatumumab 60mg q4w
Hide Arm/Group Description:
Par. received ofatumumab matching placebo SC injection q4w from Week 0 to Week 20, except on Week 12 participants received 3 mg ofatumumab SC injection. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 0, 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 30 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q4w from Week 1 to Week 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Overall Number of Participants Analyzed 67 33 30 33 63
Mean (Standard Deviation)
Unit of Measure: Cumulative number of lesions
4.2  (7.57) 1.7  (3.29) 2.2  (3.41) 2.2  (3.70) 1.2  (2.83)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 3 mg q12w
Comments Note: There is a discrepancy in the number of par. in ITT populations at Wk 24 and Wk 48: 228 and 229 respectively. This resulted from a data issue: one par was incorrectly excluded from ITT pop. at Wk 24, but correctly included in Wk 48. This error affects all source tables, analyses relating to ITT and per protocol populations, primary endpoint and secondary MRI endpoints reported at Wk 24. This discrepancy affects all statistical analyses, but not summary statistics.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Non-Linear Emax Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.35
Confidence Interval (2-Sided) 95%
0.221 to 0.548
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 30 mg q12w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Non-Linear Emax Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.35
Confidence Interval (2-Sided) 95%
0.221 to 0.548
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 60 mg q12w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Non-Linear Emax Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.35
Confidence Interval (2-Sided) 95%
0.221 to 0.548
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 60mg q4w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Non-Linear Emax Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.35
Confidence Interval (2-Sided) 95%
0.221 to 0.548
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Cumulative Number of New GdE T1 Lesions at Week 24
Hide Description The cumulative number of new GdE T1 lesion at Week 24 were analyzed from screen based on MRI brain scans at Weeks 4, 8, 12, 16, 20 and 24. Anticipating an underlying negative binomial distribution with a log-link function, adjusted for treatment and presence/absence of GdE lesions on the Screening MRI. Treatment group was fitted as a categorical variable. The number of scans contributing to the cumulative number of lesions was fitted as an offset. Estimates of the rate of cumulative number of new GdE T1 lesions per scan at Week 24 were determined from the model. The AES dataset was used which included all evaluable on-treatment MRI scans for each participant analyzed.
Time Frame Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title Placebo/Ofatumumab 3 mg Ofatumumab 3 mg q12w Ofatumumab 30 mg q12w Ofatumumab 60 mg q12w Ofatumumab 60mg q4w
Hide Arm/Group Description:
Par. received ofatumumab matching placebo SC injection q4w from Week 0 to Week 20, except on Week 12 participants received 3 mg ofatumumab SC injection. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 0, 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 30 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q4w from Week 1 to Week 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Overall Number of Participants Analyzed 67 33 30 33 63
Mean (Standard Deviation)
Unit of Measure: Cumulative number of lesions
5.6  (9.34) 2.2  (3.80) 2.5  (3.88) 2.2  (3.83) 1.4  (3.04)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 3 mg q12w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Generalized Linear Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.38
Confidence Interval (2-Sided) 95%
0.20 to 0.72
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 30 mg q12w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Generalized Linear Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.38
Confidence Interval (2-Sided) 95%
0.20 to 0.72
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 60 mg q12w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments [Not Specified]
Method Generalized Linear Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.35
Confidence Interval (2-Sided) 95%
0.19 to 0.65
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 60mg q4w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Generalized Linear Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.23
Confidence Interval (2-Sided) 95%
0.13 to 0.39
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Brain Volume at Week 24 and Week 48
Hide Description Brain volume is a measure of brain size determined by a MRI scan. Baseline is defined as the par. last available assessment prior to initiation of the IP (i.e. Screening). Change from Baseline was calculated by subtracting the Baseline value from the post-Baseline value.
Time Frame Baseline (Week 0), Week 24 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those par. available at the specified time points were analyzed.
Arm/Group Title Placebo/Ofatumumab 3 mg Ofatumumab 3 mg q12w Ofatumumab 30 mg q12w Ofatumumab 60 mg q12w Ofatumumab 60mg q4w
Hide Arm/Group Description:
Par. received ofatumumab matching placebo SC injection q4w from Week 0 to Week 20, except on Week 12 participants received 3 mg ofatumumab SC injection. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 0, 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 30 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q4w from Week 1 to Week 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Overall Number of Participants Analyzed 28 12 16 12 22
Mean (Standard Deviation)
Unit of Measure: Cubic centimeters
Week 24 Number Analyzed 25 participants 12 participants 16 participants 12 participants 22 participants
-13.5  (26.96) -7.2  (22.26) -8.4  (26.62) -13.3  (34.02) -1.4  (56.42)
Week 48 Number Analyzed 28 participants 12 participants 16 participants 11 participants 19 participants
-22.0  (38.22) -12.9  (14.55) -5.0  (28.84) -7.3  (29.16) -11.8  (55.30)
4.Secondary Outcome
Title Cumulative Number of Persistent GdE Brain Lesions on T1-weighted MRI at Week 12
Hide Description The cumulative number of persistent GdE T1 lesions at Week 12 were analyzed from screen based on MRI scans at Weeks 4, 8, and 12. The AES dataset was used which included all evaluable on-treatment MRI scans for each par. analyzed.
Time Frame Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those par. available at the specified time points were analyzed.
Arm/Group Title Placebo/Ofatumumab 3 mg Ofatumumab 3 mg q12w Ofatumumab 30 mg q12w Ofatumumab 60 mg q12w Ofatumumab 60mg q4w
Hide Arm/Group Description:
Par. received ofatumumab matching placebo SC injection q4w from Week 0 to Week 20, except on Week 12 participants received 3 mg ofatumumab SC injection. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 0, 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 30 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q4w from Week 1 to Week 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Overall Number of Participants Analyzed 67 34 30 33 63
Mean (Standard Deviation)
Unit of Measure: Number of lesions per scan
3.2  (7.41) 1.2  (1.94) 2.3  (3.94) 1.8  (3.31) 1.8  (4.81)
5.Secondary Outcome
Title Cumulative Number of All (New Plus Persistent) GdE Brain Lesions on T1-weighted MRI at Week 12
Hide Description The cumulative number of all (new plus persistent) GdE T1 lesion at Week 12 were analyzed from screen based on MRI brain scans at Weeks 4, 8 and 12. Anticipating an underlying negative binomial distribution with a log-link function, adjusted for treatment and presence/absence of GdE lesions on the Screening MRI. Treatment group was fitted as a categorical variable. The number of scans contributing to the cumulative number of lesions was fitted as an offset. Estimates of the rate of cumulative number of all (new plus persistent) GdE T1 lesions per scan at Week 12 were determined from the model. The AES dataset was used which included all evaluable on-treatment MRI scans for each par. analyzed.
Time Frame Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those par. available at the specified time points were analyzed.
Arm/Group Title Placebo/Ofatumumab 3 mg Ofatumumab 3 mg q12w Ofatumumab 30 mg q12w Ofatumumab 60 mg q12w Ofatumumab 60mg q4w
Hide Arm/Group Description:
Par. received ofatumumab matching placebo SC injection q4w from Week 0 to Week 20, except on Week 12 participants received 3 mg ofatumumab SC injection. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 0, 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 30 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q4w from Week 1 to Week 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Overall Number of Participants Analyzed 67 33 30 33 63
Mean (Standard Deviation)
Unit of Measure: Cumulative number of lesions
7.4  (13.90) 2.9  (4.62) 4.5  (7.09) 4.0  (6.70) 3.1  (6.82)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 3 mg q12w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Generalized Linear Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.31
Confidence Interval (2-Sided) 95%
0.16 to 0.60
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 30 mg q12w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.075
Comments [Not Specified]
Method Generalized Linear Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.56
Confidence Interval (2-Sided) 95%
0.29 to 1.06
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 60 mg q12w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.035
Comments [Not Specified]
Method Generalized Linear Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.51
Confidence Interval (2-Sided) 95%
0.27 to 0.95
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 60mg q4w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Generalized Linear Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.32
Confidence Interval (2-Sided) 95%
0.19 to 0.55
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Total Volume of New GdE Brain Lesions on T1-weighted MRI at Week 12
Hide Description Lesion volume is a measure of lesion size determined by a MRI brain scan. The cumulative volume of new GdE T1 lesions at Week 12 were analyzed from screen based on MRI brain scans at Weeks 4, 8 and 12. Anticipating an underlying negative binomial distribution with a log-link function, adjusted for treatment and presence/absence of GdE lesions on the Screening MRI. Treatment group was fitted as a categorical variable. The number of scans contributing to the cumulative volume of lesions was fitted as an offset. Estimates of the rate of cumulative volume of new GdE T1 lesions per scan at Week 12 were determined from the model. The AES dataset was used which included all evaluable on-treatment MRI scans for each par. analyzed.
Time Frame Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those par. available at the specified time points were analyzed.
Arm/Group Title Placebo/Ofatumumab 3 mg Ofatumumab 3 mg q12w Ofatumumab 30 mg q12w Ofatumumab 60 mg q12w Ofatumumab 60mg q4w
Hide Arm/Group Description:
Par. received ofatumumab matching placebo SC injection q4w from Week 0 to Week 20, except on Week 12 participants received 3 mg ofatumumab SC injection. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 0, 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 30 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q4w from Week 1 to Week 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Overall Number of Participants Analyzed 67 34 30 33 63
Mean (Standard Deviation)
Unit of Measure: Cubic millimeter (mm^3)
607.5  (1090.89) 226.5  (449.37) 452.9  (682.33) 248.6  (457.62) 146.6  (304.89)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 3 mg q12w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.026
Comments [Not Specified]
Method Generalized Linear Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.22
Confidence Interval (2-Sided) 95%
0.06 to 0.84
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 30 mg q12w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.296
Comments [Not Specified]
Method Generalized Linear Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.49
Confidence Interval (2-Sided) 95%
0.13 to 1.86
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 60 mg q12w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.285
Comments [Not Specified]
Method Generalized Linear Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
0.14 to 1.78
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 60mg q4w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.009
Comments [Not Specified]
Method Non-Linear Emax Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.25
Confidence Interval (2-Sided) 95%
0.09 to 0.71
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Total Volume of All (New and Persistent) GdE Brain Lesions on T1-weighted MRI at Week 12
Hide Description Lesion volume is a measure of lesion size determined by a MRI brain scan. The cumulative volume of all (new and persistent) GdE T1 lesions at Week 12 were analyzed from screen based on MRI brain scans at Weeks 4, 8 and 12. The endpoint was analyzed using a generalized linear model assuming an underlying negative binomial distribution with a log-link function, adjusted for treatment and presence/absence of GdE lesions on the Screening MRI. Treatment group was fitted as a categorical variable. The number of scans contributing to the cumulative volume of lesions was fitted as an offset. Estimates of the rate of cumulative volume of all (new and persistent) GdE T1 lesions per scan at Week 12 were determined from the model. The AES dataset was used which included all evaluable on-treatment MRI scans for each par. analyzed.
Time Frame Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those par. available at the specified time points were analyzed.
Arm/Group Title Placebo/Ofatumumab 3 mg Ofatumumab 3 mg q12w Ofatumumab 30 mg q12w Ofatumumab 60 mg q12w Ofatumumab 60mg q4w
Hide Arm/Group Description:
Par. received ofatumumab matching placebo SC injection q4w from Week 0 to Week 20, except on Week 12 participants received 3 mg ofatumumab SC injection. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 0, 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 30 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q4w from Week 1 to Week 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Overall Number of Participants Analyzed 67 33 30 33 63
Mean (Standard Deviation)
Unit of Measure: mm^3
1039.6  (1809.97) 386.2  (628.41) 886.2  (1637.47) 426.5  (679.44) 344.4  (735.57)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 3 mg q12w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method Generalized Linear Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.18
Confidence Interval (2-Sided) 95%
0.05 to 0.58
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 30 mg q12w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.248
Comments [Not Specified]
Method Generalized Linear Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.50
Confidence Interval (2-Sided) 95%
0.15 to 1.63
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 60 mg q12w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.181
Comments [Not Specified]
Method Generalized Linear Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.46
Confidence Interval (2-Sided) 95%
0.15 to 1.43
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 60mg q4w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Generalized Linear Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.24
Confidence Interval (2-Sided) 95%
0.10 to 0.62
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Cumulative Number of New and Newly Enlarging GdE T2 Lesions at Week 12
Hide Description The cumulative number of new and newly enlarging GdE T2 lesions (NET2L) at Week 12 were analyzed from screen based on MRI brain scans at Weeks 4, 8 and 12. The endpoint was analyzed using a generalized linear model assuming an underlying negative binomial distribution with a log-link function, adjusted for treatment and presence/absence of GdE lesions on the Screening MRI. Treatment group was fitted as a categorical variable. The number of scans contributing to the cumulative number of lesions was fitted as an offset. Estimates of the rate of cumulative number of NET2L per scan at Week 12 were determined from the model. The AES dataset was used which included all evaluable on-treatment MRI scans for each par. analyzed.
Time Frame Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those par. available at the specified time points were analyzed.
Arm/Group Title Placebo/Ofatumumab 3 mg Ofatumumab 3 mg q12w Ofatumumab 30 mg q12w Ofatumumab 60 mg q12w Ofatumumab 60mg q4w
Hide Arm/Group Description:
Par. received ofatumumab matching placebo SC injection q4w from Week 0 to Week 20, except on Week 12 participants received 3 mg ofatumumab SC injection. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 0, 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 30 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q4w from Week 1 to Week 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Overall Number of Participants Analyzed 67 33 30 33 63
Mean (Standard Deviation)
Unit of Measure: Cumulative number of lesions
3.7  (6.72) 1.2  (2.38) 1.6  (2.79) 1.7  (2.67) 0.8  (1.55)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 3 mg q12w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Generalized Linear Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.29
Confidence Interval (2-Sided) 95%
0.15 to 0.58
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 30 mg q12w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Generalized Linear Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.34
Confidence Interval (2-Sided) 95%
0.17 to 0.68
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 60 mg q12w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments [Not Specified]
Method Generalized Linear Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.40
Confidence Interval (2-Sided) 95%
0.21 to 0.77
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Placebo/Ofatumumab 3 mg, Ofatumumab 60mg q4w
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Generalized Linear Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
0.11 to 0.35
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Total Volume of New and/or Newly Enlarging T2 Lesions at Week 12
Hide Description Lesion volume is a measure of lesion size determined by a MRI brain scan. T2 lesions, are indicative of brain myelin content.The cumulative volume of new and/or newly enlarging T2 lesions at Week 12 were analyzed from screen based on MRI brain scans at Weeks 4, 8, and 12. The AES dataset was used which included all evaluable on-treatment MRI scans for each par.
Time Frame Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those par. available at the specified time points were analyzed.
Arm/Group Title Placebo/Ofatumumab 3 mg Ofatumumab 3 mg q12w Ofatumumab 30 mg q12w Ofatumumab 60 mg q12w Ofatumumab 60mg q4w
Hide Arm/Group Description:
Par. received ofatumumab matching placebo SC injection q4w from Week 0 to Week 20, except on Week 12 participants received 3 mg ofatumumab SC injection. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 0, 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 30 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q4w from Week 1 to Week 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Overall Number of Participants Analyzed 67 34 30 33 63
Mean (Standard Deviation)
Unit of Measure: mm^3
1204.5  (3426.79) 279.9  (695.75) 611.3  (1042.06) 293.8  (576.35) 167.9  (450.65)
10.Secondary Outcome
Title Cumulative Number of New T1 Hypointense Lesions at Week 24 and Week 48
Hide Description The cumulative number of new T1 hypointense lesions at week 24 were analyzed from screen based on MRI brain scans at Weeks 4, 8, 12, 16, 20 and 24. The AES dataset was used which included all evaluable on-treatment MRI scans for each par.
Time Frame Week 24 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those par. available at the specified time points were analyzed.
Arm/Group Title Placebo/Ofatumumab 3 mg Ofatumumab 3 mg q12w Ofatumumab 30 mg q12w Ofatumumab 60 mg q12w Ofatumumab 60mg q4w
Hide Arm/Group Description:
Par. received ofatumumab matching placebo SC injection q4w from Week 0 to Week 20, except on Week 12 participants received 3 mg ofatumumab SC injection. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 0, 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 30 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q4w from Week 1 to Week 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Overall Number of Participants Analyzed 67 34 32 33 63
Mean (Standard Deviation)
Unit of Measure: Number of lesions
Week 24 Number Analyzed 67 participants 34 participants 30 participants 33 participants 63 participants
0.4  (0.96) 0.4  (1.26) 0.5  (1.01) 0.5  (1.12) 0.3  (0.78)
Week 48 Number Analyzed 67 participants 34 participants 32 participants 33 participants 63 participants
0.6  (1.27) 0.5  (1.26) 0.5  (0.98) 0.6  (1.25) 0.3  (0.96)
11.Secondary Outcome
Title Cumulative Volume of New T1 Hypointense Lesions at Week 24 and Week 48
Hide Description Lesion volume is a measure of lesion size determined by a MRI brain scan. Baseline is defined as the participant’s last available assessment prior to initiation of IP. Change from Baseline was calculated by subtracting the Baseline value from the post-Baseline value. The AES dataset was used which included all evaluable on-treatment MRI scans for each par.
Time Frame Baseline, Week 24 and Week 48
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those par. available at the specified time points were analyzed.
Arm/Group Title Placebo/Ofatumumab 3 mg Ofatumumab 3 mg q12w Ofatumumab 30 mg q12w Ofatumumab 60 mg q12w Ofatumumab 60mg q4w
Hide Arm/Group Description:
Par. received ofatumumab matching placebo SC injection q4w from Week 0 to Week 20, except on Week 12 participants received 3 mg ofatumumab SC injection. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 0, 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 30 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q4w from Week 1 to Week 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
Overall Number of Participants Analyzed 67 34 32 33 63
Mean (Standard Deviation)
Unit of Measure: mm^3
Week 24 Number Analyzed 67 participants 34 participants 30 participants 33 participants 63 participants
86.9  (240.40) 43.1  (131.96) 67.4  (147.00) 65.0  (139.14) 42.9  (140.93)
Week 48 Number Analyzed 67 participants 34 participants 32 participants 33 participants 63 participants
113.6  (270.89) 54.2  (137.74) 63.2  (143.14) 116.3  (370.35) 53.2  (173.62)
Time Frame On treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of administration of the study drug until the follow-up contact (up to Week 24).
Adverse Event Reporting Description SAEs and non-serious AEs were reported for members of the safety population, comprised of all par. who were randomized to treatment, and received at least one dose of study medication.
 
Arm/Group Title Placebo/Ofatumumab 3 mg Ofatumumab 3 mg q12w Ofatumumab 30 mg q12w Ofatumumab 60 mg q12w Ofatumumab 60mg q4w
Hide Arm/Group Description Par. received ofatumumab matching placebo SC injection q4w from Week 0 to Week 20, except on Week 12 participants received 3 mg ofatumumab SC injection. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product. Par. received ofatumumab 3 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 0, 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product. Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 30 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product. Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q12w on Week 1 and Week 12. Participants received matching placebo on Weeks 4, 8, 16 and 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product. Par. received ofatumumab 3 mg conditioning dose SC injection or matching placebo on Week 0 and received ofatumumab 60 mg SC injection q4w from Week 1 to Week 20. Participants also received pre-medication of acetaminophen 1 g and antihistamine (cetirizine or equivalent) 10 mg prior to administration of each SC injection of investigational product.
All-Cause Mortality
Placebo/Ofatumumab 3 mg Ofatumumab 3 mg q12w Ofatumumab 30 mg q12w Ofatumumab 60 mg q12w Ofatumumab 60mg q4w
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/67 (0.00%)   0/34 (0.00%)   0/32 (0.00%)   0/34 (0.00%)   0/64 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo/Ofatumumab 3 mg Ofatumumab 3 mg q12w Ofatumumab 30 mg q12w Ofatumumab 60 mg q12w Ofatumumab 60mg q4w
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/67 (0.00%)   1/34 (2.94%)   0/32 (0.00%)   1/34 (2.94%)   4/64 (6.25%) 
Hepatobiliary disorders           
Cholelithiasis † 1  0/67 (0.00%)  0/34 (0.00%)  0/32 (0.00%)  0/34 (0.00%)  1/64 (1.56%) 
Immune system disorders           
Cytokine release syndrome † 1  0/67 (0.00%)  0/34 (0.00%)  0/32 (0.00%)  1/34 (2.94%)  0/64 (0.00%) 
Injury, poisoning and procedural complications           
Injection related reaction † 1  0/67 (0.00%)  0/34 (0.00%)  0/32 (0.00%)  0/34 (0.00%)  2/64 (3.13%) 
Metabolism and nutrition disorders           
Hypokalaemia † 1  0/67 (0.00%)  0/34 (0.00%)  0/32 (0.00%)  0/34 (0.00%)  1/64 (1.56%) 
Skin and subcutaneous tissue disorders           
Angioedema † 1  0/67 (0.00%)  1/34 (2.94%)  0/32 (0.00%)  0/34 (0.00%)  0/64 (0.00%) 
Urticaria † 1  0/67 (0.00%)  1/34 (2.94%)  0/32 (0.00%)  0/34 (0.00%)  0/64 (0.00%) 
1
Term from vocabulary, MedDRA 16.0
†
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo/Ofatumumab 3 mg Ofatumumab 3 mg q12w Ofatumumab 30 mg q12w Ofatumumab 60 mg q12w Ofatumumab 60mg q4w
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   41/67 (61.19%)   20/34 (58.82%)   23/32 (71.88%)   22/34 (64.71%)   47/64 (73.44%) 
Blood and lymphatic system disorders           
Anaemia † 1  1/67 (1.49%)  2/34 (5.88%)  0/32 (0.00%)  1/34 (2.94%)  1/64 (1.56%) 
Gastrointestinal disorders           
Nausea † 1  4/67 (5.97%)  0/34 (0.00%)  1/32 (3.13%)  1/34 (2.94%)  2/64 (3.13%) 
Diarrhoea † 1  4/67 (5.97%)  0/34 (0.00%)  0/32 (0.00%)  0/34 (0.00%)  0/64 (0.00%) 
General disorders           
Fatigue † 1  8/67 (11.94%)  0/34 (0.00%)  3/32 (9.38%)  2/34 (5.88%)  3/64 (4.69%) 
Pyrexia † 1  2/67 (2.99%)  2/34 (5.88%)  2/32 (6.25%)  1/34 (2.94%)  1/64 (1.56%) 
Injection site pain † 1  0/67 (0.00%)  2/34 (5.88%)  0/32 (0.00%)  0/34 (0.00%)  1/64 (1.56%) 
Infections and infestations           
Nasopharyngitis † 1  8/67 (11.94%)  1/34 (2.94%)  4/32 (12.50%)  7/34 (20.59%)  7/64 (10.94%) 
Urinary tract infection † 1  4/67 (5.97%)  3/34 (8.82%)  3/32 (9.38%)  2/34 (5.88%)  1/64 (1.56%) 
Respiratory tract infection † 1  2/67 (2.99%)  1/34 (2.94%)  0/32 (0.00%)  2/34 (5.88%)  0/64 (0.00%) 
Injury, poisoning and procedural complications           
Injection related reaction † 1  18/67 (26.87%)  16/34 (47.06%)  13/32 (40.63%)  17/34 (50.00%)  42/64 (65.63%) 
Fall † 1  0/67 (0.00%)  2/34 (5.88%)  1/32 (3.13%)  0/34 (0.00%)  2/64 (3.13%) 
Investigations           
Reticulocyte count decreased † 1  1/67 (1.49%)  0/34 (0.00%)  2/32 (6.25%)  1/34 (2.94%)  1/64 (1.56%) 
Blood immunoglobulin G decreased † 1  0/67 (0.00%)  2/34 (5.88%)  0/32 (0.00%)  0/34 (0.00%)  1/64 (1.56%) 
Weight decreased † 1  0/67 (0.00%)  0/34 (0.00%)  2/32 (6.25%)  0/34 (0.00%)  0/64 (0.00%) 
Musculoskeletal and connective tissue disorders           
Back pain † 1  6/67 (8.96%)  1/34 (2.94%)  2/32 (6.25%)  0/34 (0.00%)  1/64 (1.56%) 
Arthralgia † 1  2/67 (2.99%)  1/34 (2.94%)  2/32 (6.25%)  1/34 (2.94%)  0/64 (0.00%) 
Nervous system disorders           
Headache † 1  7/67 (10.45%)  2/34 (5.88%)  2/32 (6.25%)  2/34 (5.88%)  6/64 (9.38%) 
Dizziness † 1  0/67 (0.00%)  0/34 (0.00%)  1/32 (3.13%)  0/34 (0.00%)  4/64 (6.25%) 
Neuralgia † 1  0/67 (0.00%)  0/34 (0.00%)  2/32 (6.25%)  0/34 (0.00%)  0/64 (0.00%) 
Psychiatric disorders           
Anxiety † 1  2/67 (2.99%)  1/34 (2.94%)  2/32 (6.25%)  0/34 (0.00%)  0/64 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Cough † 1  2/67 (2.99%)  2/34 (5.88%)  1/32 (3.13%)  0/34 (0.00%)  1/64 (1.56%) 
Skin and subcutaneous tissue disorders           
Ecchymosis † 1  0/67 (0.00%)  2/34 (5.88%)  0/32 (0.00%)  0/34 (0.00%)  1/64 (1.56%) 
1
Term from vocabulary, MedDRA 16.0
†
Indicates events were collected by systematic assessment
The incorrect exclusion of one par. from ITT pop. at Wk 24 was not considered to impact overall interpretation of data: no updates were made to source tables/analyses. This par. had withdrawn early, having never received a dose of active study drug.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01457924     History of Changes
Other Study ID Numbers: 112831
First Submitted: October 20, 2011
First Posted: October 24, 2011
Results First Submitted: March 21, 2017
Results First Posted: March 1, 2018
Last Update Posted: June 5, 2018