A Phase 2 Study of Orelabrutinib in Patients With Relapsing-Remitting Multiple Sclerosis

Study Overview
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Brief Summary
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This is a randomized, double-Blind, placebo-controlled Phase 2 Study of Orelabrutinib in Patients with Relapsing-Remitting Multiple Sclerosis.

Detailed Description
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The study contains 2 parts: Core Part and an Open-label Extension (OLE) Part. The Core Part is a randomized, double-blind, placebo-controlled, phase 2 study. Patients with RRMS will be randomly assigned to 1 of 4 treatment groups. placebo, orelabrutinib (low dose), orelabrutinib (medium dose) and orelabrutinib (high dose) at a 1:1:1:1 ratio. The OLE part is an open-label, single treatment arm study to enroll patients who have completed the Week 24 visit in the Core Part for continued treatment and collect additional long-term safety and efficacy data.All patients will receive the low dose of orelabrutinib or any other dose as suggested from the Core part of the study.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Phase 2 Study of Orelabrutinib in Patients With Relapsing-Remitting Multiple Sclerosis to Evaluate Efficacy, Safety, Tolerability, Pharmacokinetics, and Biological Activity

Conditions
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Relapsing Remitting Multiple Sclerosis

Intervention / Treatment
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* Other: placebo
* Drug: orelabrutinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are 18 to 55 years of age at the time of signing the informed consent. Are diagnosed with Relapsing Remitting Multiple Sclerosis (RRMS). Are neurologically stable for ≥ 30 days prior to both Screening and Baseline. One or more documented relapses within the 2 years before Screening Have an EDSS score of 0 to 5.5 at Screening and Baseline (Day 1) Women of childbearing potential must use effective method of contraception Signed and dated informed consent Patient currently participating in the Core Part who has completed the end of treatment visit and will be benefit from continued treatment per investigator's assessment. (OLE Part only) Exclusion Criteria: Diagnosed with progressive MS. Disease duration > 10 years in participants with an EDSS ≤ 2.0 at Screening and Baseline (Day 1). Immunologic disorder other than MS. History or current diagnosis of other neurological disorders that may mimic MS. History or current diagnosis of progressive multifocal leukoencephalopathy (PML). History of myocardial infarction or cerebrovascular event within 6 months prior to Screening, A history of attempted suicide within 6 months prior to Screening or a positive response to items 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) at Screening. An episode of major depression within the last 6 months prior to Screening (clinically stable minor depression is not exclusionary). History of cancer, except adequately treated basal cell or squamous cell carcinoma of the skin Breastfeeding/lactating or pregnant women Participants are excluded from participation in the study if taken prohibited medications/treatments. Participation in any investigational drug study within 6 months or 5 half-lives of the investigational drug, whichever is longest, prior to Screening. Permanent discontinuation from the Core Part due to AE/ SAE or abnormal abnormalities or conditions leading to permanent study drug discontinuation. (OLE Part only) Patient who has new abnormality appeared in the Core Part. (OLE Part only) Any significant change in the subject's medical history that would preclude administration of the study drug. (OLE Part only) Clinically significant laboratory abnormalities from the most recently available test in the Core Part that would preclude administration of the study drug. (OLE Part only)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>The Core Part：Participants receive placebo The OLE Part：Participants who have completed the Week 24 visit in the Core Part for continued treatment and collect additional long-term safety and efficacy data receive the low dose of orelabrutinib or any other dose as suggested from the Core part of the study. | Other: placebo<br>* placebo<br>Drug: orelabrutinib<br>* Orelabrutinib is a white, round, uncoated tablet<br>|
| Experimental: orelabrutinib(low dose)<br>The Core Part：Participants receive low dose orelabrutinib The OLE Part：Participants who have completed the Week 24 visit in the Core Part for continued treatment and collect additional long-term safety and efficacy data receive the low dose of orelabrutinib or any other dose as suggested from the Core part of the study. | Drug: orelabrutinib<br>* Orelabrutinib is a white, round, uncoated tablet<br>|
| Experimental: orelabrutinib(medium dose)<br>The Core Part ：Participants receive medium dose orelabrutinib The OLE Part：Participants who have completed the Week 24 visit in the Core Part for continued treatment and collect additional long-term safety and efficacy data receive the low dose of orelabrutinib or any other dose as suggested from the Core part of the study. | Drug: orelabrutinib<br>* Orelabrutinib is a white, round, uncoated tablet<br>|
| Experimental: orelabrutinib (high dose)<br>The Core Part：Participants receive high dose orelabrutinib The OLE Part：Participants who have completed the Week 24 visit in the Core Part for continued treatment and collect additional long-term safety and efficacy data receive the low dose of orelabrutinib or any other dose as suggested from the Core part of the study. | Drug: orelabrutinib<br>* Orelabrutinib is a white, round, uncoated tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The cumulative number of new GdE T1 MRI brain lesions | To evaluate the efficacy of orelabrutinib on the cumulative number of new gadolinium-enhancing (GdE) T1 magnetic resonance (MRI) brain lesions versus placebo over 12 weeks of treatment. | up to 120 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability ] | To evaluate the safety and tolerability of orelabrutinib compared to placebo in the Core Part | up to 120 weeks | 
| ARR[efficacy] | Annualized relapse rate in the OLE Part | up to 120 weeks |