Skip to main content
OpenTrials
Recruiting

NCT Number: NCT07067463

A Study of Orelabrutinib in Patients With Primary Progressive Multiple Sclerosis

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.

Recruiting

Interested in participating?

Request Info

Key information

Conditions

Multiple Sclerosis (MS) Primary Progressive Autoimmune Diseases Autoimmune Diseases of the Nervous System Chronic Disease Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Disease Attributes Immune System Diseases Multiple Sclerosis Multiple Sclerosis, Chronic Progressive Nervous System Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Medical Center Nevrocentrum, Plovdiv, Bulgaria

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 18 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.

Exclusion criteria

  • 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.

Treatment and study plan

Orelabrutinib

Drug

Orally

Placebo

Drug

Orally

Primary outcomes

  1. Time to onset of composite confirmed disability progression (cCDP) , confirmed over at least 12 weeks (12-week cCDP)

    Time frame: Up to approximately 120 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, OR
    • ≥ 20% increase in the Timed 25-Foot Walk Test (T25FWT), OR
    • ≥ 20% increase in the 9-hole Peg Test (9HPT)

Secondary outcomes

  1. Time to onset of composite confirmed disability progression (cCDP) , confirmed over at least 24 weeks (24-week cCDP)

    Time frame: Up to approximately 120 weeks

  2. Time to onset of confirmed disability progression (CDP) , confirmed over at least 24 weeks (24-week CDP)

    Time frame: Up to approximately 120 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.

  3. MRI T2 lesion

    Time frame: Up to approximately 120 weeks

    The total number of new/enlarging T2 lesions on MRI scans of the brain from baseline to Week 120

  4. 12-week CDP

    Time frame: Up to approximately 120 weeks

    Time to onset of CDP, confirmed over at least 12 weeks

  5. 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)

    Time frame: Up to approximately 120 weeks

  6. Time to onset of CDP defined as ≥ 20% increase on Timed 25-Foot Walk Test (T25FWT) from baseline, confirmed over at least 12 weeks (12-week CDP-T25FWT)

    Time frame: Up to approximately 120 weeks

  7. 24-week cCDI

    Time frame: Up to approximately 120 weeks

    Time to onset of composite confirmed disability improvement (cCDI) events, confirmed over at least 24 weeks

  8. 24-week CDI-9HPT

    Time frame: Up to approximately 120 weeks

    Time to onset of CDI on 9HPT defined as ≥ 20% decrease on the 9HPT score from baseline, confirmed over at least 24 weeks

  9. 24-week CDI

    Time frame: Up to approximately 120 weeks

    Time to onset of CDI on EDSS confirmed over at least 24 weeks

  10. 24-week CDI-T25FWT

    Time frame: Up to approximately 120 weeks

    Time to onset of CDI on T25FWT defined as ≥ 20% decrease on the T25FWT score from baseline, confirmed over at least 24 weeks

  11. SDMT

    Time frame: Up to approximately 120 weeks

    The change in cognitive function as assessed by Symbol Digit Modalities Test (SDMT)

  12. AEs

    Time frame: Up to approximately 120 weeks

    Safety as assessed by the nature, severity, and incidence of adverse events (AEs) (graded according to National Cancer Institute-Common Terminology Criteria for AEs, NCI-CTCAE version 5.0); vital signs; electrocardiograms (ECGs); and clinical laboratory safety parameter

Study contacts

Contact information is provided by the study sponsor or research team.

Patient and Medical Information

CONTACT

[email protected]

833-269-4696

Sponsors and collaborators

Lead sponsor

Zenas BioPharma (USA), LLC

Industry

Registry information

Official study title

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

Important dates

Study start
2026
Primary completion
2030
Study completion
2030
First posted
Jul 16, 2025
Registry last updated
Jul 28, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.