A randomized, double-blind, double-dummy, parallel-group study comparing the efficacy and safety of ofatumumab versus teriflunomide in patients with relapsing multiple sclerosis

INTERVENTION:

Trade Name: Arzerra Product Name: ofatumumab Product Code: OMB157G Pharmaceutical Form: Solution for injection in pre‐filled syringe INN or Proposed

INN:

OFATUMUMAB CAS Number: 679818‐59‐8 Current Sponsor code: OMB157 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 50‐ Pharmaceutical form of the placebo: Solution for injection in pre‐filled syringe Route of administration of the placebo: Subcutaneous use Trade Name: Aubagio Product Name: Teriflunomide Pharmaceutical Form: Capsule, hard INN or Proposed

INN:

TERIFLUNOMIDE CAS Number: 108605‐62‐5 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 14‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use

CONDITION:

multiple sclerosis ; MedDRA version: 20.0 Level: PT Classification code 10048393 Term: Multiple sclerosis relapse System Organ Class: 10029205 ‐ Nervous system disorders Therapeutic area: Diseases [C] ‐ Nervous System Diseases [C10]

PRIMARY OUTCOME:

Main Objective: Demonstrate that ofatumumab 20 mg sc once every 4 (q4) weeks is superior to teriflunomide 14 mg po once daily in reducing the frequency of confirmed relapses as evaluated by the annualized relapse rate (ARR) in patients with relapsing MS. Primary end point(s): Demonstrate that ofatumumab 20 mg sc once every 4 (q4) weeks is superior to teriflunomide 14 mg po once daily in reducing the frequency of confirmed relapses as evaluated by the annualized relapse rate (ARR) in patients with relapsing MS. Secondary Objective: Key secondary objectives; ; To evaluate if ofatumumab is superior to teriflunomide on:; 1. Time to disability worsening as measured by 3‐month confirmed worsening (3mCDW) on EDSS ; 2. Number of T1 GdE lesions per MRI scan ; 3. Number of new or enlarging T2 lesions on MRI per year (annualized T2 lesion rate); 4. Time to disability worsening as measured by 6‐month confirmed worsening (6mCDW) on EDSS; 5. Rate of brain volume loss (BVL) based on assessments of percentage brain volume change from baseline; 6. Time to disability improvement, as measured by 6‐month confirmed improvement (6mCDI) on EDSS; 7. Neurofilament light chain (NfL) concentration in serum ; ; See protocol for complete list of secondary objectives. Timepoint(s) of evaluation of this end point: Up to 30 months

SECONDARY OUTCOME:

Secondary end point(s): ‐Time to disability worsening as measured by 3‐month confirmed worsening (3mCDW) on The Expanded Disability Status Scale (EDSS). ; ‐Time to disability worsening as measured by 6‐month confirmed worsening (6mCDW) on EDSS. ; ‐Time to disability improvement as measured by 6‐month confirmed improvement (6mCDI) on EDSS. ; ‐Number of T1 Gd‐enhancing lesions per MRI scan. ; ‐Number of new or enlarging T2 lesions on MRI per year (annualized T2 lesion rate). ; ‐Rate of brain volume loss (BVL) based on assessments of percentage brain volume change from baseline. ; ‐Neurofilament light chain (NfL) concentration in serum Timepoint(s) of evaluation of this end point: Up to 30 months

INCLUSION CRITERIA:

•Male or female patients aged 18 to 55 years (inclusive) at screening •Diagnosis of MS according to the 2010 Revised McDonald criteria •Relapsing form of MS.: relapsing‐remitting course (RRMS), or secondary progressive course with disease activity (relapsing SPMS) •Disability status at Screening with an EDSS score of 0 to 5.5 (inclusive) •Neurologically stable within 1 month prior to randomization •At least 1 documented relapse during the previous 1 year OR at least 2 documented relapses during the previous 2 years OR a positive GdE MRI scan during the year prior to randomization and including screening. Please see protocol for complete detailed list of inclusion criteria Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 900 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range