A Study of Orelabrutinib in Patients With Secondary Progressive Multiple Sclerosis

NCT07299019 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: ZB020-03-002
• Study Type: interventional
• Target: 990
• Locations: 1 country
• Sites: 5

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 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.

Conditions

Secondary Progressive Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• Time to onset of confirmed disability progression (CDP) events, confirmed over at least 24 weeks

  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

  Up to approximately 120 weeks

Secondary Outcomes (10)

• 12 Week CDP

  Up to approximately 120 weeks

• T2 lesions on MRI

  Up to approximately 120 weeks

• 24-week CDP-9-hole Peg Test

  Up to approximately 120 weeks

• 24-week CDP-T25FWT

  Up to approximately 120 weeks

• 24-week CDI

  Up to approximately 120 weeks

Study Arms (2)

Orelabrutinib Group

EXPERIMENTAL

Orelabrutinib PO daily

Drug: Orelabrutinib

Placebo Group

PLACEBO COMPARATOR

Placebo PO daily

Drug: Placebo

Interventions

Orelabrutinib DRUG

Orelabrutinib orally

Orelabrutinib Group

Placebo DRUG

Placebo orally

Placebo Group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• to 60 years of age, inclusive, at the time of signing the informed consent.
• Participant must have a previous diagnosis of RRMS in accordance with 2024 McDonald criteria
• Participant must have a current diagnosis of SPMS in accordance with the clinical course criteria revised in 2013
• 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).
• Absence of clinical relapses for at least 24 months.

You may not qualify if:

• The patient has been diagnosed with primary progressive MS (PPMS) according to 2024 McDonald diagnostic criteria
• Immunologic disorder other than MS or any other conditions requiring corticosteroid therapy.
• History or current diagnosis of other neurological disorders that may mimic MS
• History or current diagnosis of progressive multifocal leukoencephalopathy
• Active, clinically significant viral, bacterial, or fungal infection
• History of any other significant active medical condition
• History of suicidal behavior within 6 months prior to Screening
• Any prior history of malignancy
• Patients on anticoagulation, or antiplatelet therapy
• Patients took strong/moderate CYP3A inhibitors or strong/moderate CYP3A inducers within 14 days
• Clinically significant laboratory abnormalities at Screening.
• 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.

Sponsors & Collaborators

• Zenas BioPharma (USA), LLC: lead

Study Sites (5)

Perseverance Research Center, LLC (PRC)

Scottsdale, Arizona, 85253, United States

RECRUITING

Neurology Associates

Maitland, Florida, 32751, United States

RECRUITING

Boston Clinical Trials

Boston, Massachusetts, 02131, United States

RECRUITING

Lone Star Neurology

San Antonio, Texas, 78258, United States

RECRUITING

Texas Institute for Neurological Disorders - Sherman

Sherman, Texas, 75092, United States

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive

Interventions

orelabrutinib

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Patient and Medical Information

CONTACT

833-269-4696; clinicaltrialsinfo@zenasbio.com

Patient and Medical Information

CONTACT

833-269-4696; clinialtrialsinfo@zenasbio.com

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: December 18, 2025
• First Posted: December 23, 2025
• Study Start: March 23, 2026
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): July 1, 2030
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

US (5)