Phase III: UbLiTuximab In Multiple Sclerosis Treatment Effects (ULTIMATE I STUDY)

INTERVENTION: Product Name: Ublituximab Product Code: TG‐1101 Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: UBLITUXIMAB Current Sponsor code: TGTX 1101 Other descriptive name: LFB‐R603 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 25‐ Pharmaceutical form of the placebo: Solution for infusion Route of administration of the placebo: Intravenous use Product Name: Teriflunomide Pharmaceutical Form: Film‐coated tablet 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: Film‐coated tablet Route of administration of the placebo: Oral use CONDITION: Multiple Sclerosis ; MedDRA version: 20.0 Level: PT Classification code 10029202 Term: Nervous system disorder System Organ Class: 10029205 ‐ Nervous system disorders Therapeutic area: Diseases [C] ‐ Nervous System Diseases [C10] PRIMARY OUTCOME: Main Objective: To determine the annualized relapse rate (ARR) in subjects with RMS after 96 weeks (approximately 2 years) treatment with IV infusion of ublituximab/oral placebo compared to 14 mg oral teriflunomide/IV placebo. Primary end point(s): The primary efficacy endpoint is ARR defined as the number of confirmed relapsed per‐subject year. The estimate of ARR for a treatment group will be the total number of relapsed for subjects in the respective treatment group divided by the sum of duration on study for subjects in that specific treatment group. Secondary Objective: The secondary objectives are to examine the effects of ublituximab/oral placebo as compared to teriflunomide/IV placebo as follows:; 1.On MRI parameters,; 2.The percentage with accumulation of disability, ; 3.Time to onset of confirmed disability progression for at least 12 weeks,; 4.The percentage of subject with a relapse, ; 5.Time to first confirmed relapse,; 6.The percentage of subjects with no evidence of disease activity (NEDA), and ; 7.To evaluate the safety of ublituximab/oral placebo, as determined by adverse events (AEs) and serious adverse event (SAEs), including MS worsening. ; Timepoint(s) of evaluation of this end point: 96 weeks SECONDARY OUTCOME: Secondary end point(s): Key secondary efficacy endpoints are as follows: ; 1.MRI parameters, ; a.The total number of gadolinium enhancing (Gd‐enhancing) T1‐lesions per MRI scan over the treatment period ; b.Volume of hypointense post‐gadolinium T1 lesion component (black holes) ; c.Volume of T2 lesion ; d.Brain volume changes ; 2.The percent of subjects with no evidence of disease activity (NEDA) ; a.NEDA is defined as subjects without relapses, MRI activities (no T1 Gd+ lesions and no new/enlarging T2 lesions), and no 12‐week confirmed disability progression. ; 3.The percentage of subjects with accumulation of disability ; a.Time to onset of confirmed disability progression for at least 12 weeks ; b.Percent of subjects free of disability progression at 6 months, 1 year, and 2 years ; 4.The percentage of subjects with a relapse ; 5.Time to first confirmed relapse Timepoint(s) of evaluation of this end point: Week 12, 24, 48, 72, 96 INCLUSION CRITERIA: 1. 18‐55 age 2. Diagnosis of RMS (McDonald criteria 2010) 3. = 2 relapses in prior 2 years or 1 relapse in the year prior to screening and/or =1 Gd enhancing lesion 4. Documented MRI of brain with abnormalities consistent with MS 5. Active disease 6. EDSS 0‐5.5 (inclusive) at screening 7. B cell counts =5% of total lymphocytes 8. Neurologic stability = 30 days prior to screening and baseline 9. Female subjects who are not of child‐bearing potential, have documented surgical sterilization ,and female subjects of child‐bearing potential who have a negative serum pregnancy test at baseline. Female subjects of child‐bearing potential, and all male partners must consent to use a medically/clinically acceptable method of contraception throughout the treatment period and for 20 weeks after the cessation of active treatment. Female subjects of child‐bearing potential must agree to undertake urine pregnancy tests every 4 weeks during act