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

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ClinicalTrials.gov Identifier: NCT02792218
Recruitment Status : Completed
First Posted : June 7, 2016
Results First Posted : October 19, 2020
Last Update Posted : July 13, 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 Sclerosis
Interventions Drug: Ofatumumab subcutaneous injection
Drug: Teriflunomide-matching placebo capsules
Drug: Teriflunomide capsule
Drug: Matching placebo of ofatumumab subcutaneous injections
Enrollment 930
Recruitment Details  
Pre-assignment Details A total of 1277 patients were screened, of whom 927 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 465 462
On Study Drug at Interim Cut Off [1] 400 359
Off Study Drug at Interim Cut Off [2] 16 17
Completed 416 376
Not Completed 49 86
Reason Not Completed
Patient/guardian decision             16             42
Adverse Event             14             14
Lost to Follow-up             10             5
Lack of Efficacy             1             12
Physician Decision             3             4
Protocol deviation             3             2
New therapy for study indication             0             1
Non-compliance with study treatment             0             1
Pregnancy             1             0
Ongoing at interim cutoff             1             5
[1]
Patients who took study drug until the treatment epoch completion
[2]
Patients who completed the treatment epoch but discontinued study drug prematurely
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 465 462 927
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 465 participants 462 participants 927 participants
38.9  (8.77) 37.8  (8.95) 38.4  (8.87)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 465 participants 462 participants 927 participants
Female
318
  68.4%
317
  68.6%
635
  68.5%
Male
147
  31.6%
145
  31.4%
292
  31.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Asian Number Analyzed 465 participants 462 participants 927 participants
15
   3.2%
16
   3.5%
31
   3.3%
Black or African American Number Analyzed 465 participants 462 participants 927 participants
15
   3.2%
20
   4.3%
35
   3.8%
White Number Analyzed 465 participants 462 participants 927 participants
411
  88.4%
412
  89.2%
823
  88.8%
Other Number Analyzed 465 participants 462 participants 927 participants
22
   4.7%
14
   3.0%
36
   3.9%
Unknown Number Analyzed 465 participants 462 participants 927 participants
2
   0.4%
0
   0.0%
2
   0.2%
Number of relapses in the past 12 months prior to screening   [1] 
Mean (Standard Deviation)
Unit of measure:  Number of relapses
Number Analyzed 465 participants 462 participants 927 participants
1.2  (0.63) 1.3  (0.69) 1.2  (0.66)
[1]
Measure Description: Appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event
Expanded Disability Status Scale (EDSS)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 465 participants 461 participants 926 participants
2.97  (1.357) 2.94  (1.355) 2.96  (1.356)
[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 Gd-enhancing T1 lesions   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  T1 lesions
Number Analyzed 454 participants 452 participants 906 participants
1.7  (4.93) 1.2  (2.58) 1.5  (3.95)
[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) (Confirmed Relapses)
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 454 452
Mean (95% Confidence Interval)
Unit of Measure: number of relapses in a year
0.11
(0.09 to 0.14)
0.22
(0.18 to 0.26)
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 0.495
Confidence Interval (2-Sided) 95%
0.374 to 0.654
Estimation Comments [Not Specified]
2.Secondary Outcome
Title 3-month Confirmed Disability Worsening (3mCDW) Based on EDSS
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.
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 465 459
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 18 - from Kaplan Meier estimates
9.4
(7.0 to 12.6)
13.9
(10.0 to 17.5)
Month 24 - from Kaplan Meier estimates
13.9
(10.9 to 17.5)
15.4
(12.1 to 19.4)
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 COMB157G2302 to address this endpoint.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.029
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.652
Confidence Interval (2-Sided) 95%
0.445 to 0.957
Estimation Comments [Not Specified]
3.Secondary Outcome
Title 6-month Confirmed Disability Worsening (6mCDW) Based on EDSS
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.
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 465 459
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 18- from Kaplan Meier estimates
7.5
(5.4 to 10.4)
11.5
(8.9 to 14.9)
Month 24 - from Kaplan Meier estimates
8.2
(6.0 to 11.3)
13.0
(10.0 to 16.9)
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 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 COMB157G2302 to address this endpoint.
Statistical Test of Hypothesis P-Value 0.022
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.607
Confidence Interval (2-Sided) 95%
0.396 to 0.930
Estimation Comments [Not Specified]
4.Secondary Outcome
Title 6-month Confirmed Disability Improvement (6mCDI ) Based on EDSS
Hide Description A 6-month confirmed disability improvement is a decrease from baseline in Expanded Disability Status Scale (EDSS) score sustained for at least 6 months.
Time Frame Baseline, every 3 months up to 2.5 years
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
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 375 363
Mean (95% Confidence Interval)
Unit of Measure: percentage of participants
Month 18 - from Kaplan Meier estimates
9.1
(6.5 to 12.7)
7.1
(4.8 to 10.3)
Month 24 - from Kaplan Meier estimates
9.7
(7.0 to 13.5)
8.2
(5.6 to 11.9)
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 COMB157G2302 to address this endpoint.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.515
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.186
Confidence Interval (2-Sided) 95%
0.709 to 1.984
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Number of Gd-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 432 422
Mean (95% Confidence Interval)
Unit of Measure: lesions per scan
0.0115
(0.006 to 0.022)
0.4523
(0.356 to 0.575)
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 0.025
Confidence Interval (2-Sided) 95%
0.013 to 0.049
Estimation Comments [Not Specified]
6.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 440 431
Mean (95% Confidence Interval)
Unit of Measure: T2 lesions per year
Month 12 n=420,407 Number Analyzed 420 participants 407 participants
1.13
(0.95 to 1.33)
4.30
(3.71 to 4.98)
Month 24 n=103,93 Number Analyzed 103 participants 93 participants
0.72
(0.53 to 0.98)
3.21
(2.42 to 4.24)
EOS n=440,431 Number Analyzed 440 participants 431 participants
0.72
(0.61 to 0.85)
4.00
(3.47 to 4.61)
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 0.26
Confidence Interval (2-Sided) 95%
0.21 to 0.33
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 0.22
Confidence Interval (2-Sided) 95%
0.15 to 0.34
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 0.18
Confidence Interval (2-Sided) 95%
0.15 to 0.22
Estimation Comments [Not Specified]
7.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 430 404
Geometric Mean (95% Confidence Interval)
Unit of Measure: pg/mL
Month 3 n=430,404 Number Analyzed 430 participants 404 participants
8.80
(8.48 to 9.12)
9.41
(9.06 to 9.77)
Month 12 n=414,399 Number Analyzed 414 participants 399 participants
7.02
(6.73 to 7.32)
9.62
(9.22 to 10.05)
Month 24 n=371,350 Number Analyzed 371 participants 350 participants
6.90
(6.57 to 7.24)
8.99
(8.55 to 9.45)
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 0.011
Comments [Not Specified]
Method Mixed Models Analysis
Comments Mixed Models for Repeated Measures (MMRM)
Method of Estimation Estimation Parameter Geo-mean ratio
Estimated Value 0.93
Confidence Interval (2-Sided) 95%
0.89 to 0.98
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 0.73
Confidence Interval (2-Sided) 95%
0.69 to 0.77
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 0.77
Confidence Interval (2-Sided) 95%
0.72 to 0.82
Estimation Comments [Not Specified]
8.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 369 352
Mean (95% Confidence Interval)
Unit of Measure: percentage of brain volume loss
-0.28
(-0.34 to 0.22)
-0.35
(-0.41 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 0.116
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]
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 OMB 20mg TER 14mg
All-Cause Mortality
OMB 20mg TER 14mg
Affected / at Risk (%) Affected / at Risk (%)
Total   0/465 (0.00%)   0/462 (0.00%) 
Hide Serious Adverse Events
OMB 20mg TER 14mg
Affected / at Risk (%) Affected / at Risk (%)
Total   48/465 (10.32%)   38/462 (8.23%) 
Blood and lymphatic system disorders     
Anaemia  1  1/465 (0.22%)  0/462 (0.00%) 
Leukopenia  1  1/465 (0.22%)  0/462 (0.00%) 
Ear and labyrinth disorders     
Deafness neurosensory  1  1/465 (0.22%)  0/462 (0.00%) 
Vertigo  1  2/465 (0.43%)  0/462 (0.00%) 
Gastrointestinal disorders     
Abdominal pain upper  1  0/465 (0.00%)  2/462 (0.43%) 
Diarrhoea  1  0/465 (0.00%)  1/462 (0.22%) 
Duodenal ulcer  1  1/465 (0.22%)  0/462 (0.00%) 
Intestinal polyp  1  1/465 (0.22%)  0/462 (0.00%) 
Large intestine polyp  1  1/465 (0.22%)  0/462 (0.00%) 
Nausea  1  0/465 (0.00%)  1/462 (0.22%) 
Obstructive pancreatitis  1  1/465 (0.22%)  0/462 (0.00%) 
Pancreatitis  1  0/465 (0.00%)  1/462 (0.22%) 
Vomiting  1  0/465 (0.00%)  1/462 (0.22%) 
General disorders     
Injection site reaction  1  1/465 (0.22%)  0/462 (0.00%) 
Hepatobiliary disorders     
Biliary colic  1  1/465 (0.22%)  0/462 (0.00%) 
Cholecystitis  1  1/465 (0.22%)  0/462 (0.00%) 
Cholecystitis acute  1  0/465 (0.00%)  1/462 (0.22%) 
Cholecystitis chronic  1  1/465 (0.22%)  0/462 (0.00%) 
Cholelithiasis migration  1  1/465 (0.22%)  0/462 (0.00%) 
Immune system disorders     
Anaphylactic reaction  1  1/465 (0.22%)  0/462 (0.00%) 
Infections and infestations     
Abscess sweat gland  1  0/465 (0.00%)  1/462 (0.22%) 
Appendicitis  1  3/465 (0.65%)  1/462 (0.22%) 
Campylobacter infection  1  0/465 (0.00%)  1/462 (0.22%) 
Cystitis  1  1/465 (0.22%)  0/462 (0.00%) 
Escherichia urinary tract infection  1  1/465 (0.22%)  0/462 (0.00%) 
Gastroenteritis  1  2/465 (0.43%)  0/462 (0.00%) 
Influenza  1  1/465 (0.22%)  0/462 (0.00%) 
Kidney infection  1  1/465 (0.22%)  0/462 (0.00%) 
Neutropenic sepsis  1  1/465 (0.22%)  0/462 (0.00%) 
Osteomyelitis  1  1/465 (0.22%)  0/462 (0.00%) 
Pneumonia  1  0/465 (0.00%)  1/462 (0.22%) 
Pneumonia influenzal  1  0/465 (0.00%)  1/462 (0.22%) 
Salpingo-oophoritis  1  0/465 (0.00%)  1/462 (0.22%) 
Tick-borne viral encephalitis  1  0/465 (0.00%)  1/462 (0.22%) 
Upper respiratory tract infection  1  1/465 (0.22%)  0/462 (0.00%) 
Urinary tract infection  1  1/465 (0.22%)  0/462 (0.00%) 
Injury, poisoning and procedural complications     
Fibula fracture  1  1/465 (0.22%)  0/462 (0.00%) 
Injection related reaction  1  2/465 (0.43%)  0/462 (0.00%) 
Intentional overdose  1  1/465 (0.22%)  0/462 (0.00%) 
Ligament rupture  1  1/465 (0.22%)  0/462 (0.00%) 
Meniscus injury  1  1/465 (0.22%)  0/462 (0.00%) 
Tibia fracture  1  0/465 (0.00%)  1/462 (0.22%) 
Ulna fracture  1  1/465 (0.22%)  0/462 (0.00%) 
Investigations     
Liver function test increased  1  1/465 (0.22%)  0/462 (0.00%) 
Psychiatric evaluation  1  1/465 (0.22%)  0/462 (0.00%) 
Weight decreased  1  0/465 (0.00%)  1/462 (0.22%) 
Metabolism and nutrition disorders     
Dehydration  1  0/465 (0.00%)  1/462 (0.22%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  2/465 (0.43%)  1/462 (0.22%) 
Femoroacetabular impingement  1  1/465 (0.22%)  0/462 (0.00%) 
Intervertebral disc protrusion  1  0/465 (0.00%)  1/462 (0.22%) 
Jaw cyst  1  0/465 (0.00%)  1/462 (0.22%) 
Joint range of motion decreased  1  0/465 (0.00%)  1/462 (0.22%) 
Morphoea  1  0/465 (0.00%)  1/462 (0.22%) 
Muscle spasms  1  1/465 (0.22%)  0/462 (0.00%) 
Synovial cyst  1  0/465 (0.00%)  1/462 (0.22%) 
Synovitis  1  0/465 (0.00%)  1/462 (0.22%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cervix carcinoma  1  0/465 (0.00%)  1/462 (0.22%) 
Fibrosarcoma  1  0/465 (0.00%)  1/462 (0.22%) 
Invasive breast carcinoma  1  1/465 (0.22%)  0/462 (0.00%) 
Malignant melanoma in situ  1  1/465 (0.22%)  0/462 (0.00%) 
Non-Hodgkin's lymphoma recurrent  1  1/465 (0.22%)  0/462 (0.00%) 
Uterine leiomyoma  1  1/465 (0.22%)  0/462 (0.00%) 
Nervous system disorders     
Cerebellar ischaemia  1  0/465 (0.00%)  1/462 (0.22%) 
Cervicobrachial syndrome  1  0/465 (0.00%)  1/462 (0.22%) 
Dizziness  1  1/465 (0.22%)  0/462 (0.00%) 
Hemiplegic migraine  1  0/465 (0.00%)  1/462 (0.22%) 
Hypoaesthesia  1  0/465 (0.00%)  1/462 (0.22%) 
Lumbosacral radiculopathy  1  1/465 (0.22%)  0/462 (0.00%) 
Multiple sclerosis relapse  1  1/465 (0.22%)  4/462 (0.87%) 
Paraesthesia  1  0/465 (0.00%)  1/462 (0.22%) 
Syncope  1  0/465 (0.00%)  1/462 (0.22%) 
Trigeminal neuralgia  1  0/465 (0.00%)  1/462 (0.22%) 
Psychiatric disorders     
Depression  1  1/465 (0.22%)  0/462 (0.00%) 
Depression suicidal  1  1/465 (0.22%)  0/462 (0.00%) 
Mental status changes  1  1/465 (0.22%)  0/462 (0.00%) 
Psychotic disorder  1  1/465 (0.22%)  0/462 (0.00%) 
Somatic symptom disorder  1  1/465 (0.22%)  0/462 (0.00%) 
Stress  1  1/465 (0.22%)  0/462 (0.00%) 
Suicidal ideation  1  2/465 (0.43%)  0/462 (0.00%) 
Suicide attempt  1  1/465 (0.22%)  0/462 (0.00%) 
Renal and urinary disorders     
Nephrolithiasis  1  0/465 (0.00%)  2/462 (0.43%) 
Urinary retention  1  0/465 (0.00%)  1/462 (0.22%) 
Reproductive system and breast disorders     
Adnexa uteri cyst  1  1/465 (0.22%)  0/462 (0.00%) 
Cervical dysplasia  1  1/465 (0.22%)  0/462 (0.00%) 
Menorrhagia  1  1/465 (0.22%)  1/462 (0.22%) 
Metrorrhagia  1  0/465 (0.00%)  1/462 (0.22%) 
Uterine polyp  1  0/465 (0.00%)  1/462 (0.22%) 
Respiratory, thoracic and mediastinal disorders     
Pneumonia aspiration  1  0/465 (0.00%)  1/462 (0.22%) 
Pulmonary embolism  1  0/465 (0.00%)  2/462 (0.43%) 
Pulmonary sarcoidosis  1  1/465 (0.22%)  0/462 (0.00%) 
Vascular disorders     
Thrombophlebitis  1  0/465 (0.00%)  1/462 (0.22%) 
1
Term from vocabulary, MedDRA (22.0)
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   277/465 (59.57%)   303/462 (65.58%) 
Gastrointestinal disorders     
Diarrhoea  1  21/465 (4.52%)  61/462 (13.20%) 
Nausea  1  31/465 (6.67%)  31/462 (6.71%) 
General disorders     
Fatigue  1  46/465 (9.89%)  40/462 (8.66%) 
Injection site reaction  1  41/465 (8.82%)  26/462 (5.63%) 
Infections and infestations     
Influenza  1  32/465 (6.88%)  29/462 (6.28%) 
Nasopharyngitis  1  82/465 (17.63%)  69/462 (14.94%) 
Upper respiratory tract infection  1  47/465 (10.11%)  73/462 (15.80%) 
Urinary tract infection  1  41/465 (8.82%)  41/462 (8.87%) 
Injury, poisoning and procedural complications     
Injection related reaction  1  74/465 (15.91%)  77/462 (16.67%) 
Investigations     
Blood immunoglobulin M decreased  1  26/465 (5.59%)  13/462 (2.81%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  25/465 (5.38%)  23/462 (4.98%) 
Back pain  1  35/465 (7.53%)  33/462 (7.14%) 
Pain in extremity  1  23/465 (4.95%)  36/462 (7.79%) 
Nervous system disorders     
Headache  1  57/465 (12.26%)  51/462 (11.04%) 
Paraesthesia  1  16/465 (3.44%)  30/462 (6.49%) 
Psychiatric disorders     
Depression  1  21/465 (4.52%)  24/462 (5.19%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  27/465 (5.81%)  64/462 (13.85%) 
Vascular disorders     
Hypertension  1  15/465 (3.23%)  24/462 (5.19%) 
1
Term from vocabulary, MedDRA (22.0)
Indicates events were collected by systematic assessment
This study was not powered for the analysis of disability-related key secondary endpoints as a stand alone study. It was pre-specified in the study protocol to combine the data for 3mCDW, 6mCDW and 6mCDI from this study with study COMB157G2302
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: NCT02792218    
Other Study ID Numbers: COMB157G2301
2015-005418-31 ( 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: July 13, 2021