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Efficacy and Safety of Ofatumumab Compared to Teriflunomide in Patients With Relapsing Multiple Sclerosis. (ASCLEPIOS II)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02792231
Recruitment Status : Completed
First Posted : June 7, 2016
Results First Posted : October 19, 2020
Last Update Posted : November 22, 2021
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Relapsing Multiple Scelrosis
Interventions Drug: Ofatumumab subcutaneous injection
Drug: Teriflunomide-matching placebo capsules
Drug: Teriflunomide capsule
Drug: Matching placebo of ofatumumab subcutaneous injections
Enrollment 955
Recruitment Details It was pre-specified in the protocol to combine the data from this study with study NCT02792218 (COMB157G2301) for some outcome measures. Please refer to NCT02792218 for Participant Flow information for participants from other study.
Pre-assignment Details A total of 1280 patients were screened, of whom 955 patients were randomized into the study.
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily) Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Period Title: Overall Study
Started 481 474
Completed 399 390
Not Completed 82 84
Reason Not Completed
Patient/guardian decision             32             42
Adverse Event             15             11
Physician Decision             14             12
Lack of Efficacy             7             9
Lost to Follow-up             9             5
Pregnancy             1             3
Non-compliance with study treatment             2             1
Protocol deviation             2             0
Technical problems             0             1
Arm/Group Title OMB 20 mg TER 14 mg Total
Hide Arm/Group Description Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily) Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter) Total of all reporting groups
Overall Number of Baseline Participants 481 474 955
Hide Baseline Analysis Population Description
It was pre-specified in the protocol to combine the data from this study with study NCT02792218 (COMB157G2301) for some outcome measures. Please refer to NCT02792218 for Baseline information for participants from other study.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 481 participants 474 participants 955 participants
38.0  (9.28) 38.2  (9.47) 38.1  (9.37)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 481 participants 474 participants 955 participants
Female
319
  66.3%
319
  67.3%
638
  66.8%
Male
162
  33.7%
155
  32.7%
317
  33.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Asian Number Analyzed 481 participants 474 participants 955 participants
21
   4.4%
19
   4.0%
40
   4.2%
Black or African American Number Analyzed 481 participants 474 participants 955 participants
13
   2.7%
18
   3.8%
31
   3.2%
White Number Analyzed 481 participants 474 participants 955 participants
418
  86.9%
417
  88.0%
835
  87.4%
Other Number Analyzed 481 participants 474 participants 955 participants
20
   4.2%
14
   3.0%
34
   3.6%
Unknown Number Analyzed 481 participants 474 participants 955 participants
9
   1.9%
6
   1.3%
15
   1.6%
Number of relapses in the past 12 months prior to screening   [1] 
Mean (Standard Deviation)
Unit of measure:  Number of relapses
Number Analyzed 481 participants 474 participants 955 participants
1.3  (0.74) 1.3  (0.73) 1.3  (0.74)
[1]
Measure Description: Reported numbers are from investigator records
Expanded Disability Status Scale (EDSS)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Score on a scale
Number Analyzed 481 participants 473 participants 954 participants
2.90  (1.343) 2.86  (1.373) 2.88  (1.358)
[1]
Measure Description: The EDSS uses an ordinal scale to assess neurologic impairment in MS based on a neurological examination. Scores in each of 7 functional systems (Visual, Brain Stem, Pyramidal, Cerebellar,Sensory, Bowel & Bladder, and Cerebral) and an ambulation score were combined to determine the EDSS steps, ranging from 0 (normal) to 10 (death due to MS).
[2]
Measure Analysis Population Description: Participants with data that met requirements for analysis were included
Number of gadolinium-enhancing T1 lesions   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  T1 lesions
Number Analyzed 469 participants 470 participants 939 participants
1.6  (4.07) 1.5  (4.07) 1.5  (4.07)
[1]
Measure Description: Magnetic Resonance Imaging (MRI) scans of the brain were were read by the central MRI reading center. The central reading center was blinded with no access to information on treatment assignments
[2]
Measure Analysis Population Description: Participants with data that met requirements for analysis were included
1.Primary Outcome
Title Annualized Relapse Rate (ARR)
Hide Description ARR was the number of confirmed relapses in a year, calculated as the total number of relapses for all participants in the treatment group divided by the total participant-years of time in study. A confirmed MS relapse was defined as one accompanied by a clinically-relevant change in the EDSS performed by the Independent EDSS rater, i.e. an increase of at least 0.5 points on the EDSS score, or an increase of 1 point on two functional scores or 2 points on one functional score (excluding changes involving bowel/bladder or cerebral functional system). Comparisons were made to the previous rating (the last EDSS rating that did not occur during a relapse).
Time Frame Baseline up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 469 470
Mean (95% Confidence Interval)
Unit of Measure: number of relapses in a year
0.10
(0.08 to 0.13)
0.25
(0.21 to 0.30)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OMB 20 mg, TER 14 mg
Comments Obtained from fitting a negative binomial regression model with log-link to the number of relapses, adjusted for treatment and region as factors, number of relapses in previous year, baseline EDSS, baseline number of Gd-enhancing lesions and the patient's age at baseline as covariates. The natural log of the time-in-study was used as offset to annualize the relapse rate.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method negative binomial regression model
Comments [Not Specified]
Method of Estimation Estimation Parameter rate ratio
Estimated Value 0.416
Confidence Interval (2-Sided) 95%
0.309 to 0.560
Estimation Comments [Not Specified]
2.Secondary Outcome
Title 3-month Confirmed Disability Worsening (3mCDW) Based on EDSS - Pooled Data
Hide Description A 3-month confirmed disability worsening (3mCDW) was defined as an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at least 3 months. For patients with a baseline EDSS of 0, the criterion for disability worsening was an increase in EDSS of ≥1.5, for patients with a baseline EDSS of 1 to 5 or ≥5.5, the criterion for disability worsening was an increase in EDSS of ≥1 or ≥0.5, respectively. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2301 to address this endpoint.
Time Frame Baseline, every 3 months up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set from combined studies
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 944 932
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 18 - from Kaplan Meier estimates
9.4
(7.6 to 11.5)
13.5
(11.4 to 16.0)
Month 24 - from Kaplan Meier estimates
10.9
(8.8 to 13.4)
15.0
(12.6 to 17.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OMB 20 mg, TER 14 mg
Comments Pooled data - this study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2301 to address this endpoint.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.003
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.657
Confidence Interval (2-Sided) 95%
0.500 to 0.863
Estimation Comments [Not Specified]
3.Secondary Outcome
Title 3-month Confirmed Disability Worsening (3mCDW) Based on EDSS - Study COMB157G2302
Hide Description A 3-month confirmed disability worsening (3mCDW) was defined as an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at least 3 months. For patients with a baseline EDSS of 0, the criterion for disability worsening was an increase in EDSS of ≥1.5, for patients with a baseline EDSS of 1 to 5 or ≥5.5, the criterion for disability worsening was an increase in EDSS of ≥1 or ≥0.5, respectively. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2301 to address this endpoint.
Time Frame Baseline, every 3 months up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 479 473
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 18 - from Kaplan Meier estimates
9.3
(6.9 to 12.5)
13.2
(10.3 to 16.7)
Month 24 - from Kaplan Meier estimates
10.5
(7.8 to 14.1)
14.6
(11.5 to 18.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OMB 20 mg, TER 14 mg
Comments This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2301 to address this endpoint.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.038
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.662
Confidence Interval (2-Sided) 95%
0.449 to 0.977
Estimation Comments [Not Specified]
4.Secondary Outcome
Title 6-month Confirmed Disability Worsening (6mCDW) Based on EDSS - Pooled Data
Hide Description A 6-month confirmed disability worsening (6mCDW) was defined as an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at least 6 months. For patients with a baseline EDSS of 0, the criterion for disability worsening was an increase in EDSS of ≥1.5, for patients with a baseline EDSS of 1 to 5 or ≥5.5, the criterion for disability worsening was an increase in EDSS of ≥1 or ≥0.5, respectively. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2301 to address this endpoint.
Time Frame Baseline, every 3 months up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set from combined studies
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 944 932
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 18- from Kaplan Meier estimates
7.8
(6.2 to 9.7)
10.7
(8.9 to 13.0)
Month 24 - from Kaplan Meier estimates
8.1
(6.5 to 10.2)
12.0
(9.9 to 14.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OMB 20 mg, TER 14 mg
Comments This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2301 to address this endpoint.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.012
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.676
Confidence Interval (2-Sided) 95%
0.498 to 0.917
Estimation Comments [Not Specified]
5.Secondary Outcome
Title 6-month Confirmed Disability Worsening (6mCDW) Based on EDSS - Study COMB157G2302
Hide Description A 6-month confirmed disability worsening (6mCDW) was defined as an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at least 6 months. For patients with a baseline EDSS of 0, the criterion for disability worsening was an increase in EDSS of ≥1.5, for patients with a baseline EDSS of 1 to 5 or ≥5.5, the criterion for disability worsening was an increase in EDSS of ≥1 or ≥0.5, respectively. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2301 to address this endpoint.
Time Frame Baseline, every 3 months up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 479 473
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 18- from Kaplan Meier estimates
8.0
(5.9 to 11.0)
10.0
(7.5 to 13.2)
Month 24 - from Kaplan Meier estimates
8.0
(5.9 to 11.0)
10.9
(8.2 to 14.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OMB 20 mg, TER 14 mg
Comments This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2301 to address this endpoint.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.215
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.759
Confidence Interval (2-Sided) 95%
0.490 to 1.174
Estimation Comments [Not Specified]
6.Secondary Outcome
Title 6-month Confirmed Disability Improvement (6mCDI ) Based on EDSS - Pooled Data
Hide Description A 6-month confirmed disability improvement (6mCDI) was defined as a decrease from baseline EDSS sustained for at least 6 months. For patients with a baseline EDSS of 0 to 1.5, no disability improvement was possible based on the protocol definition of an improvement; for patients with a baseline EDSS of ≥2 to 6 or ≥6.5 to 9.5, the criterion for disability improvement was a decrease in EDSS of ≤1 or ≤0.5, respectively. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2301 to address this endpoint.
Time Frame Baseline, every 3 months up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set from combined studies
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 749 724
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 18 - from Kaplan Meier estimates Number Analyzed 749 participants 723 participants
10.1
(8.1 to 12.6)
7.6
(5.8 to 9.8)
Month 24 - from Kaplan Meier estimates Number Analyzed 749 participants 723 participants
11.0
(8.8 to 13.7)
8.2
(6.3 to 10.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OMB 20 mg, TER 14 mg
Comments This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2301 to address this endpoint.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.092
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.355
Confidence Interval (2-Sided) 95%
0.952 to 1.928
Estimation Comments [Not Specified]
7.Secondary Outcome
Title 6-month Confirmed Disability Improvement (6mCDI ) Based on EDSS - Study COMB157G2302
Hide Description A 6-month confirmed disability improvement (6mCDI) was defined as a decrease from baseline EDSS sustained for at least 6 months. For patients with a baseline EDSS of 0 to 1.5, no disability improvement was possible based on the protocol definition of an improvement; for patients with a baseline EDSS of ≥2 to 6 or ≥6.5 to 9.5, the criterion for disability improvement was a decrease in EDSS of ≤1 or ≤0.5, respectively. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2301 to address this endpoint.
Time Frame Baseline, every 3 months up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 374 361
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 18 - from Kaplan Meier estimates
11.1
(8.2 to 14.8)
8.1
(5.6 to 11.6)
Month 24 - from Kaplan Meier estimates
12.3
(9.1 to 16.5)
8.1
(5.6 to 11.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OMB 20 mg, TER 14 mg
Comments This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2301 to address this endpoint.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.090
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.523
Confidence Interval (2-Sided) 95%
0.936 to 2.477
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Number of Gadolinium-enhancing T1 Lesions Per MRI Scan
Hide Description Total number of Gd-enhancing T1 lesions across all scans per patient adjusted for different number of scans due to variable follow-up time in study.
Time Frame Baseline, yearly up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 438 433
Mean (95% Confidence Interval)
Unit of Measure: lesions per scan
0.0317
(0.021 to 0.048)
0.5172
(0.404 to 0.662)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OMB 20 mg, TER 14 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method negative binomial regression model
Comments [Not Specified]
Method of Estimation Estimation Parameter rate ratio
Estimated Value 0.061
Confidence Interval (2-Sided) 95%
0.037 to 0.101
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Number of New or Enlarging T2 Lesions on MRI Per Year (Annualized Lesion Rate)
Hide Description Number of new/enlarging T2 lesions on last available MRI scan compared to baseline adjusted for different time of scans versus baseline due to variable follow up time in study
Time Frame Baseline, yearly up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 448 442
Mean (95% Confidence Interval)
Unit of Measure: T2 lesions per year
Month 12 n=422,410 Number Analyzed 422 participants 410 participants
0.94
(0.80 to 1.11)
4.41
(3.83 to 5.08)
Month 24 n=90,76 Number Analyzed 90 participants 76 participants
0.72
(0.51 to 1.02)
3.72
(2.68 to 5.18)
EOS n=448,442 Number Analyzed 448 participants 442 participants
0.64
(0.55 to 0.75)
4.16
(3.64 to 4.75)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OMB 20 mg, TER 14 mg
Comments Month 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method negative binomial regression model
Comments [Not Specified]
Method of Estimation Estimation Parameter rate ratio
Estimated Value 0.21
Confidence Interval (2-Sided) 95%
0.17 to 0.27
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection OMB 20 mg, TER 14 mg
Comments Month 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method negative binomial regression model
Comments [Not Specified]
Method of Estimation Estimation Parameter rate ratio
Estimated Value 0.19
Confidence Interval (2-Sided) 95%
0.12 to 0.31
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection OMB 20 mg, TER 14 mg
Comments End of Study
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method negative binomial regression model
Comments [Not Specified]
Method of Estimation Estimation Parameter rate ratio
Estimated Value 0.15
Confidence Interval (2-Sided) 95%
0.13 to 0.19
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Neurofilament Light Chain (NfL) Concentration in Serum
Hide Description The NfL concentration (geometric mean concentration) was estimated by treatment and time point with using a repeated measures model on the basis of all evaluable log-transformed NfL values.
Time Frame Month 3, 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 425 423
Geometric Mean (95% Confidence Interval)
Unit of Measure: pg/mL
Month 3 n=425,423 Number Analyzed 425 participants 423 participants
8.92
(8.62 to 9.23)
10.02
(9.68 to 10.36)
Month 12 n=406,406 Number Analyzed 406 participants 406 participants
7.06
(6.77 to 7.37)
9.53
(9.13 to 9.95)
Month 24 n=345,349 Number Analyzed 345 participants 349 participants
6.80
(6.47 to 7.13)
8.99
(8.57 to 9.44)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OMB 20 mg, TER 14 mg
Comments Month 3
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed Models for Repeated Measures (MMRM)
Method of Estimation Estimation Parameter Geo-mean ratio
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.85 to 0.93
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection OMB 20 mg, TER 14 mg
Comments Month 12
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed Models for Repeated Measures (MMRM)
Method of Estimation Estimation Parameter Geo-mean ratio
Estimated Value 0.74
Confidence Interval (2-Sided) 95%
0.70 to 0.79
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection OMB 20 mg, TER 14 mg
Comments Month 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed Models for Repeated Measures (MMRM)
Method of Estimation Estimation Parameter Geo-mean ratio
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
0.71 to 0.81
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Annualized Rate of Brain Volume Loss Based on Assessments of Percent Brain Volume Change From Baseline
Hide Description Percent change from baseline in brain volume loss (BVL) on all MRI scans adjusted for different time of scan versus baseline due to variable follow up time in study
Time Frame Baseline, Months 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 437 433
Mean (95% Confidence Interval)
Unit of Measure: percentage of brain volume loss
-0.29
(-0.35 to -0.23)
-0.35
(-0.42 to -0.29)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OMB 20 mg, TER 14 mg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.128
Comments [Not Specified]
Method random coefficient model
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
-0.02 to 0.15
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Participants With Confirmed Relapse
Hide Description A confirmed MS relapse was defined as one accompanied by a clinically-relevant change in the EDSS performed by the Independent EDSS rater, i.e. an increase of at least 0.5 points on the EDSS score, or an increase of 1 point on two functional scores or 2 points on one functional score (excluding changes involving bowel/bladder or cerebral functional system).
Time Frame Baseline up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 469 470
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
16.51
(13.18 to 20.57)
32.68
(28.10 to 37.79)
13.Secondary Outcome
Title Annualized Relapse Rate (ARR) >8 Weeks After Onset of Treatment
Hide Description ARR was the number of confirmed relapses in a year, calculated as the total number of relapses for all participants in the treatment group divided by the total participant-years of time in study. A confirmed MS relapse was defined as one accompanied by a clinically-relevant change in the EDSS performed by the Independent EDSS rater, i.e. an increase of at least 0.5 points on the EDSS score, or an increase of 1 point on two functional scores or 2 points on one functional score (excluding changes involving bowel/bladder or cerebral functional system). Comparisons were made to the previous rating (the last EDSS rating that did not occur during a relapse).
Time Frame Baseline up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 461 467
Mean (95% Confidence Interval)
Unit of Measure: number of relapses in a year
0.096
(0.05 to 0.14)
0.241
(0.16 to 0.32)
14.Secondary Outcome
Title 3-month Confirmed Disability Worsening (3mCDW) Based on EDSS > 8 Weeks After Onset of Treatment - Pooled Data
Hide Description A 3-month confirmed disability worsening (3mCDW) was defined as an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at least 3 months. For patients with a baseline EDSS of 0, the criterion for disability worsening was an increase in EDSS of ≥1.5, for patients with a baseline EDSS of 1 to 5 or ≥5.5, the criterion for disability worsening was an increase in EDSS of ≥1 or ≥0.5, respectively. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2301 to address this endpoint.
Time Frame Baseline up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set from combined studies.
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 944 932
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 18 - from Kaplan Meier estimates
9.4
(7.6 to 11.5)
13.5
(11.4 to 16.0)
Month 24 - from Kaplan Meier estimates
10.9
(8.8 to 13.4)
15.0
(12.6 to 17.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OMB 20 mg, TER 14 mg
Comments This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2301 to address this endpoint.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.641
Confidence Interval (2-Sided) 95%
0.486 to 0.847
Estimation Comments [Not Specified]
15.Secondary Outcome
Title 6-month Confirmed Disability Worsening (6mCDW) Based on EDSS > 8 Weeks After Onset of Treatment - Pooled Data
Hide Description A 6-month confirmed disability worsening (6mCDW) was defined as an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at least 6 months. For patients with a baseline EDSS of 0, the criterion for disability worsening was an increase in EDSS of ≥1.5, for patients with a baseline EDSS of 1 to 5 or ≥5.5, the criterion for disability worsening was an increase in EDSS of ≥1 or ≥0.5, respectively. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2301 to address this endpoint.
Time Frame Baseline up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set from combined studies.
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 944 932
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 18- from Kaplan Meier estimates
7.8
(6.2 to 9.7)
10.7
(8.9 to 13.0)
Month 24 - from Kaplan Meier estimates
8.1
(6.5 to 10.2)
12.0
(9.9 to 14.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection OMB 20 mg, TER 14 mg
Comments This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2301 to address this endpoint.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.657
Confidence Interval (2-Sided) 95%
0.481 to 0.898
Estimation Comments [Not Specified]
16.Secondary Outcome
Title 6-month Confirmed Cognitive Decline on Symbol Digit Modalities Test (SDMT) - Pooled Data
Hide Description A 6-month confirmed cognitive decline was defined as a decrease from baseline of at least 4 points in SDMT score sustained for at least 6 months. Processing speed was measured by the Symbol Digit Modalities Test (SDMT) score. SDMT measures the time to pair abstract symbols with specific numbers. The test requires visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items in 90 seconds. (max=110, min=0). Higher scores indicate improvement. Lower scores indicate worsening. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2301 to address this endpoint
Time Frame Baseline, every 6 months up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set from combined studies
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 930 917
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 18 - from Kaplan Meier estimates
14.3
(12.2 to 16.8)
13.7
(11.5 to 16.1)
Month 24 - from Kaplan Meier estimates
15.4
(13.1 to 18.2)
14.0
(11.8 to 16.6)
17.Secondary Outcome
Title 6-month Confirmed Disability Worsening (6mCDW) or 6-month Confirmed Cognitive Decline (6mCCD) - Pooled Data
Hide Description A 6-month confirmed disability worsening (6mCDW) was defined as an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at least 6 months. For patients with a baseline EDSS of 0, the criterion for disability worsening was an increase in EDSS of ≥1.5, for patients with a baseline EDSS of 1 to 5 or ≥5.5, the criterion for disability worsening was an increase in EDSS of ≥1 or ≥0.5, respectively. A 6-month confirmed cognitive decline (6mCCD) was defined as a 4-point worsening on Symbol Digit Modalities Test (SDMT) sustained for at least 6 months. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2301 to address this endpoint.
Time Frame Baseline up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set from combined studies.
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 941 930
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 18 - from Kaplan Meier estimates
20.5
(18.0 to 23.4)
21.7
(19.1 to 24.6)
Month 24 - from Kaplan Meier estimates
21.4
(18.8 to 24.3)
22.6
(19.9 to 25.7)
18.Secondary Outcome
Title Change in Cognitive Performance Measured by the Symbol Digit Modalities Test (SDMT) - Pooled Data
Hide Description Processing speed is being measured by the Symbol Digit Modalities Test (SDMT) score. SDMT measures the time to pair abstract symbols with specific numbers. The test requires visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items in 90 seconds. (max=110, min=0). Higher scores indicate improvement. Lower scores indicate worsening. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2301 to address this endpoint.
Time Frame Baseline up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set from combined studies.
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 921 909
Mean (95% Confidence Interval)
Unit of Measure: scores
Month 6 n=921,909 Number Analyzed 921 participants 909 participants
1.02
(0.46 to 1.59)
0.64
(0.07 to 1.20)
Month 12 n=879,863 Number Analyzed 879 participants 863 participants
1.82
(1.22 to 2.41)
1.70
(1.10 to 2.30)
Month 18 n=849,808 Number Analyzed 849 participants 808 participants
2.84
(2.24 to 3.45)
2.05
(1.44 to 2.67)
Month 24 n=492,468 Number Analyzed 492 participants 468 participants
3.50
(2.80 to 4.20)
2.39
(1.67 to 3.11)
Month 30 n=156,117 Number Analyzed 156 participants 117 participants
3.53
(2.39 to 4.68)
2.97
(1.67 to 4.28)
19.Secondary Outcome
Title 6-month Confirmed Worsening of at Least 20% in the Timed 25-Foot Walk (T25FW) - Pooled Data
Hide Description The patient is directed to walk 25 feet quickly and safely as possible from one marked end to the other. The time is calculated from the initiation of the patient instructed to begin, until the patient has reached the 25-foot mark. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2301 to address this endpoint.
Time Frame Baseline, every 3 months up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set from combined studies.
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 936 925
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 18 - from Kaplan Meier estimates
11.0
(9.1 to 13.3)
10.4
(8.5 to 12.6)
Month 24 - from Kaplan Meier estimates
11.4
(9.5 to 13.8)
10.6
(8.7 to 12.9)
20.Secondary Outcome
Title 6-month Confirmed Worsening of at Least 20% in the 9-Hole Peg Test (9HPT) - Pooled Data
Hide Description 9-Hole Peg Test is a test of upper limb function. Participants place 9 pegs on pegboard and remove pegs and this is timed for each hand. Time recorded in seconds. Longer time indicates poorer upper limb function. 20% improvement is defined as 20% shorter time in seconds. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2301 to address this endpoint.
Time Frame Baseline, every 6 months up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set from combined studies.
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 932 920
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 18 - from Kaplan Meier estimates
2.9
(2.0 to 4.3)
3.3
(2.3 to 4.8)
Month 24 - from Kaplan Meier estimates
2.9
(2.0 to 4.3)
3.3
(2.3 to 4.8)
21.Secondary Outcome
Title 6-month Confirmed Disability Improvement (6mCDI) Sustained Until End of Study (EOS) as Measured by EDSS - Pooled Data
Hide Description A 6-month confirmed disability improvement (6mCDI) sustained until EOS was defined as a decrease from baseline EDSS sustained until EOS. For patients with a baseline EDSS of 0 to 1.5, no disability improvement was possible based on the protocol definition of an improvement; for patients with a baseline EDSS of ≥2 to 6 or ≥6.5 to 9.5, the criterion for disability improvement was a decrease in EDSS of ≤1 or ≤0.5, respectively. This study was not powered for the analysis of this endpoint individually. It was pre-specified in the study protocol to combine the data from this study with study COMB157G2301 to address this endpoint.
Time Frame Baseline, every 3 months up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set from combined studies.
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 749 724
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 18 - from Kaplan Meier estimates
5.4
(4.0 to 7.4)
4.6
(3.2 to 6.5)
Month 24 - from Kaplan Meier estimates
5.8
(4.2 to 7.8)
4.6
(3.2 to 6.5)
22.Secondary Outcome
Title Number of New or Enlarging T2 Lesions on MRI Per Year From Month 12 Until End of Study (EOS)
Hide Description Number of new/enlarging T2 lesions on the last available MRI scan compared to Month 12 adjusted for different time of scans versus Month 12 due to variable follow up time in study.
Time Frame Month 12 up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 369 348
Mean (95% Confidence Interval)
Unit of Measure: T2 lesions per year
0.13
(0.09 to 0.18)
3.84
(3.19 to 4.62)
23.Secondary Outcome
Title Percent Change in T2 Lesion Volume Relative to Baseline
Hide Description Percent change from baseline in total T2 lesion volume
Time Frame Baseline, Month 12, Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 447 437
Mean (Standard Deviation)
Unit of Measure: percentage change in lesion volume
Month 12 n=447,437 Number Analyzed 447 participants 437 participants
-2.4  (8.66) 10.1  (38.57)
Month 24 n=330,320 Number Analyzed 330 participants 320 participants
-2.6  (9.34) 17.8  (53.48)
24.Secondary Outcome
Title No Evidence of Disease Activity (NEDA-4)
Hide Description NEDA-4 was defined as no 3-month confirmed disability worsening, no confirmed MS relapse, no new or enlarging T2 lesions compared to baseline, and the annualized rate of brain atrophy >-0.04%.
Time Frame Baseline, Month 12, Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set.
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 433 427
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 12 n=433,427 Number Analyzed 433 participants 427 participants
23.8
(19.8 to 27.8)
17.8
(14.2 to 21.4)
Month 24 n=92,78 Number Analyzed 92 participants 78 participants
9.8
(3.7 to 15.9)
5.1
(0.2 to 10.0)
25.Secondary Outcome
Title Multiple Sclerosis Impact Scale (MSIS-29) Physical Impact Score Change From Baseline
Hide Description MSIS-29 is a 29-item, self-administered questionnaire that includes 2 domains, physical and psychological. Responses are captured on a 4-point scale ranging from "not at all" (1) to "extremely" (4), where higher scores reflect greater impact on day to day life.
Time Frame Baseline, every 6 months up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 473 461
Mean (Standard Error)
Unit of Measure: scores on a scale
Month 6 n=473,461 Number Analyzed 473 participants 461 participants
-2.20  (0.652) -0.46  (0.659)
Month 12 n=448,438 Number Analyzed 448 participants 438 participants
-2.47  (0.698) -0.49  (0.704)
Month 18 n=425,409 Number Analyzed 425 participants 409 participants
-2.29  (0.784) 1.53  (0.794)
Month 24 n=235,238 Number Analyzed 235 participants 238 participants
-2.93  (0.904) 0.62  (0.905)
Month 30 n=70,54 Number Analyzed 70 participants 54 participants
-2.49  (1.270) 1.44  (1.397)
26.Secondary Outcome
Title Multiple Sclerosis Impact Scale (MSIS-29) Psychological Impact Score Change From Baseline
Hide Description MSIS-29 is a 29-item, self-administered questionnaire that includes 2 domains, physical and psychological. Responses are captured on a 4-point scale ranging from "not at all" (1) to "extremely" (4), where higher scores reflect greater impact on day to day life.
Time Frame Baseline, every 6 months up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 473 461
Mean (Standard Error)
Unit of Measure: scores on a scale
Month 6 n=473,461 Number Analyzed 473 participants 461 participants
-5.96  (0.807) -3.77  (0.816)
Month 12 n=448,436 Number Analyzed 448 participants 436 participants
-5.42  (0.830) -3.88  (0.839)
Month 18 n=423,409 Number Analyzed 423 participants 409 participants
-6.23  (0.884) -2.51  (0.896)
Month 24 n=234,238 Number Analyzed 234 participants 238 participants
-6.10  (1.092) -3.12  (1.090)
Month 30 n=70,54 Number Analyzed 70 participants 54 participants
-6.25  (1.623) -4.75  (1.797)
27.Secondary Outcome
Title Annualized Relapse Rates (ARR) by NfL High-low Subgroups - Pooled Data
Hide Description ARR was the number of confirmed relapses in a year, calculated as the total number of relapses for all participants in the treatment group divided by the total participant-years of time in study. A confirmed MS relapse was defined as one accompanied by a clinically-relevant change in the EDSS performed by the Independent EDSS rater, i.e. an increase of at least 0.5 points on the EDSS score, or an increase of 1 point on two functional scores or 2 points on one functional score (excluding changes involving bowel/bladder or cerebral functional system).
Time Frame Baseline up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Supportive sub-group analysis based on estimations from pooled data from this study and study COMB157G2301.
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 871 841
Mean (95% Confidence Interval)
Unit of Measure: number of relapses in a year
High > median n=443,410 Number Analyzed 443 participants 410 participants
0.08
(0.07 to 0.11)
0.21
(0.17 to 0.26)
Low <= median n=428,431 Number Analyzed 428 participants 431 participants
0.12
(0.09 to 0.15)
0.23
(0.19 to 0.27)
28.Secondary Outcome
Title Number of New or Enlarging T2 Lesions Per Year by NfL High-low Subgroups - Pooled Data
Hide Description Number of new or enlarging T2 lesions on MRI per year (annualized lesion rate).
Time Frame Baseline, yearly up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Supportive sub-group analysis based on estimations from pooled data from this study and study COMB157G2301.
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 850 823
Mean (95% Confidence Interval)
Unit of Measure: T2 lesions per year
High > median n=432,402 Number Analyzed 432 participants 402 participants
0.95
(0.82 to 1.11)
5.28
(4.61 to 6.03)
Low <= median n=418,421 Number Analyzed 418 participants 421 participants
0.39
(0.33 to 0.47)
3.02
(2.64 to 3.46)
29.Secondary Outcome
Title Brain Volume Loss by NfL High-low Subgroups - Pooled Data
Hide Description Percent change from baseline in brain volume loss (BVL) on all MRI scans adjusted for different time of scan versus baseline due to variable follow up time in study.
Time Frame Baseline, Months 12 and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Supportive sub-group analysis based on estimations from pooled data from this study and study COMB157G2301.
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
Overall Number of Participants Analyzed 819 794
Mean (95% Confidence Interval)
Unit of Measure: percentage of brain volume loss
High > median n=416,387 Number Analyzed 416 participants 387 participants
-0.32
(-0.38 to -0.26)
-0.43
(-0.49 to -0.37)
Low <= median n=403,407 Number Analyzed 403 participants 407 participants
-0.24
(-0.30 to -0.18)
-0.29
(-0.35 to -0.22)
30.Secondary Outcome
Title Pharmacokinetic (PK) Concentrations of Ofatumumab
Hide Description Summary statistics of pharmacokinetic (PK) concentrations from trough samples collected within a 7-day window prior or at day of dosing.
Time Frame Baseline, Weeks 4, 12, 24, 48, 96
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Full analysis set
Arm/Group Title OMB 20 mg
Hide Arm/Group Description:
Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily)
Overall Number of Participants Analyzed 481
Mean (Standard Deviation)
Unit of Measure: ug/mL
Baseline n=325 Number Analyzed 325 participants
0.00325  (0.031372)
Week 4 n=346 Number Analyzed 346 participants
1.26512  (0.964645)
Week 12 n=257 Number Analyzed 257 participants
0.20932  (0.287839)
Week 24 n=243 Number Analyzed 243 participants
0.38203  (0.433175)
Week 48 n=240 Number Analyzed 240 participants
0.59087  (0.594490)
Week 96 n=304 Number Analyzed 304 participants
1.13218  (0.991141)
Time Frame Adverse events were reported from first dose of study treatment until last administration of study treatment plus 100 days post treatment, up to maximum duration of approximately 2.7 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title OMB 20mg TER 14mg
Hide Arm/Group Description Ofatumumab 20 mg s.c. injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter (+ teriflunomide-matching placebo capsule orally once daily) Teriflunomide 14 mg capsule orally once daily (+ ofatumumab-matching placebo injections on Days 1, 7, 14, Week 4 and every 4 weeks thereafter)
All-Cause Mortality
OMB 20mg TER 14mg
Affected / at Risk (%) Affected / at Risk (%)
Total   0/481 (0.00%)   1/474 (0.21%) 
Hide Serious Adverse Events
OMB 20mg TER 14mg
Affected / at Risk (%) Affected / at Risk (%)
Total   42/481 (8.73%)   37/474 (7.81%) 
Cardiac disorders     
Bundle branch block bilateral  1  1/481 (0.21%)  0/474 (0.00%) 
Coronary artery disease  1  0/481 (0.00%)  1/474 (0.21%) 
Myocardial infarction  1  1/481 (0.21%)  0/474 (0.00%) 
Nodal arrhythmia  1  1/481 (0.21%)  0/474 (0.00%) 
Bundle branch block bilateral  2  1/481 (0.21%)  0/474 (0.00%) 
Coronary artery disease  2  0/481 (0.00%)  1/474 (0.21%) 
Myocardial infarction  2  1/481 (0.21%)  0/474 (0.00%) 
Nodal arrhythmia  2  1/481 (0.21%)  0/474 (0.00%) 
Eye disorders     
Diplopia  1  0/481 (0.00%)  1/474 (0.21%) 
Diplopia  2  0/481 (0.00%)  1/474 (0.21%) 
Gastrointestinal disorders     
Abdominal pain upper  1  1/481 (0.21%)  0/474 (0.00%) 
Enteritis  1  1/481 (0.21%)  0/474 (0.00%) 
Intestinal obstruction  1  0/481 (0.00%)  1/474 (0.21%) 
Pancreatitis acute  1  1/481 (0.21%)  0/474 (0.00%) 
Umbilical hernia  1  1/481 (0.21%)  0/474 (0.00%) 
Abdominal pain upper  2  1/481 (0.21%)  0/474 (0.00%) 
Enteritis  2  1/481 (0.21%)  0/474 (0.00%) 
Intestinal obstruction  2  0/481 (0.00%)  1/474 (0.21%) 
Pancreatitis acute  2  1/481 (0.21%)  0/474 (0.00%) 
Umbilical hernia  2  1/481 (0.21%)  0/474 (0.00%) 
General disorders     
Drug withdrawal syndrome  1  1/481 (0.21%)  0/474 (0.00%) 
Non-cardiac chest pain  1  0/481 (0.00%)  1/474 (0.21%) 
Pyrexia  1  1/481 (0.21%)  0/474 (0.00%) 
Drug withdrawal syndrome  2  1/481 (0.21%)  0/474 (0.00%) 
Non-cardiac chest pain  2  0/481 (0.00%)  1/474 (0.21%) 
Pyrexia  2  1/481 (0.21%)  0/474 (0.00%) 
Hepatobiliary disorders     
Cholecystitis  1  0/481 (0.00%)  1/474 (0.21%) 
Cholelithiasis  1  2/481 (0.42%)  0/474 (0.00%) 
Hepatic failure  1  0/481 (0.00%)  1/474 (0.21%) 
Cholecystitis  2  0/481 (0.00%)  1/474 (0.21%) 
Cholecystitis acute  2  1/481 (0.21%)  0/474 (0.00%) 
Cholelithiasis  2  2/481 (0.42%)  0/474 (0.00%) 
Hepatic failure  2  0/481 (0.00%)  1/474 (0.21%) 
Infections and infestations     
Appendicitis  1  5/481 (1.04%)  1/474 (0.21%) 
Cystitis  1  0/481 (0.00%)  1/474 (0.21%) 
Gastroenteritis  1  1/481 (0.21%)  0/474 (0.00%) 
Influenza  1  1/481 (0.21%)  0/474 (0.00%) 
Lower respiratory tract infection  1  1/481 (0.21%)  0/474 (0.00%) 
Osteomyelitis  1  0/481 (0.00%)  1/474 (0.21%) 
Paronychia  1  0/481 (0.00%)  1/474 (0.21%) 
Peritonitis  1  0/481 (0.00%)  1/474 (0.21%) 
Pneumonia  1  1/481 (0.21%)  0/474 (0.00%) 
Postoperative abscess  1  0/481 (0.00%)  1/474 (0.21%) 
Respiratory tract infection viral  1  1/481 (0.21%)  0/474 (0.00%) 
Sepsis  1  0/481 (0.00%)  1/474 (0.21%) 
Urinary tract infection  1  2/481 (0.42%)  2/474 (0.42%) 
Urosepsis  1  1/481 (0.21%)  0/474 (0.00%) 
Viral infection  1  0/481 (0.00%)  1/474 (0.21%) 
Appendicitis  2  5/481 (1.04%)  1/474 (0.21%) 
Cystitis  2  0/481 (0.00%)  1/474 (0.21%) 
Gastroenteritis  2  1/481 (0.21%)  0/474 (0.00%) 
Influenza  2  1/481 (0.21%)  0/474 (0.00%) 
Lower respiratory tract infection  2  1/481 (0.21%)  0/474 (0.00%) 
Osteomyelitis  2  0/481 (0.00%)  1/474 (0.21%) 
Paronychia  2  0/481 (0.00%)  1/474 (0.21%) 
Peritonitis  2  0/481 (0.00%)  1/474 (0.21%) 
Pneumonia  2  1/481 (0.21%)  0/474 (0.00%) 
Postoperative abscess  2  0/481 (0.00%)  1/474 (0.21%) 
Respiratory tract infection viral  2  1/481 (0.21%)  0/474 (0.00%) 
Sepsis  2  0/481 (0.00%)  1/474 (0.21%) 
Urinary tract infection  2  2/481 (0.42%)  2/474 (0.42%) 
Urosepsis  2  1/481 (0.21%)  0/474 (0.00%) 
Viral infection  2  0/481 (0.00%)  1/474 (0.21%) 
Injury, poisoning and procedural complications     
Ankle fracture  1  2/481 (0.42%)  0/474 (0.00%) 
Bone contusion  1  0/481 (0.00%)  1/474 (0.21%) 
Concussion  1  1/481 (0.21%)  0/474 (0.00%) 
Craniocerebral injury  1  0/481 (0.00%)  1/474 (0.21%) 
Fall  1  1/481 (0.21%)  1/474 (0.21%) 
Femoral neck fracture  1  0/481 (0.00%)  1/474 (0.21%) 
Head injury  1  0/481 (0.00%)  1/474 (0.21%) 
Humerus fracture  1  1/481 (0.21%)  0/474 (0.00%) 
Incisional hernia  1  0/481 (0.00%)  1/474 (0.21%) 
Joint dislocation  1  1/481 (0.21%)  0/474 (0.00%) 
Ligament sprain  1  0/481 (0.00%)  1/474 (0.21%) 
Post procedural haematoma  1  0/481 (0.00%)  1/474 (0.21%) 
Post procedural inflammation  1  0/481 (0.00%)  1/474 (0.21%) 
Radius fracture  1  0/481 (0.00%)  1/474 (0.21%) 
Rib fracture  1  1/481 (0.21%)  0/474 (0.00%) 
Road traffic accident  1  1/481 (0.21%)  0/474 (0.00%) 
Tendon injury  1  1/481 (0.21%)  0/474 (0.00%) 
Upper limb fracture  1  1/481 (0.21%)  0/474 (0.00%) 
Ankle fracture  2  2/481 (0.42%)  0/474 (0.00%) 
Bone contusion  2  0/481 (0.00%)  1/474 (0.21%) 
Concussion  2  1/481 (0.21%)  0/474 (0.00%) 
Craniocerebral injury  2  0/481 (0.00%)  1/474 (0.21%) 
Fall  2  1/481 (0.21%)  1/474 (0.21%) 
Femoral neck fracture  2  0/481 (0.00%)  1/474 (0.21%) 
Head injury  2  0/481 (0.00%)  1/474 (0.21%) 
Humerus fracture  2  1/481 (0.21%)  0/474 (0.00%) 
Incisional hernia  2  0/481 (0.00%)  1/474 (0.21%) 
Joint dislocation  2  1/481 (0.21%)  0/474 (0.00%) 
Ligament sprain  2  0/481 (0.00%)  1/474 (0.21%) 
Post procedural haematoma  2  0/481 (0.00%)  1/474 (0.21%) 
Post procedural inflammation  2  0/481 (0.00%)  1/474 (0.21%) 
Radius fracture  2  0/481 (0.00%)  1/474 (0.21%) 
Rib fracture  2  1/481 (0.21%)  0/474 (0.00%) 
Road traffic accident  2  1/481 (0.21%)  0/474 (0.00%) 
Tendon injury  2  1/481 (0.21%)  0/474 (0.00%) 
Upper limb fracture  2  1/481 (0.21%)  0/474 (0.00%) 
Musculoskeletal and connective tissue disorders     
Intervertebral disc compression  1  1/481 (0.21%)  0/474 (0.00%) 
Intervertebral disc protrusion  1  1/481 (0.21%)  1/474 (0.21%) 
Neck pain  1  1/481 (0.21%)  0/474 (0.00%) 
Pathological fracture  1  0/481 (0.00%)  1/474 (0.21%) 
Spondylitis  1  1/481 (0.21%)  0/474 (0.00%) 
Intervertebral disc compression  2  1/481 (0.21%)  0/474 (0.00%) 
Intervertebral disc protrusion  2  1/481 (0.21%)  1/474 (0.21%) 
Neck pain  2  1/481 (0.21%)  0/474 (0.00%) 
Pathological fracture  2  0/481 (0.00%)  1/474 (0.21%) 
Spondylitis  2  1/481 (0.21%)  0/474 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Basal cell carcinoma  1  2/481 (0.42%)  1/474 (0.21%) 
Fibroadenoma of breast  1  1/481 (0.21%)  0/474 (0.00%) 
Uterine leiomyoma  1  2/481 (0.42%)  1/474 (0.21%) 
Basal cell carcinoma  2  2/481 (0.42%)  1/474 (0.21%) 
Benign breast neoplasm  2  1/481 (0.21%)  0/474 (0.00%) 
Fibroadenoma of breast  2  1/481 (0.21%)  0/474 (0.00%) 
Uterine leiomyoma  2  2/481 (0.42%)  1/474 (0.21%) 
Nervous system disorders     
Headache  1  1/481 (0.21%)  0/474 (0.00%) 
Lumbar radiculopathy  1  0/481 (0.00%)  1/474 (0.21%) 
Multiple sclerosis  1  0/481 (0.00%)  1/474 (0.21%) 
Multiple sclerosis relapse  1  0/481 (0.00%)  1/474 (0.21%) 
Myelopathy  1  0/481 (0.00%)  1/474 (0.21%) 
Quadriplegia  1  1/481 (0.21%)  0/474 (0.00%) 
Syncope  1  2/481 (0.42%)  0/474 (0.00%) 
Trigeminal neuralgia  1  1/481 (0.21%)  0/474 (0.00%) 
Headache  2  2/481 (0.42%)  0/474 (0.00%) 
Lumbar radiculopathy  2  0/481 (0.00%)  1/474 (0.21%) 
Multiple sclerosis  2  0/481 (0.00%)  1/474 (0.21%) 
Multiple sclerosis relapse  2  1/481 (0.21%)  1/474 (0.21%) 
Myelopathy  2  0/481 (0.00%)  1/474 (0.21%) 
Quadriparesis  2  1/481 (0.21%)  0/474 (0.00%) 
Syncope  2  2/481 (0.42%)  0/474 (0.00%) 
Trigeminal neuralgia  2  1/481 (0.21%)  0/474 (0.00%) 
Psychiatric disorders     
Anxiety  1  0/481 (0.00%)  1/474 (0.21%) 
Depression  1  0/481 (0.00%)  1/474 (0.21%) 
Major depression  1  0/481 (0.00%)  1/474 (0.21%) 
Suicidal ideation  1  1/481 (0.21%)  0/474 (0.00%) 
Suicide attempt  1  0/481 (0.00%)  1/474 (0.21%) 
Anxiety  2  0/481 (0.00%)  1/474 (0.21%) 
Depression  2  0/481 (0.00%)  1/474 (0.21%) 
Major depression  2  0/481 (0.00%)  1/474 (0.21%) 
Suicidal ideation  2  1/481 (0.21%)  0/474 (0.00%) 
Suicide attempt  2  0/481 (0.00%)  1/474 (0.21%) 
Renal and urinary disorders     
Urinary retention  1  0/481 (0.00%)  1/474 (0.21%) 
Urinary retention  2  0/481 (0.00%)  1/474 (0.21%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  0/481 (0.00%)  1/474 (0.21%) 
Testicular infarction  1  1/481 (0.21%)  0/474 (0.00%) 
Uterine haemorrhage  1  0/481 (0.00%)  1/474 (0.21%) 
Uterine polyp  1  0/481 (0.00%)  2/474 (0.42%) 
Uterovaginal prolapse  1  0/481 (0.00%)  1/474 (0.21%) 
Benign prostatic hyperplasia  2  0/481 (0.00%)  1/474 (0.21%) 
Testicular infarction  2  1/481 (0.21%)  0/474 (0.00%) 
Uterine haemorrhage  2  0/481 (0.00%)  1/474 (0.21%) 
Uterine polyp  2  0/481 (0.00%)  2/474 (0.42%) 
Uterovaginal prolapse  2  0/481 (0.00%)  1/474 (0.21%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary embolism  1  0/481 (0.00%)  1/474 (0.21%) 
Pulmonary sarcoidosis  1  1/481 (0.21%)  0/474 (0.00%) 
Pulmonary embolism  2  0/481 (0.00%)  1/474 (0.21%) 
Pulmonary sarcoidosis  2  1/481 (0.21%)  0/474 (0.00%) 
Skin and subcutaneous tissue disorders     
Angioedema  1  1/481 (0.21%)  0/474 (0.00%) 
Angioedema  2  1/481 (0.21%)  0/474 (0.00%) 
Lichen sclerosus  2  0/481 (0.00%)  1/474 (0.21%) 
Vascular disorders     
Aortic dissection  1  0/481 (0.00%)  1/474 (0.21%) 
Deep vein thrombosis  1  0/481 (0.00%)  1/474 (0.21%) 
Aortic dissection  2  0/481 (0.00%)  1/474 (0.21%) 
Deep vein thrombosis  2  1/481 (0.21%)  1/474 (0.21%) 
1
Term from vocabulary, MedDRA (22.0)
2
Term from vocabulary, MedDRA (23.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
OMB 20mg TER 14mg
Affected / at Risk (%) Affected / at Risk (%)
Total   348/481 (72.35%)   322/474 (67.93%) 
Gastrointestinal disorders     
Diarrhoea  1  28/481 (5.82%)  49/474 (10.34%) 
Nausea  1  30/481 (6.24%)  32/474 (6.75%) 
Diarrhoea  2  28/481 (5.82%)  49/474 (10.34%) 
Nausea  2  30/481 (6.24%)  32/474 (6.75%) 
General disorders     
Fatigue  1  25/481 (5.20%)  32/474 (6.75%) 
Injection site reaction  1  61/481 (12.68%)  26/474 (5.49%) 
Fatigue  2  25/481 (5.20%)  32/474 (6.75%) 
Injection site reaction  2  61/481 (12.68%)  26/474 (5.49%) 
Infections and infestations     
Influenza  1  30/481 (6.24%)  30/474 (6.33%) 
Nasopharyngitis  1  88/481 (18.30%)  87/474 (18.35%) 
Upper respiratory tract infection  1  49/481 (10.19%)  47/474 (9.92%) 
Urinary tract infection  1  54/481 (11.23%)  35/474 (7.38%) 
Influenza  2  27/481 (5.61%)  28/474 (5.91%) 
Nasopharyngitis  2  88/481 (18.30%)  88/474 (18.57%) 
Upper respiratory tract infection  2  52/481 (10.81%)  47/474 (9.92%) 
Urinary tract infection  2  55/481 (11.43%)  34/474 (7.17%) 
Injury, poisoning and procedural complications     
Injection related reaction  1  119/481 (24.74%)  66/474 (13.92%) 
Injection related reaction  2  119/481 (24.74%)  66/474 (13.92%) 
Investigations     
Blood immunoglobulin M decreased  1  30/481 (6.24%)  8/474 (1.69%) 
Blood immunoglobulin M decreased  2  31/481 (6.44%)  8/474 (1.69%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  35/481 (7.28%)  24/474 (5.06%) 
Pain in extremity  1  23/481 (4.78%)  30/474 (6.33%) 
Arthralgia  2  30/481 (6.24%)  25/474 (5.27%) 
Back pain  2  35/481 (7.28%)  24/474 (5.06%) 
Pain in extremity  2  22/481 (4.57%)  30/474 (6.33%) 
Nervous system disorders     
Headache  1  68/481 (14.14%)  65/474 (13.71%) 
Headache  2  69/481 (14.35%)  66/474 (13.92%) 
Psychiatric disorders     
Anxiety  1  28/481 (5.82%)  17/474 (3.59%) 
Depression  1  24/481 (4.99%)  24/474 (5.06%) 
Anxiety  2  30/481 (6.24%)  17/474 (3.59%) 
Depression  2  23/481 (4.78%)  24/474 (5.06%) 
Respiratory, thoracic and mediastinal disorders     
Cough  2  17/481 (3.53%)  24/474 (5.06%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  27/481 (5.61%)  74/474 (15.61%) 
Alopecia  2  27/481 (5.61%)  75/474 (15.82%) 
Vascular disorders     
Hypertension  1  20/481 (4.16%)  31/474 (6.54%) 
Hypertension  2  20/481 (4.16%)  32/474 (6.75%) 
1
Term from vocabulary, MedDRA (22.0)
2
Term from vocabulary, MedDRA (23.1)
Indicates events were collected by systematic assessment
This study was not powered for the analysis of some secondary endpoints as a stand-alone study. It was pre-specified in the study protocol to combine the data with study COMB157G2301 to address these endpoints.
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.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: Novartis.email@novartis.com
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02792231    
Other Study ID Numbers: COMB157G2302
2015-005419-33 ( EudraCT Number )
First Submitted: June 2, 2016
First Posted: June 7, 2016
Results First Submitted: September 18, 2020
Results First Posted: October 19, 2020
Last Update Posted: November 22, 2021