Orelabrutinib treatment for primary progressive multiple sclerosis
Official title: A Phase 3, Randomized, Double-blind, Efficacy and Safety Study Comparing Orelabrutinib to Placebo in Patients With Primary Progressive Multiple Sclerosis
Run by Zenas BioPharma (USA), LLC · NCT07067463 · Data updated 2026-11-12
This trial tests whether orelabrutinib, a brain-penetrant BTK inhibitor, can slow disability progression in adults with primary progressive MS.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Ages | 18 Years to 60 Years |
| Sex | All |
| Enrollment | 705 (estimated) |
| Sponsor | Zenas BioPharma (USA), LLC Industry-sponsored |
| Drugs / interventions | orelabrutinib |
| Locations | 86 sites (Pheonix, Arizona and 85 other locations) |
| Status | Recruiting |
| Started | March 23, 2026 |
| Main results expected | June 2030 |
| Study ends | July 2030 |
| Registry record updated | November 10, 2026 |
| Trial ID | NCT07067463 on ClinicalTrials.gov |
Is this trial a fit for you?
✓Likely a 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.
✕Probably 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.
A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.
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.
Why it matters
Potential benefit: If successful, orelabrutinib could slow or reduce disability progression in people with primary progressive MS.
How similar studies have gone: 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.
Who can join: the full rules
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 it's running
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Arizona Neuroscience Research, LLC
Pheonix, Arizona, United States Recruiting -
Perseverance Research Center
Scottsdale, Arizona, United States Recruiting -
Regina Berkovich MD, PhD Inc.
West Hollywood, California, United States Recruiting -
Nova Clinical Research, LLC
Bradenton, Florida, United States Recruiting -
Neurology Associates, PA
Maitland, Florida, United States Recruiting -
Neurological Services of Orlando
Orlando, Florida, United States Recruiting
Show 44 more locations
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University of South Florida Department of Neurology - MS Division
Tampa, Florida, United States Recruiting -
University of Kansas Medical Center
Kansas City, Kansas, United States Recruiting -
KC Research Center, PA Neurology Research Department
Roeland Park, Kansas, United States Recruiting -
Washington University School of Medicine
St Louis, Missouri, United States Recruiting -
Cooperman Barnabas Medical Center
Livingston, New Jersey, United States Recruiting -
Velocity Clinical Research, Raleigh Neurology
Raleigh, North Carolina, United States Recruiting -
The Ohio State University Wexner Medical Center (OSUWMC)
Columbus, Ohio, United States Recruiting -
The Boster Center for Multiple Sclerosis
Columbus, Ohio, United States Recruiting -
Premier Neurology
Greenville, South Carolina, United States Recruiting -
Neurology Clinic, P.C.
Cordova, Tennessee, United States Recruiting -
Lone Star Neurology
San Antonio, Texas, United States Recruiting -
Texas Institute for Neurological Disorders - Sherman
Sherman, Texas, United States Recruiting -
Medical College of Wisconsin
Milwaukee, Wisconsin, United States Recruiting -
Neurology Network
Melbourne, Australia Recruiting -
UMHAT Dr Georgi Stranski
Pleven, Pleven, Bulgaria Recruiting -
Medical Center Nevrocentrum
Plovdiv, Plovdiv, Bulgaria Recruiting -
Diagnostic and Consultative Center Convex
Sofia, Sofia, Bulgaria Recruiting -
Medical Center Medica Plus OOD
Veliko Tarnovo, Tarnovo, Bulgaria Recruiting -
Avis Medica Hospital Pleven
Pleven, Bulgaria Recruiting -
DCC Neoclinic - Sofia
Sofia, Bulgaria Recruiting -
Medical Center Hera EOOD
Sofia, Bulgaria Recruiting -
UBC Hospital, University Of British Columbia
Vancouver, British Columbia, Canada Recruiting -
Klinicki Bolnicki Centar Zagreb-Rebro
Zagreb, Croatia Recruiting -
NEUROHK, s.r.o.
Choceň, Czechia Recruiting -
Fakultni Nemocnice Hradec Kralove
Hradec Králové, Czechia Recruiting -
Nemocnice Teplice
Teplice, Czechia Recruiting -
Astra Clinic (Clinic4U)
Tallinn, Harju, Estonia Recruiting -
MD Georgia Staff Physician MediClub Georgia
Tbilisi, Saburtalo, Georgia Recruiting -
LTD Pineo Medical Ecosystem
Tbilisi, Georgia Recruiting -
NNLE Jo Ann University Hospital
Tbilisi, Georgia Recruiting -
Caucasus Medical Center Ltd
Tbilisi, Georgia Recruiting -
Raymann, LLC
Tbilisi, Georgia Recruiting -
Zentrum fur klinische Forschung Dr.Scholl GmbH
Bad Homburg, Hesse, Germany Recruiting -
Neuro Centrum Science Gmbh Albert-Schwitzer
Erbach im Odenwald, Hesse, Germany Recruiting -
IRCCS Istituto Neurologico Mediterraneo Neuromed
Pozzilli, Isemiaa/Molise, Italy Recruiting -
Az. Osp.Universitaria Policlinico Federico II Centro Sclerosi Multipla Dip. Scienze Neurologiche
Naples, Naples, Italy Recruiting -
ARNAS Ospedali Civico Di Cristina
Palermo, Sicily, Italy Recruiting -
Universita degli Studi di Torino - Azienda Ospedaliero-Universitaria San Luigi Gonzaga - Clinica di Malattie dell'Apparato Respiratorio Neurologia & CRESM
Orbassano, Torino, Italy Recruiting -
University G. D'Annunzio of Chieti-Pescara
Chieti, Italy Recruiting -
Zuyderland Medisch Centrum - Sittard-Geleen
Sittard, Limburg, Netherlands Recruiting -
Centrum Medyczne INTERCOR Sp. z o.o.
Bydgoszcz, Kuyavian-Pomeranian Voivodeship, Poland Recruiting -
Malva Trials
Lublin, Lublin Voivodeship, Poland Recruiting -
Twoja Przychodnia Centrum Medyczne Nowa Sol
Nowa Sól, Lubusz Voivodeship, Poland Recruiting -
ClinHouse Centrum Medyczne
Zabrze, Pl-sl, Poland Recruiting
+36 more sites. See ClinicalTrials.gov for the full list.
Study contacts
- Study coordinator: Patient and Medical Information
- Email: clinicaltrialsinfo@zenasbio.com
- Phone: 833-269-4696
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How to take part
- Review the eligibility criteria above with your treating physician.
- Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
- Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.