Phase IIa Study of Ublituximab in Participants With Relapsing Forms of Multiple Sclerosis
- Conditions
- Multiple Sclerosis
- Interventions
- Biological: UblituximabDrug: Placebo
- Registration Number
- NCT02738775
- Lead Sponsor
- TG Therapeutics, Inc.
- Brief Summary
This study evaluates the use of single agent ublituximab, a novel monoclonal antibody, in participants with relapsing forms of multiple sclerosis.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 49
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Cohort 3 Placebo 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. Cohort 4 Placebo 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. Cohort 5 Ublituximab 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. Cohort 3 Ublituximab 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. Cohort 6 Placebo 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. Cohort 1 Ublituximab 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. Cohort 2 Ublituximab 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. Cohort 2 Placebo 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. Cohort 4 Ublituximab 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. Cohort 6 Ublituximab 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. Cohort 1 Placebo 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. Cohort 5 Placebo 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.
- Primary Outcome Measures
Name Time Method Responder Rate of B-Cell Depletion at Week 4 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).
- Secondary Outcome Measures
Name Time Method Percentage of Relapse Free Participants Week 48 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.
Number of New Gadolinium (Gd)-Enhancing T1 Lesions at Weeks 24 and 48 Weeks 24 and 48 The Gd-enhancing T1 lesions were evaluated using magnetic resonance imaging (MRI) technique.
Change From Baseline in B Cells (CD19+), Memory (CD19+CD27+) and Naïve (CD19+CD27-[Negative]) B Cells 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 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.
Change From Baseline in Sustained B Cell Baseline to pre-dose at Week 24 and Week 48 Sustained B cell reduction is defined as B-cell reductions achieved on pre-dose at Week 24 and Week 48.
Additional Immune Profiling-Natural Killer (NK) Cells 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 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.
Number of New or Enlarging T2 Lesions at Weeks 24 and 48 Weeks 24 and 48 The new or enlarging T2 lesions were evaluated using MRI technique.
Annualized Relapse Rate (ARR) Week 48 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).
Relapse Rate Reduction (RRR) Baseline to Week 48 RRR was calculated as the percentage reduction from baseline ARR to ARR at Week 48.
Additional Immune Profiling-CD8+ (Cluster of Differentiation 8 Positive) 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 A blood sample was collected and was sent to the laboratory for analysis of CD8+.
Additional Immune Profiling-CD4+ (Cluster of Differentiation 4 Positive) 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 A blood sample was collected and was sent to the laboratory for analysis of CD4+.
Additional Immune Profiling-Interleukin 10 (IL10) Baseline, Weeks 2, 4, 12, 20, 24, 25, 36, 44 and 48 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.
Pharmacokinetic Parameter: Plasma Concentration of Ublituximab Day 1 (pre-dose); Week 2; Day 15 (pre-dose); Weeks 4, 24 (pre-dose) and 25 Plasma concentration is defined as the measured concentration of ublituximab.
Trial Locations
- Locations (1)
TG Therapeutics Investigational Trial Site
🇺🇸San Antonio, Texas, United States