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

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ClinicalTrials.gov Identifier: NCT02738775
Recruitment Status : Completed
First Posted : April 14, 2016
Results First Posted : July 15, 2021
Last Update Posted : July 15, 2021
Sponsor:
Information provided by (Responsible Party):
TG Therapeutics, Inc.

Tracking Information
First Submitted Date  ICMJE April 10, 2016
First Posted Date  ICMJE April 14, 2016
Results First Submitted Date  ICMJE June 22, 2021
Results First Posted Date  ICMJE July 15, 2021
Last Update Posted Date July 15, 2021
Actual Study Start Date  ICMJE May 27, 2016
Actual Primary Completion Date September 27, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 22, 2021)
Responder Rate of B-Cell Depletion at Week 4 [ Time Frame: 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).
Original Primary Outcome Measures  ICMJE
 (submitted: April 11, 2016)
  • B-cell depletion [ Time Frame: Day 28 ]
    Measure B-cell depletion up to day 28
  • Determine Acceptable Adverse Events Related to Treatment [ Time Frame: 6 months on therapy ]
    To determine the incidence of adverse events and any abnormal laboratory values
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 22, 2021)
  • Number of New Gadolinium (Gd)-Enhancing T1 Lesions at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ]
    The Gd-enhancing T1 lesions were evaluated using magnetic resonance imaging (MRI) technique.
  • Number of New or Enlarging T2 Lesions at Weeks 24 and 48 [ Time Frame: Weeks 24 and 48 ]
    The new or enlarging T2 lesions were evaluated using MRI technique.
  • Annualized Relapse Rate (ARR) [ Time Frame: 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) [ Time Frame: Baseline to Week 48 ]
    RRR was calculated as the percentage reduction from baseline ARR to ARR at Week 48.
  • Percentage of Relapse Free Participants [ Time Frame: 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.
  • Change From Baseline in B Cells (CD19+), Memory (CD19+CD27+) and Naïve (CD19+CD27-[Negative]) B Cells [ Time Frame: 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 [ Time Frame: 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-CD4+ (Cluster of Differentiation 4 Positive) [ Time Frame: 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-CD8+ (Cluster of Differentiation 8 Positive) [ Time Frame: 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-Interleukin 10 (IL10) [ Time Frame: 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.
  • Additional Immune Profiling-Natural Killer (NK) Cells [ Time Frame: 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.
  • Pharmacokinetic Parameter: Plasma Concentration of Ublituximab [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: April 11, 2016)
Evaluate the % of relapses in relapsed multiple sclerosis patients [ Time Frame: up to 48 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase IIa Study of Ublituximab in Participants With Relapsing Forms of Multiple Sclerosis
Official Title  ICMJE 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.
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis
Intervention  ICMJE
  • Biological: Ublituximab
    Administered as an IV infusion.
    Other Name: TG-1101
  • Drug: Placebo
Study Arms  ICMJE
  • Experimental: Cohort 1
    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.
    Interventions:
    • Biological: Ublituximab
    • Drug: Placebo
  • Experimental: Cohort 2
    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.
    Interventions:
    • Biological: Ublituximab
    • Drug: Placebo
  • Experimental: Cohort 3
    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.
    Interventions:
    • Biological: Ublituximab
    • Drug: Placebo
  • Experimental: Cohort 4
    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.
    Interventions:
    • Biological: Ublituximab
    • Drug: Placebo
  • Experimental: Cohort 5
    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.
    Interventions:
    • Biological: Ublituximab
    • Drug: Placebo
  • Experimental: Cohort 6
    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.
    Interventions:
    • Biological: Ublituximab
    • Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 22, 2021)
49
Original Estimated Enrollment  ICMJE
 (submitted: April 11, 2016)
40
Actual Study Completion Date  ICMJE August 13, 2018
Actual Primary Completion Date September 27, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02738775
Other Study ID Numbers  ICMJE TG1101-RMS-201
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Plan Description: Data will be shared after study completion via publication
Responsible Party TG Therapeutics, Inc.
Study Sponsor  ICMJE TG Therapeutics, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Edward Fox, MD, PhD Central Texas Neurology
PRS Account TG Therapeutics, Inc.
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP