Clinical trial NCT05877963: Study to Evaluate Safety, Efficacy and Pharmacokinetics (PK) of a Modified Regimen of Ublituximab
Official title: Evaluating Safety, Efficacy and Pharmacokinetics of a Modified Regimen of Ublituximab (ENHANCE )
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Relapsing Multiple Sclerosis
Lead sponsor: TG Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2023-05-26
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Part A: Percentage of Participants With no Change or Reduction in Number of T1 Gd-Enhancing Lesions From Baseline to Week 48
timeFrame: Baseline up to Week 48
measure: Part B: Area Under the Curve Over the First 16 Weeks (AUC0-W16) of Ublituximab
timeFrame: Up to Week 16
Secondary outcomes:
measure: Part A and Part B: Percentage of Participants Experiencing Infusion Related Reactions (IRRs)
timeFrame: Up to Week 48
measure: Part A: Percentage of Participants Free of T1 Gd-Enhancing Lesions
timeFrame: Week 48
measure: Part A: Change From Baseline in Treatment Satisfaction Questionnaire for Medication (TSQM-9) Scores
timeFrame: Baseline, Week 24 and Week 48
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Alabama
city: Cullman
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Alabama
city: Orange
country: United States
facility: TG Therapeutics Investigational Trial Site
state: California
city: Fort Collins
country: United States
facility: TG Investigational Site
state: Colorado
city: Washington
country: United States
facility: TG Therapeutics Investigational Trial Site
state: District of Columbia
city: Tampa
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Florida
city: Chicago
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Illinois
city: Indianapolis
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Indiana
city: Iowa City
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Iowa
city: Overland Park
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Kansas
city: Lutherville
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Maryland
city: Boston
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Massachusetts
city: Foxboro
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Massachusetts
city: North Worcester
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Massachusetts
city: Farmington
country: United States
facility: TG Investigational Site
state: Michigan
city: Golden Valley
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Minnesota
city: Plymouth
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Minnesota
city: Saint Louis
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Missouri
city: New York
country: United States
facility: TG Therapeutics Investigational Trial Site
state: New York
city: New York
country: United States
facility: TG Therapeutics Investigational Trial Site
state: New York
city: Charlotte
country: United States
facility: TG Therapeutics Investigational Trial SiteCharlotte
state: North Carolina
city: Raleigh
country: United States
facility: TG Therapeutics Investigational Trial Site
state: North Carolina
city: Cleveland
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Ohio
city: Dayton
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Ohio
city: Oklahoma City
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Oklahoma
city: Greenville
country: United States
facility: TG Therapeutics Investigational Trial Site
state: South Carolina
city: Knoxville
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Tennessee
city: Waco
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Texas
city: Salt Lake City
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Utah
city: Vienna
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Virginia
city: Kirkland
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Washington
city: Seattle
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Washington
city: Spokane
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Washington
city: Milwaukee
country: United States
facility: TG Therapeutics Investigational Trial Site
state: Wisconsin
Study officials:
References: