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

Phase 2

Active, not recruiting

• Conditions: Relapsing Remitting Multiple Sclerosis
• Interventions: Other: placebo; Drug: orelabrutinib

• Registration Number: NCT04711148
• Lead Sponsor: Beijing InnoCare Pharma Tech Co., Ltd.

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study First Submitted: 2021-01-08
• Study First Submitted QC: 2021-01-12
• Study First Posted: 2021-01-15
• Study Start: 2021-03-01
• Status Verified: 2023-03
• Last Update Submitted: 2023-04-20
• Last Update Posted: 2023-04-21
• Primary Completion: 2026-02-25
• Study Completion: 2026-03-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 160

Inclusion Criteria

1. Are 18 to 55 years of age at the time of signing the informed consent.
2. Are diagnosed with Relapsing Remitting Multiple Sclerosis (RRMS).
3. Are neurologically stable for ≥ 30 days prior to both Screening and Baseline.
4. One or more documented relapses within the 2 years before Screening
5. Have an EDSS score of 0 to 5.5 at Screening and Baseline (Day 1)
6. Women of childbearing potential must use effective method of contraception
7. Signed and dated informed consent
8. 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

1. Diagnosed with progressive MS.
2. Disease duration > 10 years in participants with an EDSS ≤ 2.0 at Screening and Baseline (Day 1).
3. Immunologic disorder other than MS.
4. History or current diagnosis of other neurological disorders that may mimic MS.
5. History or current diagnosis of progressive multifocal leukoencephalopathy (PML).
6. History of myocardial infarction or cerebrovascular event within 6 months prior to Screening,
7. 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.
8. An episode of major depression within the last 6 months prior to Screening (clinically stable minor depression is not exclusionary).
9. History of cancer, except adequately treated basal cell or squamous cell carcinoma of the skin
10. Breastfeeding/lactating or pregnant women
11. Participants are excluded from participation in the study if taken prohibited medications/treatments.
12. Participation in any investigational drug study within 6 months or 5 half-lives of the investigational drug, whichever is longest, prior to Screening.
13. Permanent discontinuation from the Core Part due to AE/ SAE or abnormal abnormalities or conditions leading to permanent study drug discontinuation. (OLE Part only)
14. Patient who has new abnormality appeared in the Core Part. (OLE Part only)
15. Any significant change in the subject's medical history that would preclude administration of the study drug. (OLE Part only)
16. 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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	placebo	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.
placebo	orelabrutinib	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.
orelabrutinib(low dose)	orelabrutinib	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.
orelabrutinib(medium dose)	orelabrutinib	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.
orelabrutinib (high dose)	orelabrutinib	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.

Primary Outcome Measures

Name	Time	Method
The cumulative number of new GdE T1 MRI brain lesions	up to 120 weeks	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.

Secondary Outcome Measures

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

Trial Locations

Locations (42)

Neurology Associates of Ormond Beach; 🇺🇸 Ormond Beach, Florida, United States

University of South Florida; 🇺🇸 Tampa, Florida, United States

Consultants in Neurology LTD; 🇺🇸 Northbrook, Illinois, United States

Neurology Associates, P.C.; 🇺🇸 Lincoln, Nebraska, United States

Premier Neurology, P.C.; 🇺🇸 Greer, South Carolina, United States

The First Affiliated Hospital of Anhui Medical University; 🇨🇳 Hefei, Anhui, China

Peking Union Medical College Hospital; 🇨🇳 Beijing, Beijing, China

Beijing Tiantan Hospital, Capital Medical University; 🇨🇳 Beijing, Beijing, China

The First Affiliated Hospital of Chongqing Medical University; 🇨🇳 Yuzhong, Chongqing, China

Tongji Hospital Tongji Medical College Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China

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