A Study of Orelabrutinib in Patients With Secondary Progressive Multiple Sclerosis

Last updated: June 3, 2026
Sponsor: Zenas BioPharma (USA), LLC
Overall Status: Active - Recruiting

Phase

3

Condition

Multiple Sclerosis

Treatment

Orelabrutinib

Placebo

Clinical Study ID

NCT07299019
ZB020-03-002
  • Ages 18-60
  • All Genders

Study Summary

Orelabrutinib is a CNS-penetrable BTK inhibitor. This is a phase 3, randomized, double-blind, parallel-group, multicenter study to evaluate the efficacy and safety of orelabrutinib compared with placebo in patients with non-active Secondary Progress MS. Patients will be treated for approximately 24 to 60 months, with a minimum treatment duration of 12 months. The study will enroll approximately 990 subjects in a 2:1 randomization (orelabrutinib: placebo), globally.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. 18 to 60 years of age, inclusive, at the time of signing the informed consent.

  2. Participant must have a previous diagnosis of RRMS in accordance with 2024 McDonaldcriteria

  3. Participant must have a current diagnosis of SPMS in accordance with the clinicalcourse criteria revised in 2013

  4. Participant must have documented evidence of disability progression independent ofclinical relapse observed during the 24 months before screening. A written summaryof the clinical evidence of disability progression must be discussed and alignedbetween the Investigator and the Sponsor's dedicated qualified person(s).

  5. Absence of clinical relapses for at least 24 months.

Exclusion

Exclusion Criteria:

  1. The patient has been diagnosed with primary progressive MS (PPMS) according to 2024McDonald diagnostic criteria

  2. Immunologic disorder other than MS or any other conditions requiring corticosteroidtherapy.

  3. History or current diagnosis of other neurological disorders that may mimic MS

  4. History or current diagnosis of progressive multifocal leukoencephalopathy

  5. Active, clinically significant viral, bacterial, or fungal infection

  6. History of any other significant active medical condition

  7. History of suicidal behavior within 6 months prior to Screening

  8. Any prior history of malignancy

  9. Patients on anticoagulation, or antiplatelet therapy

  10. Patients took strong/moderate CYP3A inhibitors or strong/moderate CYP3A inducerswithin 14 days

  11. Clinically significant laboratory abnormalities at Screening.

  12. Vaccination with live or live-attenuated virus vaccine within 1 month prior toScreening

  13. History of alcohol abuse or alcohol use disorder or other drug abuse within 12months prior to screening.

Study Design

Total Participants: 990
Treatment Group(s): 2
Primary Treatment: Orelabrutinib
Phase: 3
Study Start date:
March 23, 2026
Estimated Completion Date:
July 31, 2030

Study Description

This is a phase 3, randomized, double-blind, parallel-group, multicenter study to evaluate the efficacy and safety of orelabrutinib compared with placebo in patients with naSPMS. The study will enroll approximately 990 subjects in a 2:1 randomization (orelabrutinib: placebo), globally.

The study consists of the following periods:

  • Screening Period: Up to 4 weeks.

  • Treatment Period: The duration of treatment will vary for individual participants ranging from approximately 24 to 60 months, depending on the time of recruitment. A month is defined as a period of 28 days by convention.

  • Double-blinded (DB) Treatment: All eligible participants will be randomized at 2:1 ratio to accept orelabrutinib QD or placebo during the DB treatment period. The study will be unblinded when all participants in the DB period have reached a minimum treatment duration of 12 months at the time of primary analysis timing cutoff.

  • Open-label (OL) Treatment: Participants with 24-week CDP as assessed by EDSS are eligible for 2-year open-label orelabrutinib treatment.

  • Safety Follow-Up Period: It will last 4 weeks. The safety follow-up period will begin when the participants discontinue from the treatment before the end of the trial for any reasons or complete the trial but do not enter the long-term safety study (LTS) (see below).

All active study participants will have a final end of study (EOS) visit within 4 weeks of the study end date. Participants who are receiving IMP in DB or OL but do not consent to or are not eligible for enrollment in the LTS study, must return for a final safety follow-up visit 4 weeks later. For participants who intend and are eligible to join the LTS, open-label treatment with orelabrutinib will continue and no safety follow-up will occur.

Connect with a study center

  • Arizona Neuroscience Research, LLC

    Phoenix, Arizona 85032
    United States

    Active - Recruiting

  • Perseverance Research Center, LLC (PRC)

    Scottsdale, Arizona 85253
    United States

    Active - Recruiting

  • Fullerton Neurology and Headache Center

    Fullerton, California 92835
    United States

    Active - Recruiting

  • Regina Berkovich MD, PhD Inc

    West Hollywood, California 90048
    United States

    Active - Recruiting

  • Nova Clinical Research, LLC

    Bradenton, Florida 34209
    United States

    Active - Recruiting

  • Neurology Associates

    Maitland, Florida 32751
    United States

    Active - Recruiting

  • KC Research Center, PA Neurology Research Dept

    Roeland Park, Kansas 66205
    United States

    Active - Recruiting

  • Boston Clinical Trials

    Boston, Massachusetts 02131
    United States

    Site Not Available

  • Profound Research LLC at Oakland Neurology Center

    Rochester Hills, Michigan 48307
    United States

    Active - Recruiting

  • Washington University School of Medicine

    St Louis, Missouri 63110
    United States

    Active - Recruiting

  • Lone Star Neurology

    San Antonio, Texas 78258
    United States

    Active - Recruiting

  • Texas Institute for Neurological Disorders - Sherman

    Sherman, Texas 75092
    United States

    Active - Recruiting

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