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NCT07067463PHASE3Recruiting

A Study of Orelabrutinib in Patients With Primary Progressive Multiple Sclerosis

Zenas BioPharma (USA), LLC

Start Date

3/23/2026

Completion Date

7/1/2030

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 PPMS. Patients will be treated for approximately 30 to 60 months, with a minimum treatment duration of 12 months. The study will enroll approximately 705 subjects in a 2:1 randomization (orelabrutinib: placebo), globally.

Eligibility Criteria

Age Range: 18 years to 60 years

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.

Interventions

DRUG

Orelabrutinib

DRUG

Placebo

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Conditions

Multiple Sclerosis (MS) Primary Progressive

Locations

Arizona Neuroscience Research, LLC

Pheonix, Arizona 85032

United States

Perseverance Research Center

Scottsdale, Arizona 85253

United States

Regina Berkovich MD, PhD Inc.

West Hollywood, California 90048

United States

Nova Clinical Research, LLC

Bradenton, Florida 34209

United States

Neurology Associates, PA

Maitland, Florida 32751

United States

KC Research Center, PA Neurology Research Department

Roeland Park, Kansas 66205

United States

Washington University School of Medicine

St Louis, Missouri 63110

United States

Cooperman Barnabas Medical Center

Livingston, New Jersey 07039

United States

Velocity Clinical Research, Raleigh Neurology

Raleigh, North Carolina 27607

United States

The Boster Center for Multiple Sclerosis

Columbus, Ohio 43235

United States

Premier Neurology

Greenville, South Carolina 29605

United States

Neurology Clinic, P.C.

Cordova, Tennessee 38018

United States

Lone Star Neurology

San Antonio, Texas 78258

United States

Texas Institute for Neurological Disorders

Sherman, Texas 75092

United States

Medical Center Nevrocentrum

Plovdiv, Plovdiv 4000

Bulgaria

Diagnostic and Consultative Center Convex

Sofia, Sofia 1680

Bulgaria

Avis Medica Hospital Pleven

Pleven, 5800

Bulgaria

Klinicki Bolnicki Centar Zagreb-Rebro

Zagreb, 10 000

Croatia

NEUROHK, s.r.o.

Choceň, 56501

Czechia

Astra Clinic (Clinic4U)

Tallinn, Harju 10617

Estonia

MD Georgia Staff Physician MediClub Georgia

Tbilisi, Saburtalo 0160

Georgia

NNLE Jo Ann University Hospital

Tbilisi, 0159

Georgia

Raymann, LLC

Tbilisi, 0186

Georgia

Neuro Centrum Science Gmbh Albert-Schwitzer

Erbach im Odenwald, Hesse 64711

Germany

IRCCS Istituto Neurologico Mediterraneo Neuromed

Pozzilli, Isemiaa/Molise 86077

Italy

Zuyderland Medisch Centrum - Sittard-Geleen

Sittard, Limburg 6162-BG

Netherlands

ClinHouse Centrum Medyczne

Zabrze, Pl-sl 41-807

Poland

NZOZ Novo Med

Katowice, Silesian Voivodeship 40-584

Poland

Twoja Przychodnia PCM

Poznan, Wielkopolska 60-324

Poland

Nzoz Neuro-Kard Ilkowski I Partnerzy Spolka Partnerska Lekarzy

Poznan, Wielkopolska 61-853

Poland

Galen Clinic

Lublin, 20-064

Poland

NZOZ Neuromed M. i M. Nastaj Sp.P

Lublin, 20-064

Poland

Zanamed Medical Clinic Sp.z o.o.

Lublin, 20-601

Poland

Twoja Przychodnia Centrum Medyczne Nowa Sol

Nowa Sól, 67-100

Poland

Nmedis sp.z o.o.

Rzeszów, 35-323

Poland

Euromedis Osrodek Badan Klinicznych

Szczecin, 70-111

Poland

Centrum Medyczne NeuroProtect

Warsaw, 01-684

Poland

Centrum Medyczne ProNeuro Żory

Żory, 44-240

Poland

University Clinical Centre of Kragujevac

Kragujevac, 34000

Serbia

Hospital Alvaro Cunqueiro

Vigo, Galicia 36312

Spain

Hospital Vithas Nisa Sevilla

Castilleja de la Cuesta, Seville 41950

Spain

Complejo Hospitalario Universitario A Coruna

A Coruña, 15006

Spain