A Study of Orelabrutinib in Patients With 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
1 other identifier
interventional
705
11 countries
41
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Mar 2026
Typical duration for phase_3
41 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 3, 2025
CompletedFirst Posted
Study publicly available on registry
July 16, 2025
CompletedStudy Start
First participant enrolled
March 23, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 1, 2030
July 31, 2026
July 1, 2026
4.2 years
July 3, 2025
July 30, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Time to onset of composite confirmed disability progression (cCDP) , confirmed over at least 12 weeks (12-week cCDP)
* Expanded disability status scale (EDSS) score increase ≥ 1.0 point from baseline when the baseline score is ≤ 5.0, or ≥ 0.5 points from baseline when the baseline score is \> 5.0, OR * ≥ 20% increase in the Timed 25-Foot Walk Test (T25FWT), OR * ≥ 20% increase in the 9-hole Peg Test (9HPT)
Up to approximately 120 weeks
Secondary Outcomes (12)
Time to onset of composite confirmed disability progression (cCDP) , confirmed over at least 24 weeks (24-week cCDP)
Up to approximately 120 weeks
Time to onset of confirmed disability progression (CDP) , confirmed over at least 24 weeks (24-week CDP)
Up to approximately 120 weeks
MRI T2 lesion
Up to approximately 120 weeks
12-week CDP
Up to approximately 120 weeks
Time to onset of CDP defined as ≥ 20% increase on 9-hole Peg Test (9HPT) from baseline, confirmed over at least 12 weeks (12-week CDP-9HPT)
Up to approximately 120 weeks
- +7 more secondary outcomes
Study Arms (2)
Orelabrutinib Group
EXPERIMENTALPlacebo Group
PLACEBO COMPARATORInterventions
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (42)
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
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 3, 2025
First Posted
July 16, 2025
Study Start
March 23, 2026
Primary Completion (Estimated)
June 1, 2030
Study Completion (Estimated)
July 1, 2030
Last Updated
July 31, 2026
Record last verified: 2026-07