A Study of Orelabrutinib in Patients With Secondary Progressive Multiple Sclerosis

June 3, 2026 updated by: Zenas BioPharma (USA), LLC

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
990

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85032
        • Recruiting
        • Arizona Neuroscience Research, LLC
      • Scottsdale, Arizona, United States, 85253
        • Recruiting
        • Perseverance Research Center, LLC (PRC)
        • Principal Investigator:
          • Barry Hendin
    • California
      • Fullerton, California, United States, 92835
        • Recruiting
        • Fullerton Neurology and Headache Center
      • West Hollywood, California, United States, 90048
        • Recruiting
        • Regina Berkovich MD, PhD Inc
    • Florida
      • Bradenton, Florida, United States, 34209
        • Recruiting
        • Nova Clinical Research, LLC
      • Maitland, Florida, United States, 32751
        • Recruiting
        • Neurology Associates
    • Kansas
      • Roeland Park, Kansas, United States, 66205
        • Recruiting
        • KC Research Center, PA Neurology Research Dept
    • Massachusetts
      • Boston, Massachusetts, United States, 02131
        • Withdrawn
        • Boston Clinical Trials
    • Michigan
      • Rochester Hills, Michigan, United States, 48307
        • Recruiting
        • Profound Research LLC at Oakland Neurology Center
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Recruiting
        • Washington University School of Medicine
    • Texas
      • San Antonio, Texas, United States, 78258
        • Recruiting
        • Lone Star Neurology
        • Principal Investigator:
          • Ann Bass
      • Sherman, Texas, United States, 75092
        • Recruiting
        • Texas Institute for Neurological Disorders - Sherman
        • Principal Investigator:
          • Bharathy Sundaram
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Orelabrutinib Group
Orelabrutinib PO daily
Drug: Orelabrutinib
Orelabrutinib orally
Placebo Comparator: Placebo Group
Placebo PO daily
Drug: Placebo
Placebo orally

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Time to onset of confirmed disability progression (CDP) events, confirmed over at least 24 weeks
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
Up to approximately 120 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
12 Week CDP
Time Frame: Up to approximately 120 weeks
Time to onset of CDP events on EDSS, confirmed over at least 12 weeks
Up to approximately 120 weeks
T2 lesions on MRI
Time Frame: Up to approximately 120 weeks
The total number of new or enlarging T2 lesions on MRI scans of the brain
Up to approximately 120 weeks
24-week CDP-9-hole Peg Test
Time Frame: Up to approximately 120 weeks
Time to onset of CDP events on 9-hole Peg Test (9HPT), defined as ≥ 20% increase on 9HPT from baseline, confirmed over at least 24 weeks
Up to approximately 120 weeks
24-week CDP-T25FWT
Time Frame: Up to approximately 120 weeks
Time to onset of CDP events on Timed 25-Foot Walk Test (T25FWT), defined as ≥ 20% increase on T25FWT from baseline, confirmed over at least 24 weeks
Up to approximately 120 weeks
24-week CDI
Time Frame: Up to approximately 120 weeks
Time to onset of confirmed disability improvement (CDI) events on EDSS, defined as ≥ 1.0-point decrease on the EDSS score from baseline when the baseline score is ≤ 5.0, or ≥ 0.5 points from baseline when the baseline score is > 5.0, confirmed over at least 24 weeks
Up to approximately 120 weeks
24-week CDI-9HPT
Time Frame: Up to approximately 120 weeks
Time to onset of CDI events on 9HPT, defined as ≥ 20% decrease on the 9HPT score from baseline, confirmed over at least 24 weeks
Up to approximately 120 weeks
24-week CDI-T25FWT
Time Frame: Up to approximately 120 weeks
Time to onset of CDI events on T25FWT, defined as ≥ 20% decrease on the T25FWT score from baseline, confirmed over at least 24 weeks
Up to approximately 120 weeks
Symbol Digit Modalities Test
Time Frame: Up to approximately 120 weeks
The change in cognitive function as assessed by Symbol Digit Modalities Test (SDMT) from baseline to each scheduled visit
Up to approximately 120 weeks
Annualized relapse rate
Time Frame: Up to approximately 120 weeks
Annualized relapse rate (ARR) during the study period assessed by protocol-defined adjudicated relapses
Up to approximately 120 weeks
To evaluate the safety and tolerability of orelabrutinib
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);
Up to approximately 120 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Zenas BioPharma (USA), LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 23, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 1, 2030

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 18, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 19, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 23, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 5, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 3, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ZB020-03-002

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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