A Study of Orelabrutinib in Patients With Primary Progressive Multiple Sclerosis

NCT07067463 | Recruiting Phase 3 FDA Drug

• 1 other identifier: ZB020-03-001
• Study Type: interventional
• Target: 705
• Locations: 1 country
• Sites: 2

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.

Conditions

Multiple Sclerosis (MS) Primary Progressive

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

Study Arms (2)

Orelabrutinib Group

EXPERIMENTAL

Drug: Orelabrutinib

Placebo Group

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Orelabrutinib DRUG

Orally

Orelabrutinib Group

Placebo DRUG

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
• 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.

Sponsors & Collaborators

• Zenas BioPharma (USA), LLC: lead

Study Sites (2)

Neurology Associates, PA

Maitland, Florida, 32751, United States

RECRUITING

Premier Neurology

Greenville, South Carolina, 29605, 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

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: December 1, 2025
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): July 1, 2030
• Last Updated: December 4, 2025

Record last verified: 2025-12

Locations

US (2)