Multiple Sclerosis MedDRA version: 20.0 Level: PT Classification code 10029202 Term: Nervous system disorder System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
TG Therapeutics, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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 active treatment and the follow up period. 10. Fertile male subjects participating in the study who are sexually active with women of child bearing potential, must agree to use a condom during the treatment period and for an additional 20 weeks after cessation of active treatment. Agree to use an accelerated elimination procedure for teriflunomide or oral placebo after the last dose of study medications or early termination from the study. 11. Willingness and ability to comply with trial and follow-up procedures, give written consent. 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 440 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Treatment with Anti-CD20 or other B cell directed treatment 2.Treatment with the following therapies at any time prior to randomization: a.Alemtuzumab b.Natalizumab, c.Teriflunomide, d.Leflunomide e.Stem cell transplantation 3.Contraindications to teriflunomide or incompatibility with it's use 4.Therapies that are disallowed (min. of 4 weeks prior to randomization): phenytoin, warfarin, tolbutamide, St John’s Wort or cholestyramine 5.Prior DMT exposure within months of screening: a.24 months with cladribine b.6 months with daclizumab, azathioprine, methotrexate, or cyclophosphamide c.90 days with fingolimod, or experimental S1P modulators,, IV immunoglobulin, and plasmapheresis d.30 days with glatiramer acetate, interferons, dimethyl fumarate, or glucocorticoids 6.Diagnosed with Primary Progressive MS (PPMS) 7.Pregnant or nursing 8.= 10 years disease duration from onset with subjects EDSS = 2.0 9.Contraindication for MRI and/or gadolinium 10.Known presence of other neurologic disorders that may mimic MS 11.Current evidence or known history of clinically significant infection including: a.Chronic or ongoing active viral, bacterial, or fungal infectious disease requiring long term systemic treatment such as, but not limited to: PML, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, or active hepatitis C b.Previous serious opportunistic or atypical infections c.History of positive serology for hepatitis B or hepatitis C or HIV 12. History of clinically significant CNS trauma (e.g. traumatic brain injury, cerebral contusion, spinal cord compression) 13.History of liver disease, including but not limited to: a.Known history of active hepatitis B or C any time prior to randomization or known history of active hepatitis A within 3 years prior to randomization b.Presence of chronic liver or biliary disease c.Moderate or severe hepatic impairment defined as Child Pugh Score B or C, respectively, based on measurement of total bilirubin, serum albumin, International Normalized Ratio (INR) and as well as on presence /absence and severity of ascites and hepatic encephalopathy d.Any of the following abnormal laboratory values at screening or first infusion: •ALT/SGPT>2X the Upper Limit of Normal (ULN) •AST/SGOT>2X ULN 14.Previous diagnosis with a congenital or acquired immunodeficiency 15.History of renal impairment, including, but not limited to: a.Hypoproteinemia (e.g., in case of severe liver disease or nephrotic syndrome) with serum albumin <3.0 g/dL b.Severe renal insufficiency requiring renal dialysis 16.Past or current history of medically significant adverse effects (including allergic reactions) from: a.Corticosteroids b.Diphenhydramine c.Murine or mouse/human chimeric antibodies 17.Subjects with significantly impaired bone marrow function or significant anemia, leukopenia, or thrombocytopenia a.Hematocrit <24% and/or b.Absolute white blood cell count <4,000 cells/mm3 and/or c.Platelet count <150,000 cells/mm3 and/or d.Absolute neutrophil = 1,500 cells/mm3 18.Absolute neutrophil count or platelet count outside of normal range (as per reference laboratory) 19.Absolute lymphocyte counts less than 1000/microliter 20.Any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: a.Symptomatic, or history of documented congestive heart failure (New York Heart Association functional cl
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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.;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. ;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.;Timepoint(s) of evaluation of this end point: 96 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 | — |
Countries
Belarus, Georgia, Poland, Russian Federation, Serbia, Spain, Ukraine, United Kingdom, United States
Contacts
Public ContactGyorgy Andor
PSI CRO Hungary LLC
Outcome results
None listed