A Study of Orelabrutinib in Patients With Primary Progressive Multiple Sclerosis

Not Applicable

Not yet recruiting

• Conditions: Multiple Sclerosis (MS) Primary Progressive
• Interventions: Drug: Placebo; Drug: Orelabrutinib

• Registration Number: NCT07067463
• Lead Sponsor: Beijing InnoCare Pharma Tech Co., Ltd.

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 a minimum of 120 weeks. The study will enroll approximately 705 subjects in a 2:1 randomization (orelabrutinib: placebo), globally.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-07
• Study First Submitted: 2025-07-03
• Study First Submitted QC: 2025-07-14
• Last Update Submitted: 2025-07-14
• Study First Posted: 2025-07-16
• Last Update Posted: 2025-07-16
• Study Start: 2025-09-01
• Primary Completion: 2030-06
• Study Completion: 2030-07-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 705

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Group	Placebo	-
Orelabrutinib Group	Orelabrutinib	-

Primary Outcome Measures

Name	Time	Method
Time to onset of composite confirmed disability progression (cCDP) , confirmed over at least 12 weeks (12-week cCDP)	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 Outcome Measures

Name	Time	Method
Time to onset of composite confirmed disability progression (cCDP) , confirmed over at least 24 weeks (24-week cCDP)	Up to approximately 120 weeks
MRI T2 lesion	Up to approximately 120 weeks	The total number of new/enlarging T2 lesions on MRI scans of the brain from baseline to Week 120
Time to onset of confirmed disability progression (CDP) , confirmed over at least 24 weeks (24-week CDP)	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.
12-week CDP	Up to approximately 120 weeks	Time to onset of CDP, confirmed over at least 12 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
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)	Up to approximately 120 weeks
24-week CDI	Up to approximately 120 weeks	Time to onset of CDI on EDSS confirmed over at least 24 weeks
24-week cCDI	Up to approximately 120 weeks	Time to onset of composite confirmed disability improvement (cCDI) events, confirmed over at least 24 weeks
24-week CDI-9HPT	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
24-week CDI-T25FWT	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
SDMT	Up to approximately 120 weeks	The change in cognitive function as assessed by Symbol Digit Modalities Test (SDMT)
AEs	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