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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.

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

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Biological: Ublituximab Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 49 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: 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.
Actual Study Start Date : May 27, 2016
Actual Primary Completion Date : September 27, 2017
Actual Study Completion Date : August 13, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Biological: Ublituximab
Administered as an IV infusion.
Other Name: TG-1101

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.
Biological: Ublituximab
Administered as an IV infusion.
Other Name: TG-1101

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.
Biological: Ublituximab
Administered as an IV infusion.
Other Name: TG-1101

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.
Biological: Ublituximab
Administered as an IV infusion.
Other Name: TG-1101

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.
Biological: Ublituximab
Administered as an IV infusion.
Other Name: TG-1101

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.
Biological: Ublituximab
Administered as an IV infusion.
Other Name: TG-1101

Drug: Placebo



Primary Outcome Measures :
  1. 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).


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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).

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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+.

  9. 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+.

  10. 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.

  11. 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.

  12. 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.



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02738775


Locations
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United States, Arizona
TG Therapeutics Investigational Trial Site
Phoenix, Arizona, United States, 85018
United States, California
TG Therapeutics Investigational Trial Site
Pasadena, California, United States, 91105
TG Therapeutics Investigational Trial Site
Torrance, California, United States, 90502
United States, Colorado
TG Therapeutics Investigational Trial Site
Aurora, Colorado, United States, 80045
TG Therapeutics Investigational Trial Site
Fort Collins, Colorado, United States, 80528
United States, Kentucky
TG Therapeutics Investigational Trial Site
Lexington, Kentucky, United States, 40509
United States, New Jersey
TG Therapeutics Investigational Trial Site
Teaneck, New Jersey, United States, 07666
United States, Ohio
TG Therapeutics Investigational Trial Site
Akron, Ohio, United States, 44320
TG Therapeutics Investigational Trial Site
Columbus, Ohio, United States, 43201
United States, Tennessee
TG Therapeutics Investigational Trial Site
Knoxville, Tennessee, United States, 37922
United States, Texas
TG Therapeutics Investigational Trial Site
Round Rock, Texas, United States, 78681
TG Therapeutics Investigational Trial Site
San Antonio, Texas, United States, 78258
Sponsors and Collaborators
TG Therapeutics, Inc.
Investigators
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Study Chair: Edward Fox, MD, PhD Central Texas Neurology
  Study Documents (Full-Text)

Documents provided by TG Therapeutics, Inc.:
Study Protocol  [PDF] October 10, 2017
Statistical Analysis Plan  [PDF] February 3, 2021

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Responsible Party: TG Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT02738775    
Other Study ID Numbers: TG1101-RMS-201
First Posted: April 14, 2016    Key Record Dates
Results First Posted: July 15, 2021
Last Update Posted: July 15, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Data will be shared after study completion via publication
Keywords provided by TG Therapeutics, Inc.:
multiple sclerosis
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases