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

June 22, 2021 updated by: TG Therapeutics, Inc.

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.

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

49

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85018
        • TG Therapeutics Investigational Trial Site
    • California
      • Pasadena, California, United States, 91105
        • TG Therapeutics Investigational Trial Site
      • Torrance, California, United States, 90502
        • TG Therapeutics Investigational Trial Site
    • Colorado
      • Aurora, Colorado, United States, 80045
        • TG Therapeutics Investigational Trial Site
      • Fort Collins, Colorado, United States, 80528
        • TG Therapeutics Investigational Trial Site
    • Kentucky
      • Lexington, Kentucky, United States, 40509
        • TG Therapeutics Investigational Trial Site
    • New Jersey
      • Teaneck, New Jersey, United States, 07666
        • TG Therapeutics Investigational Trial Site
    • Ohio
      • Akron, Ohio, United States, 44320
        • TG Therapeutics Investigational Trial Site
      • Columbus, Ohio, United States, 43201
        • TG Therapeutics Investigational Trial Site
    • Tennessee
      • Knoxville, Tennessee, United States, 37922
        • TG Therapeutics Investigational Trial Site
    • Texas
      • Round Rock, Texas, United States, 78681
        • TG Therapeutics Investigational Trial Site
      • San Antonio, Texas, United States, 78258
        • TG Therapeutics Investigational Trial Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 53 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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.
Drug: Placebo
Biological: Ublituximab
Administered as an IV infusion.
Other Names:
  • TG-1101
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.
Drug: Placebo
Biological: Ublituximab
Administered as an IV infusion.
Other Names:
  • TG-1101
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.
Drug: Placebo
Biological: Ublituximab
Administered as an IV infusion.
Other Names:
  • TG-1101
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.
Drug: Placebo
Biological: Ublituximab
Administered as an IV infusion.
Other Names:
  • TG-1101
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.
Drug: Placebo
Biological: Ublituximab
Administered as an IV infusion.
Other Names:
  • TG-1101
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.
Drug: Placebo
Biological: Ublituximab
Administered as an IV infusion.
Other Names:
  • TG-1101

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Week 4

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
Week 48
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.
Weeks 24 and 48
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.
Weeks 24 and 48
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.
Baseline to 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.
Week 48
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.
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
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.
Baseline to 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+.
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)
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+.
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)
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.
Baseline, Weeks 2, 4, 12, 20, 24, 25, 36, 44 and 48
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.
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
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.
Day 1 (pre-dose); Week 2; Day 15 (pre-dose); Weeks 4, 24 (pre-dose) and 25

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

TG Therapeutics, Inc.

Investigators

  • Study Chair: Edward Fox, MD, PhD, Central Texas Neurology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 27, 2016

Primary Completion (Actual)

September 27, 2017

Study Completion (Actual)

August 13, 2018

Study Registration Dates

First Submitted

April 10, 2016

First Submitted That Met QC Criteria

April 11, 2016

First Posted (Estimate)

April 14, 2016

Study Record Updates

Last Update Posted (Actual)

July 15, 2021

Last Update Submitted That Met QC Criteria

June 22, 2021

Last Verified

June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TG1101-RMS-201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

IPD Plan Description

Data will be shared after study completion via publication

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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