Orelabrutinib treatment for primary progressive multiple sclerosis

A Phase 3, Randomized, Double-blind, Efficacy and Safety Study Comparing Orelabrutinib to Placebo in Patients With Primary Progressive Multiple Sclerosis

PHASE3 · Zenas BioPharma (USA), LLC · NCT07067463

This trial tests whether orelabrutinib, a brain-penetrant BTK inhibitor, can slow disability progression in adults with primary progressive MS.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment705 (estimated)
Ages18 Years to 60 Years
SexAll
SponsorZenas BioPharma (USA), LLC (industry)
Drugs / interventionsorelabrutinib
Locations2 sites (Maitland, Florida and 1 other locations)
Trial IDNCT07067463 on ClinicalTrials.gov

What this trial studies

This is a global phase 3, randomized, double-blind, parallel-group, multicenter trial comparing orelabrutinib to placebo in people with primary progressive MS. About 705 participants will be randomized 2:1 (active:placebo) and treated for roughly 30 to 60 months with a minimum of 12 months on study drug. The trial enrolls adults 18–60 years old with confirmed PPMS, documented disability progression in the prior 24 months, and EDSS between 3.0 and 6.5. Efficacy and safety outcomes will be compared between groups to determine whether orelabrutinib alters the course of disability.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18–60 with a confirmed diagnosis of primary progressive MS by 2017 McDonald criteria, EDSS 3.0–6.5, and documented disability progression in the previous 24 months who can attend study visits and meet medication restrictions.

Not a fit: Patients with relapsing-remitting or secondary progressive MS, those outside the EDSS or age ranges, those requiring anticoagulation or antiplatelet therapy, recent malignancy, major uncontrolled medical conditions, or who take strong/moderate CYP3A inhibitors are unlikely to be eligible or benefit from participation.

Why it matters

Potential benefit: If successful, orelabrutinib could slow or reduce disability progression in people with primary progressive MS.

How similar studies have performed: Other BTK inhibitors have shown promising early-phase results in multiple sclerosis—mainly in relapsing forms—so applying a CNS-penetrant BTK inhibitor to PPMS is a promising but not yet proven approach in phase 3.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* 18 to 60 years of age, inclusive
* Diagnosed with Primary Progressive MS (PPMS) according to 2017 McDonald criteria
* Participant must have documented evidence of disability progression observed during the 24 months before screening.
* Expanded disability status scale (EDSS) score between 3.0 to 6.5 points, inclusive, at Screening.

Exclusion Criteria:

* Diagnosed with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS)
* Immunologic disorder other than MS or any other conditions requiring oral, intravenous (IV), intramuscular, or intra-articular corticosteroid therapy.
* History or current diagnosis of other neurological disorders that may mimic MS
* History of any other significant active medical condition
* History of suicidal behavior within 6 months prior to Screening
* Any prior history of malignancy if no recurrence within 5 years
* Patients on anticoagulation, or antiplatelet therapy will be excluded
* Patients took strong/moderate CYP3A inhibitors or strong/moderate CYP3A inducerswithin 14 days
* Clinically significant laboratory abnormalities at Screening.
* Any allergy, contraindication, or inability to tolerate orelabrutinib or any of the excipients in the study intervention
* Vaccination with live or live-attenuated virus vaccine within 1 month prior to Screening
* History of alcohol abuse or alcohol use disorder or other drug abuse within 12 months prior to screening.

Where this trial is running

Maitland, Florida and 1 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Multiple Sclerosis Primary Progressive

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.