Phase IIa Study of Ublituximab in Participants With Relapsing Forms of Multiple Sclerosis

Study Overview
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Brief Summary
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This study evaluates the use of single agent ublituximab, a novel monoclonal antibody, in participants with relapsing forms of multiple sclerosis.

Official Title
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A Placebo-Controlled Multi-Center Phase IIa Dose Finding Study of Ublituximab, a Third-Generation Anti-CD20 Monoclonal Antibody, in Patients With Relapsing Forms of Multiple Sclerosis.

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Biological: Ublituximab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of relapsing multiple sclerosis Active disease Greater than or equal to (≥) 2 relapses in prior 2 years or 1 relapse in the year prior to screening and/or ≥1 gadolinium (Gd) enhancing lesion Exclusion Criteria: Treatment with anti-cluster of differentiation 20 (CD20) monoclonal antibody within the last 12 months Treatment with alemtuzumab within the last 12 months Pregnant or nursing mothers

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Participant received intravenous (IV) infusion of ublituximab 150 milligrams (mg)/4 hour (hr) on Day 1, 450 mg/3 hr on Day 15 and 450 mg/1.5 hr on Week 24. Some participants initially received placebo IV infusion /4 hr on Day 1 and /3 hr on Day 15 before receiving ublituximab. | Biological: Ublituximab<br>* Administered as an IV infusion.<br>* Other names: TG-1101;Drug: Placebo<br> <br> |
| Experimental: Cohort 2<br>Participant received IV infusion of ublituximab 150 mg/4 hr on Day 1, 450 mg/1.5 hr on Day 15 and 450 mg/1 hr on Week 24. Some participants initially received placebo IV infusion /4 hr on Day 1 and /1.5 hr on Day 15 before receiving ublituximab. | Biological: Ublituximab<br>* Administered as an IV infusion.<br>* Other names: TG-1101;Drug: Placebo<br> <br> |
| Experimental: Cohort 3<br>Participant received IV infusion of ublituximab 150 mg/4 hr on Day 1, 450 mg/1 hr on Day 15 and 600 mg/1 hr on Week 24. Some participants initially received placebo IV infusion /4 hr on Day 1 and /1 hr on Day 15 before receiving ublituximab. | Biological: Ublituximab<br>* Administered as an IV infusion.<br>* Other names: TG-1101;Drug: Placebo<br> <br> |
| Experimental: Cohort 4<br>Participant received IV infusion of ublituximab 150 mg/3 hr on Day 1, 600 mg/1 hr on Day 15 and 600 mg/1 hr on Week 24. Some participants initially received placebo IV infusion /3 hr on Day 1 and /1 hr on Day 15 before receiving ublituximab. | Biological: Ublituximab<br>* Administered as an IV infusion.<br>* Other names: TG-1101;Drug: Placebo<br> <br> |
| Experimental: Cohort 5<br>Participant received IV infusion of ublituximab 150 mg/2 hr on Day 1, 600 mg/1 hr on Day 15 and 600 mg/1 hr on Week 24. Some participants initially received placebo IV infusion /2 hr on Day 1 and /1 hr on Day 15 before receiving ublituximab. | Biological: Ublituximab<br>* Administered as an IV infusion.<br>* Other names: TG-1101;Drug: Placebo<br> <br> |
| Experimental: Cohort 6<br>Participant received IV infusion of ublituximab 150 mg/1 hr on Day 1, 600 mg/1 hr on Day 15 and 600 mg/1 hr on Week 24. Some participants initially received placebo IV infusion /1 hr on Day 1 and /1 hr on Day 15 before receiving ublituximab. | Biological: Ublituximab<br>* Administered as an IV infusion.<br>* Other names: TG-1101;Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder Rate of B-Cell Depletion at Week 4 | Responders Rate is defined as percentage of participants with greater than or equal to (≥) 95% reduction of B cells (cluster of differentiation 19 positive [CD19+] cells) within 2 weeks after the second infusion (Day 15). | Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of New Gadolinium (Gd)-Enhancing T1 Lesions at Weeks 24 and 48 | The Gd-enhancing T1 lesions were evaluated using magnetic resonance imaging (MRI) technique. | Weeks 24 and 48 | 
| Number of New or Enlarging T2 Lesions at Weeks 24 and 48 | The new or enlarging T2 lesions were evaluated using MRI technique. | Weeks 24 and 48 | 
| Annualized Relapse Rate (ARR) | ARR at Week 48 is calculated as the ratio of the sum of all participants confirmed relapse counts divided by the sum of all participants treatment duration (in years). | Week 48 | 
| Relapse Rate Reduction (RRR) | RRR was calculated as the percentage reduction from baseline ARR to ARR at Week 48. | Baseline to Week 48 | 
| Percentage of Relapse Free Participants | Participant was considered as free of clinical relapse if participant had no confirmed clinical relapse before treatment discontinuation/until end of Week 48. Relapses are defined as the occurrence of new or worsening neurological symptoms attributable to multiple sclerosis (MS), and immediately preceded by a stable or improving neurological state of at least 30 days. | Week 48 | 
| Change From Baseline in B Cells (CD19+), Memory (CD19+CD27+) and Naïve (CD19+CD27-[Negative]) B Cells | Cluster of Differentiation (CD)19 is a marker of B cells, the protein has been used to diagnose cancers that arise from this type of cell - notably B cell lymphomas, acute lymphoblastic leukemia (ALL), and chronic lymphocytic leukemia (CLL). The majority of B cell malignancies express normal to high levels of CD19. Memory B cell is a type of B lymphocyte that forms part of the adaptive immune system. These cells develop within germinal centers of the secondary lymphoid organs. Their function is to memorize the characteristics of the antigen that activated their parent B cell during initial infection such that if the memory B cell later encounters the same antigen, it triggers an accelerated and robust secondary immune response. A naive B cell is a B cell that has not been exposed to an antigen. Once exposed to an antigen, the naive B cell either becomes a memory B cell or a plasma cell that secretes antibodies specific to the antigen that was originally bound. | Baseline, Week 1 Day 2, Week 2, Week 3 Day 15, Weeks 4, 8, 12, 16, 20, 24, Week 24 plus 2 days, Weeks 25, 28, 36, 40, 44 and 48 | 
| Change From Baseline in Sustained B Cell | Sustained B cell reduction is defined as B-cell reductions achieved on pre-dose at Week 24 and Week 48. | Baseline to pre-dose at Week 24 and Week 48 | 
| Additional Immune Profiling-CD4+ (Cluster of Differentiation 4 Positive) | A blood sample was collected and was sent to the laboratory for analysis of CD4+. | Baseline, Week 1 Day 2, Week 2, Week 3 Day 15, Weeks 4, 8, 12, 16, 20, 24, Week 24 Plus 2 Days, Weeks 25, 28, 36, 40, 44 and 48 | 
| Additional Immune Profiling-CD8+ (Cluster of Differentiation 8 Positive) | A blood sample was collected and was sent to the laboratory for analysis of CD8+. | Baseline, Week 1 Day 2, Week 2, Week 3 Day 15, Weeks 4, 8, 12, 16, 20, 24, Week 24 Plus 2 Days, Weeks 25, 28, 36, 40, 44 and 48 | 
| Additional Immune Profiling-Interleukin 10 (IL10) | A blood sample was collected and was sent to the laboratory for analysis of IL-10. IL-10 is an anti-inflammatory cytokine that maintains the balance of the immune response, allowing the clearance of infection while minimizing damage to the host. | Baseline, Weeks 2, 4, 12, 20, 24, 25, 36, 44 and 48 | 
| Additional Immune Profiling-Natural Killer (NK) Cells | A blood sample was collected and was sent to the laboratory for analysis of NK cells. Percentage of NK cells per ml of blood. NK cells are lymphocytes with the ability to kill tumor cells without deliberate immunization or activation. | Baseline, Week 1 Day 2, Week 2, Week 3 Day 15, Weeks 4, 8, 12, 16, 20, 24, Week 24 Plus 2 Days, Weeks 25, 28, 36, 40, 44 and 48 | 
| Pharmacokinetic Parameter: Plasma Concentration of Ublituximab | Plasma concentration is defined as the measured concentration of ublituximab. | Day 1 (pre-dose); Week 2; Day 15 (pre-dose); Weeks 4, 24 (pre-dose) and 25 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiple sclerosis