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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 : Active, not recruiting
First Posted : June 7, 2016
Results First Posted : October 19, 2020
Last Update Posted : October 20, 2020
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 957
Recruitment Details  
Pre-assignment Details There were 1280 patients screened
Arm/Group Title OMB 20 mg TER 14 mg
Hide Arm/Group Description Ofatumumab 20 mg pre-filled syringes for subcutaneous injectionon on days 1 ,7 ,14, week 4 and every 4 weeks thereafter and a teriflunomide- matching placebo, taken orally once daily Teriflunomide 14 mg oral capsule taken once daily and matching placebo for subcutaneous injections to ofatumumab on days 1, 7, 14, week 4 and every 4 weeks thereafter
Period Title: Overall Study
Started 481 474
On Study Drug at Interim Cut Off 383 370
Off Study Drug at Interim Cut Off 14 19
Completed 397 389
Not Completed 84 85
Reason Not Completed
Patient/guardian decision             32             41
Adverse Event             16             13
Physician Decision             14             11
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
Ongoing at interim data cutoff             1             1
Arm/Group Title OMB 20 mg TER 14 mg Total
Hide Arm/Group Description Ofatumumab 20 mg pre-filled syringes for subcutaneous injectionon on days 1 ,7 ,14, week 4 and every 4 weeks thereafter and a teriflunomide- matching placebo, taken orally once daily Teriflunomide 14 mg oral capsule taken once daily and matching placebo for subcutaneous injections to ofatumumab 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
[Not Specified]
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  
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)
Expanded disability status scale (EDSS)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Scores on a scale
Number Analyzed 481 participants 473 participants 954 participants
2.90  (1.343) 2.86  (1.374) 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 Gd-enhancing T1 lesions   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Number of 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) (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 pre-filled syringes for subcutaneous injectionon on days 1 ,7 ,14, week 4 and every 4 weeks thereafter and a teriflunomide- matching placebo, taken orally once daily
Teriflunomide 14 mg oral capsule taken once daily and matching placebo for subcutaneous injections to ofatumumab on days 1, 7, 14, week 4 and every 4 weeks thereafter
Overall Number of Participants Analyzed 469 469
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 0.415
Confidence Interval (2-Sided) 95%
0.308 to 0.559
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 is an increase from baseline in Expanded Disability Status Scale (EDSS) score sustained for at last 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 pre-filled syringes for subcutaneous injectionon on days 1 ,7 ,14, week 4 and every 4 weeks thereafter and a teriflunomide- matching placebo, taken orally once daily
Teriflunomide 14 mg oral capsule taken once daily and matching placebo for subcutaneous injections to ofatumumab on days 1, 7, 14, week 4 and every 4 weeks thereafter
Overall Number of Participants Analyzed 479 472
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 prespecified 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 0.036
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.660
Confidence Interval (2-Sided) 95%
0.447 to 0.974
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 pre-filled syringes for subcutaneous injectionon on days 1 ,7 ,14, week 4 and every 4 weeks thereafter and a teriflunomide- matching placebo, taken orally once daily
Teriflunomide 14 mg oral capsule taken once daily and matching placebo for subcutaneous injections to ofatumumab on days 1, 7, 14, week 4 and every 4 weeks thereafter
Overall Number of Participants Analyzed 479 472
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 prespecified 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 0.209
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.756
Confidence Interval (2-Sided) 95%
0.489 to 1.170
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 pre-filled syringes for subcutaneous injectionon on days 1 ,7 ,14, week 4 and every 4 weeks thereafter and a teriflunomide- matching placebo, taken orally once daily
Teriflunomide 14 mg oral capsule taken once daily and matching placebo for subcutaneous injections to ofatumumab on days 1, 7, 14, week 4 and every 4 weeks thereafter
Overall Number of Participants Analyzed 374 360
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 - 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 prespecified 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 0.094
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.516
Confidence Interval (2-Sided) 95%
0.932 to 2.466
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 pre-filled syringes for subcutaneous injectionon on days 1 ,7 ,14, week 4 and every 4 weeks thereafter and a teriflunomide- matching placebo, taken orally once daily
Teriflunomide 14 mg oral capsule taken once daily and matching placebo for subcutaneous injections to ofatumumab on days 1, 7, 14, week 4 and every 4 weeks thereafter
Overall Number of Participants Analyzed 439 434
Mean (95% Confidence Interval)
Unit of Measure: lesions per scan
0.0317
(0.021 to 0.048)
0.5141
(0.402 to 0.658)
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 0.062
Confidence Interval (2-Sided) 95%
0.037 to 0.101
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 pre-filled syringes for subcutaneous injectionon on days 1 ,7 ,14, week 4 and every 4 weeks thereafter and a teriflunomide- matching placebo, taken orally once daily
Teriflunomide 14 mg oral capsule taken once daily and matching placebo for subcutaneous injections to ofatumumab on days 1, 7, 14, week 4 and every 4 weeks thereafter
Overall Number of Participants Analyzed 448 443
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=448,431 Number Analyzed 448 participants 431 participants
0.64
(0.55 to 0.75)
4.15
(3.64 to 4.74)
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 0.89
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 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 0.74
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 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 0.76
Confidence Interval (2-Sided) 95%
0.71 to 0.81
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Neurofilament Light Chain (NfL) Concentration in Serum
Hide Description The NfL concentration (geometric mean concentration) will be 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, 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 pre-filled syringes for subcutaneous injectionon on days 1 ,7 ,14, week 4 and every 4 weeks thereafter and a teriflunomide- matching placebo, taken orally once daily
Teriflunomide 14 mg oral capsule taken once daily and matching placebo for subcutaneous injections to ofatumumab 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 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 pre-filled syringes for subcutaneous injectionon on days 1 ,7 ,14, week 4 and every 4 weeks thereafter and a teriflunomide- matching placebo, taken orally once daily
Teriflunomide 14 mg oral capsule taken once daily and matching placebo for subcutaneous injections to ofatumumab on days 1, 7, 14, week 4 and every 4 weeks thereafter
Overall Number of Participants Analyzed 437 434
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 0.129
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   0/481 (0.00%)   0/474 (0.00%) 
Hide Serious Adverse Events
OMB 20mg TER 14mg
Affected / at Risk (%) Affected / at Risk (%)
Total   38/481 (7.90%)   36/474 (7.59%) 
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%) 
Eye disorders     
Diplopia  1  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%) 
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%) 
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%) 
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%) 
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%) 
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%) 
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%) 
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%) 
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%) 
Renal and urinary disorders     
Urinary retention  1  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%) 
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%) 
Skin and subcutaneous tissue disorders     
Angioedema  1  1/481 (0.21%)  0/474 (0.00%) 
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%) 
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   339/481 (70.48%)   311/474 (65.61%) 
Gastrointestinal disorders     
Diarrhoea  1  28/481 (5.82%)  49/474 (10.34%) 
Nausea  1  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%) 
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%) 
Injury, poisoning and procedural complications     
Injection related reaction  1  119/481 (24.74%)  66/474 (13.92%) 
Investigations     
Blood immunoglobulin M decreased  1  30/481 (6.24%)  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%) 
Nervous system disorders     
Headache  1  68/481 (14.14%)  65/474 (13.71%) 
Psychiatric disorders     
Anxiety  1  28/481 (5.82%)  17/474 (3.59%) 
Depression  1  24/481 (4.99%)  24/474 (5.06%) 
Skin and subcutaneous tissue disorders     
Alopecia  1  27/481 (5.61%)  74/474 (15.61%) 
Vascular disorders     
Hypertension  1  20/481 (4.16%)  31/474 (6.54%) 
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 COMB157G2301
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: October 20, 2020