NCT07299019

A Study of Orelabrutinib in Patients With 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

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 990 (estimated)
• Sponsor: Zenas BioPharma (USA), LLC · Industry
• Sex: All
• Age: 18 Years – 60 Years
• Healthy volunteers: Not accepted

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 non-active Secondary Progress MS. Patients will be treated for approximately 24 to 60 months, with a minimum treatment duration of 12 months. The study will enroll approximately 990 subjects in a 2:1 randomization (orelabrutinib: placebo), globally.

Detailed description

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.

Conditions

• Secondary Progressive Multiple Sclerosis

Interventions

Type	Name	Description
DRUG	Orelabrutinib	Orelabrutinib orally
DRUG	Placebo	Placebo orally

Timeline

• Start date: 2026-03-01
• Primary completion: 2030-06-01
• Completion: 2030-07-01
• First posted: 2025-12-23
• Last updated: 2026-03-20

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study