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

Primary Purpose

Multiple Sclerosis

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ublituximab
Placebo
Sponsored by
TG Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Sclerosis focused on measuring multiple sclerosis

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • TG Therapeutics Investigational Trial Site
  • TG Therapeutics Investigational Trial Site
  • TG Therapeutics Investigational Trial Site
  • TG Therapeutics Investigational Trial Site
  • TG Therapeutics Investigational Trial Site
  • TG Therapeutics Investigational Trial Site
  • TG Therapeutics Investigational Trial Site
  • TG Therapeutics Investigational Trial Site
  • TG Therapeutics Investigational Trial Site
  • TG Therapeutics Investigational Trial Site
  • TG Therapeutics Investigational Trial Site
  • TG Therapeutics Investigational Trial Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1

Cohort 2

Cohort 3

Cohort 4

Cohort 5

Cohort 6

Arm Description

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.

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.

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.
Number of New or Enlarging T2 Lesions at Weeks 24 and 48
The new or enlarging T2 lesions were evaluated using MRI technique.
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).
Relapse Rate Reduction (RRR)
RRR was calculated as the percentage reduction from baseline ARR to ARR at 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.
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.
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.
Additional Immune Profiling-CD4+ (Cluster of Differentiation 4 Positive)
A blood sample was collected and was sent to the laboratory for analysis of CD4+.
Additional Immune Profiling-CD8+ (Cluster of Differentiation 8 Positive)
A blood sample was collected and was sent to the laboratory for analysis of CD8+.
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.
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.
Pharmacokinetic Parameter: Plasma Concentration of Ublituximab
Plasma concentration is defined as the measured concentration of ublituximab.

Full Information

First Posted
April 10, 2016
Last Updated
June 22, 2021
Sponsor
TG Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02738775
Brief Title
Phase IIa Study of Ublituximab in Participants With Relapsing Forms of Multiple Sclerosis
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.
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
May 27, 2016 (Actual)
Primary Completion Date
September 27, 2017 (Actual)
Study Completion Date
August 13, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
TG Therapeutics, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
multiple sclerosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
49 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 5
Arm Type
Experimental
Arm Description
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.
Arm Title
Cohort 6
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Ublituximab
Other Intervention Name(s)
TG-1101
Intervention Description
Administered as an IV infusion.
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Responder Rate of B-Cell Depletion at Week 4
Description
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).
Time Frame
Week 4
Secondary Outcome Measure Information:
Title
Number of New Gadolinium (Gd)-Enhancing T1 Lesions at Weeks 24 and 48
Description
The Gd-enhancing T1 lesions were evaluated using magnetic resonance imaging (MRI) technique.
Time Frame
Weeks 24 and 48
Title
Number of New or Enlarging T2 Lesions at Weeks 24 and 48
Description
The new or enlarging T2 lesions were evaluated using MRI technique.
Time Frame
Weeks 24 and 48
Title
Annualized Relapse Rate (ARR)
Description
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).
Time Frame
Week 48
Title
Relapse Rate Reduction (RRR)
Description
RRR was calculated as the percentage reduction from baseline ARR to ARR at Week 48.
Time Frame
Baseline to Week 48
Title
Percentage of Relapse Free Participants
Description
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.
Time Frame
Week 48
Title
Change From Baseline in B Cells (CD19+), Memory (CD19+CD27+) and Naïve (CD19+CD27-[Negative]) B Cells
Description
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.
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
Title
Change From Baseline in Sustained B Cell
Description
Sustained B cell reduction is defined as B-cell reductions achieved on pre-dose at Week 24 and Week 48.
Time Frame
Baseline to pre-dose at Week 24 and Week 48
Title
Additional Immune Profiling-CD4+ (Cluster of Differentiation 4 Positive)
Description
A blood sample was collected and was sent to the laboratory for analysis of CD4+.
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
Title
Additional Immune Profiling-CD8+ (Cluster of Differentiation 8 Positive)
Description
A blood sample was collected and was sent to the laboratory for analysis of CD8+.
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
Title
Additional Immune Profiling-Interleukin 10 (IL10)
Description
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.
Time Frame
Baseline, Weeks 2, 4, 12, 20, 24, 25, 36, 44 and 48
Title
Additional Immune Profiling-Natural Killer (NK) Cells
Description
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.
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
Title
Pharmacokinetic Parameter: Plasma Concentration of Ublituximab
Description
Plasma concentration is defined as the measured concentration of ublituximab.
Time Frame
Day 1 (pre-dose); Week 2; Day 15 (pre-dose); Weeks 4, 24 (pre-dose) and 25

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Edward Fox, MD, PhD
Organizational Affiliation
Central Texas Neurology
Official's Role
Study Chair
Facility Information:
Facility Name
TG Therapeutics Investigational Trial Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85018
Country
United States
Facility Name
TG Therapeutics Investigational Trial Site
City
Pasadena
State/Province
California
ZIP/Postal Code
91105
Country
United States
Facility Name
TG Therapeutics Investigational Trial Site
City
Torrance
State/Province
California
ZIP/Postal Code
90502
Country
United States
Facility Name
TG Therapeutics Investigational Trial Site
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
TG Therapeutics Investigational Trial Site
City
Fort Collins
State/Province
Colorado
ZIP/Postal Code
80528
Country
United States
Facility Name
TG Therapeutics Investigational Trial Site
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40509
Country
United States
Facility Name
TG Therapeutics Investigational Trial Site
City
Teaneck
State/Province
New Jersey
ZIP/Postal Code
07666
Country
United States
Facility Name
TG Therapeutics Investigational Trial Site
City
Akron
State/Province
Ohio
ZIP/Postal Code
44320
Country
United States
Facility Name
TG Therapeutics Investigational Trial Site
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43201
Country
United States
Facility Name
TG Therapeutics Investigational Trial Site
City
Knoxville
State/Province
Tennessee
ZIP/Postal Code
37922
Country
United States
Facility Name
TG Therapeutics Investigational Trial Site
City
Round Rock
State/Province
Texas
ZIP/Postal Code
78681
Country
United States
Facility Name
TG Therapeutics Investigational Trial Site
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78258
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
Data will be shared after study completion via publication

Learn more about this trial

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

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