Orelabrutinib for non-active secondary progressive multiple sclerosis

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

This trial will try daily orelabrutinib versus placebo in adults with non-active secondary progressive multiple sclerosis to see if it slows disability progression.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 990 (estimated)
• Ages: 18 Years to 60 Years
• Sex: All
• Sponsor: Zenas BioPharma (USA), LLC (Industry-sponsored)
• Drugs / interventions: Orelabrutinib
• Locations: 5 sites (Scottsdale, Arizona and 4 other locations)
• Trial ID: NCT07299019 on ClinicalTrials.gov

What this trial studies

Orelabrutinib is a brain-penetrant Bruton's tyrosine kinase (BTK) inhibitor being tested in people with non-active secondary progressive multiple sclerosis (SPMS). This phase 3, randomized, double-blind, parallel-group, multicenter trial will enroll about 990 adults and randomize them 2:1 to once-daily orelabrutinib or placebo for a treatment period that ranges from roughly 24 to 60 months, with a minimum of 12 months required for the primary analysis. Participants will be screened up to four weeks, undergo regular clinical and safety assessments, and those with 24-week confirmed disability progression by EDSS may enter a two-year open-label orelabrutinib extension, with a four-week safety follow-up after treatment discontinuation. The primary focus is on whether orelabrutinib can slow disability progression in people with non-active SPMS who have been relapse-free for at least 24 months.

Who should consider this trial

Good fit: Adults 18–60 with a prior RRMS diagnosis who now meet criteria for non-active SPMS, have documented disability progression in the past 24 months, and have had no clinical relapses for at least 24 months.

Not a fit: Patients with primary progressive MS, recent relapses, other active immunologic or neurological disorders, or who are outside the 18–60 age range are unlikely to qualify or benefit from this study.

Why it matters

Potential benefit: If successful, orelabrutinib could slow disability progression and help preserve function in people with non-active SPMS.

How similar studies have performed: Other BTK inhibitors have shown promising effects on MRI inflammation and in relapsing MS, but phase 3 evidence in non-active SPMS is limited and this specific application is relatively novel.

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.

Where this trial is running

Scottsdale, Arizona and 4 other locations

• Perseverance Research Center, LLC (PRC) — Scottsdale, Arizona, United States (Recruiting)
• Neurology Associates — Maitland, Florida, United States (Recruiting)
• Boston Clinical Trials — Boston, Massachusetts, United States (Recruiting)
• Lone Star Neurology — San Antonio, Texas, United States (Recruiting)
• Texas Institute for Neurological Disorders - Sherman — Sherman, Texas, United States (Recruiting)

Study contacts

• Study coordinator: Patient and Medical Information

Conditions Secondary Progressive Multiple Sclerosis