A Phase 3 interventional study of Orelabrutinib and Placebo in Multiple Sclerosis (MS) Primary Progressive, sponsored by Zenas BioPharma (USA), LLC. Recruiting at 86 sites in 18 countries. Open to participants aged 18 Years to 60 Years. Per ClinicalTrials.gov, last updated 2026-11-10.
Sponsored by Zenas BioPharma (USA), LLC · Phase 3, Interventional, and Treatment
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.
244 studies on the registry are indexed under Multiple Sclerosis, Chronic Progressive; 53 are open to participants now.
This study's planned enrollment of 705 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.
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.
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.
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.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
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.
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.
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.
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.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
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.
Drug: Orelabrutinib
Drug: Placebo
Orally
Orally
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)
Time frame: Up to approximately 120 weeks
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
Time to onset of confirmed disability progression (CDP) , confirmed over at least 24 weeks (24-week CDP)
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
MRI T2 lesion
The total number of new/enlarging T2 lesions on MRI scans of the brain from baseline to Week 120
Time frame: Up to approximately 120 weeks
12-week CDP
Time to onset of CDP, confirmed over at least 12 weeks
Time frame: 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)
Time frame: Up to approximately 120 weeks
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
24-week cCDI
Time to onset of composite confirmed disability improvement (cCDI) events, confirmed over at least 24 weeks
Time frame: Up to approximately 120 weeks
24-week CDI-9HPT
Time to onset of CDI 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
Time to onset of CDI on EDSS confirmed over at least 24 weeks
Time frame: Up to approximately 120 weeks
24-week CDI-T25FWT
Time to onset of CDI 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
SDMT
The change in cognitive function as assessed by Symbol Digit Modalities Test (SDMT)
Time frame: Up to approximately 120 weeks
AEs
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
Time frame: Up to approximately 120 weeks
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