A Phase 3 interventional study of Orelabrutinib and Placebo in Secondary Progressive Multiple Sclerosis, sponsored by Zenas BioPharma (USA), LLC. Recruiting at 90 sites in 20 countries. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2026-11-04.
Sponsored by Zenas BioPharma (USA), LLC · Phase 3, Interventional, and Treatment
Hungary, Ukraine, Australia, Greece, Spain, Belgium, France, Germany, Romania
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.
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:
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.
244 studies on the registry are indexed under Multiple Sclerosis, Chronic Progressive; 53 are open to participants now.
This study's planned enrollment of 990 is above the median of 54 across 189 interventional studies indexed under Multiple Sclerosis, Chronic Progressive.
Browse Multiple Sclerosis, Chronic Progressive studies →Zenas BioPharma (USA), LLC is the lead sponsor of 10 studies on the registry; 2 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Orelabrutinib PO daily
Drug: Orelabrutinib
Placebo PO daily
Drug: Placebo
Orelabrutinib orally
Placebo orally
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
Time frame: Up to approximately 120 weeks
12 Week CDP
Time to onset of CDP events on EDSS, confirmed over at least 12 weeks
Time frame: Up to approximately 120 weeks
T2 lesions on MRI
The total number of new or enlarging T2 lesions on MRI scans of the brain
Time frame: Up to approximately 120 weeks
24-week CDP-9-hole Peg Test
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
Time frame: Up to approximately 120 weeks
24-week CDP-T25FWT
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
Time frame: Up to approximately 120 weeks
24-week CDI
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
Time frame: Up to approximately 120 weeks
24-week CDI-9HPT
Time to onset of CDI events on 9HPT, defined as ≥ 20% decrease on the 9HPT score from baseline, confirmed over at least 24 weeks
Time frame: Up to approximately 120 weeks
24-week CDI-T25FWT
Time to onset of CDI events on T25FWT, defined as ≥ 20% decrease on the T25FWT score from baseline, confirmed over at least 24 weeks
Time frame: Up to approximately 120 weeks
Symbol Digit Modalities Test
The change in cognitive function as assessed by Symbol Digit Modalities Test (SDMT) from baseline to each scheduled visit
Time frame: Up to approximately 120 weeks
Annualized relapse rate
Annualized relapse rate (ARR) during the study period assessed by protocol-defined adjudicated relapses
Time frame: Up to approximately 120 weeks
To evaluate the safety and tolerability of orelabrutinib
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);
Time frame: Up to approximately 120 weeks
Not enrolling at this site — choose another above.
Hungary, Ukraine, Australia, Greece, Spain, Belgium, France, Germany, Romania
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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Studies of the drug tested here: Orelabrutinib
Multiple Sclerosis, Chronic Progressive →
Zenas BioPharma (USA), LLC