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Study to Evaluate Safety, Efficacy and Pharmacokinetics (PK) of a Modified Regimen of Ublituximab

Phase 3
Recruiting
Conditions
Relapsing Multiple Sclerosis
Interventions
Registration Number
NCT05877963
Lead Sponsor
TG Therapeutics, Inc.
Brief Summary

The primary purpose of this phase 3b study is to assess the efficacy of a modified regimen of ublituximab as measured by T1 Gadolinium (Gd)-enhancing lesions and pharmacokinetics in participants with Relapsing Multiple Sclerosis (RMS). The study consists of 2 parts: Part A is single-armed and open-label and Part B is randomized, double-blind, placebo-controlled.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
300
Inclusion Criteria
  • Diagnosis of RMS (2017 Revised McDonald criteria).

  • Participants must meet one of the following prior treatment definitions:

    1. Participants naïve to treatment.
    2. Participants previously treated with a disease modifying therapy (DMT) who have discontinued treatment prior to consent and meet the washout requirements.
  • Expanded Disability Status Scale (EDSS) score ≤ 5.5 at screening.

  • Neurologically stable for > 30 days prior to first dose of ublituximab.

  • Female participants of childbearing potential must consent to use a medically acceptable method of contraception from consent, throughout the study period, and for 6 months after the last dose of ublituximab.

Exclusion Criteria
  • History of any serious 3 Infusion Related Reaction (IRR) on prior anti-CD20 therapy.
  • Primary-progressive multiple sclerosis (PPMS) or inactive Secondary Progressive MS (SPMS).
  • Active chronic (or stable but treated with immune therapy) disease of the immune system other than MS (e.g., rheumatoid arthritis, scleroderma, Sjögren's syndrome, Crohn's disease, ulcerative colitis, etc.) or immunodeficiency syndrome (hereditary immune deficiency, drug-induced immune deficiency, etc.).
  • Current evidence or known history of clinically significant infection, including: chronic, recurrent, or ongoing active viral, bacterial, or fungal infectious disease requiring long term systemic treatment such as, but not limited to chronic urinary tract infection, chronic pulmonary infection with bronchiectasis, tuberculosis, or active hepatitis C virus (HCV).
  • Previous serious opportunistic or atypical infection.
  • Evidence of chronic active or history of hepatitis B virus (HBV) infection as evidenced by a detectable hepatitis B surface antigen (HBsAg), or positive hepatitis B core antibody (HBcAb), or chronic hepatitis C infection. Participants with positive hepatitis C virus antibody (HCV Ab) are eligible only if polymerase chain reaction (PCR) is negative for HCV ribonucleic acid (RNA).
  • History or evidence (clinical, radiological, or biomarker) of suspected or confirmed progressive multifocal leukoencephalopathy (PML).
  • Receipt of any live or live-attenuated vaccines (including vaccines for varicella-zoster virus or measles) within 4 weeks prior to first study drug administration.
  • Participants requiring treatment with intravenous immune globulin (IVIG) for decreased immunoglobulins within the 12 months prior to W1D1.
  • Any active malignancies other than adequately treated basal, squamous cell or in situ carcinoma.
  • Participants who have ever received ublituximab, alemtuzumab, cyclophosphamide, mitoxantrone, cladribine, or daclizumab (including for non-MS indications).

Note: Other Inclusion/Exclusion criteria may apply.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Part A: UblituximabUblituximabParticipants will receive a modified regimen of ublituximab including infusions on Day 1 of Week 1 (W1D1), Day 15, if applicable, and ublituximab 450 milligrams (mg) infusion at Week 24.
Part B: Ublituximab /Placebo (Treatment Arm A)UblituximabParticipants will receive 600 mg of ublituximab on W1D1 followed by a placebo infusion on Day 15 and 450 mg ublituximab infusion at Week 24.
Part B: Ublituximab /Placebo (Treatment Arm A)PlaceboParticipants will receive 600 mg of ublituximab on W1D1 followed by a placebo infusion on Day 15 and 450 mg ublituximab infusion at Week 24.
Part B: Ublituximab (Treatment Arm B)UblituximabParticipants will receive 150 mg of ublituximab on W1D1 followed by 450 mg on Day 15 and at Week 24.
Primary Outcome Measures
NameTimeMethod
Part A: Percentage of Participants With no Change or Reduction in Number of T1 Gd-Enhancing Lesions From Baseline to Week 48Baseline up to Week 48

The Gd-enhancing T1 lesions will be evaluated using magnetic resonance imaging (MRI) technique.

Part B: Area Under the Curve Over the First 16 Weeks (AUC0-W16) of UblituximabUp to Week 16
Secondary Outcome Measures
NameTimeMethod
Part A: Percentage of Participants Free of T1 Gd-Enhancing LesionsWeek 48

The Gd-enhancing T1 lesions will be evaluated using MRI technique.

Part A: Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM-9) ScoresBaseline, Week 24 and Week 48

The TSQM-9 is a 9-item questionnaire with 3 domains: Satisfaction, convenience, and effectiveness.

Part A and Part B: Percentage of Participants Experiencing Infusion Related Reactions (IRRs)Up to Week 48

IRRs are defined as infusion related adverse events (AEs) that occur within one day of an infusion and resolve within 7 days. IRRs will be reported by investigator.

Trial Locations

Locations (3)

TG Therapeutics Investigational Trial Site

🇺🇸

Milwaukee, Wisconsin, United States

TG Investigational Site

🇺🇸

Farmington, Michigan, United States

TG Therapeutics Investigational Trial SiteCharlotte

🇺🇸

Charlotte, North Carolina, United States

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