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A Study of Orelabrutinib in Patients With Secondary Progressive Multiple Sclerosis

NCT07299019 · Zenas BioPharma (USA), LLC
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Official title
A Phase 3, Randomized, Double-blind, Efficacy and Safety Study Comparing Orelabrutinib to Placebo in Patients With Non-active Secondary Progressive Multiple Sclerosis
About this study
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.
Eligibility criteria
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 McDonald criteria 3. Participant must have a current diagnosis of SPMS in accordance with the clinical course criteria revised in 2013 4. Participant must have documented evidence of disability progression independent of clinical relapse observed during the 24 months before screening. A written summary of the clinical evidence of disability progression must be discussed and aligned between the Investigator and the Sponsor's dedicated qualified person(s). 5. Absence of clinical relapses for at least 24 months. Exclusion Criteria: 1. The patient has been diagnosed with primary progressive MS (PPMS) according to 2024 McDonald diagnostic criteria 2. Immunologic disorder other than MS or any other conditions requiring corticosteroid therapy. 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 inducers within 14 days 11. Clinically significant laboratory abnormalities at Screening. 12. Vaccination with live or live-attenuated virus vaccine within 1 month prior to Screening 13. History of alcohol abuse or alcohol use disorder or other drug abuse within 12 months prior to screening.
Study design
Enrollment target: 990 participants
Allocation: randomized
Masking: quadruple
Age groups: adult
Timeline
Starts: 2026-03-23
Estimated completion: 2030-07
Last updated: 2026-06-05
Interventions
Drug: OrelabrutinibDrug: Placebo
Primary outcomes
  • Time to onset of confirmed disability progression (CDP) events, confirmed over at least 24 weeks (Up to approximately 120 weeks)
Sponsor
Zenas BioPharma (USA), LLC · industry
Contacts & investigators
ContactPatient and Medical Information · contact · clinicaltrialsinfo@zenasbio.com · 833-269-4696
ContactPatient and Medical Information · contact · clinialtrialsinfo@zenasbio.com · 833-269-4696
All locations (12)
Arizona Neuroscience Research, LLCRecruiting
Phoenix, Arizona, United States
Perseverance Research Center, LLC (PRC)Recruiting
Scottsdale, Arizona, United States
Fullerton Neurology and Headache CenterRecruiting
Fullerton, California, United States
Regina Berkovich MD, PhD IncRecruiting
West Hollywood, California, United States
Nova Clinical Research, LLCRecruiting
Bradenton, Florida, United States
Neurology AssociatesRecruiting
Maitland, Florida, United States
KC Research Center, PA Neurology Research DeptRecruiting
Roeland Park, Kansas, United States
Boston Clinical TrialsWithdrawn
Boston, Massachusetts, United States
Profound Research LLC at Oakland Neurology CenterRecruiting
Rochester Hills, Michigan, United States
Washington University School of MedicineRecruiting
St Louis, Missouri, United States
Lone Star NeurologyRecruiting
San Antonio, Texas, United States
Texas Institute for Neurological Disorders - ShermanRecruiting
Sherman, Texas, United States
A Study of Orelabrutinib in Patients With Secondary Progressive Multiple Sclerosis · TrialPath