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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Relapsing Remitting Multiple Sclerosis
• Intervention / Treatment: Other: placebo; Drug: orelabrutinib

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 Type: Interventional
• Enrollment (Anticipated): 160
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230022
      • The First Affiliated Hospital of Anhui Medical University
  • Beijing
    • Beijing, Beijing, China, 100070
      • Beijing Tiantan Hospital, Capital Medical University
    • Beijing, Beijing, China, 100032
      • Peking Union Medical College Hospital
  • Chongqing
    • Yuzhong, Chongqing, China, 400016
      • The First Affiliated Hospital of Chongqing Medical University
  • Hubei
    • Wuhan, Hubei, China, 430060
      • Tongji Hospital Tongji Medical College Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital, Central South University
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Liaoning
    • Shengyang, Liaoning, China, 110004
      • Shengjing Hospital of China Medical University
  • Shanghai
    • Shanghai, Shanghai, China, 200040
      • Huashan Hospital, Fudan University
  • Shanxi
    • Taiyuan, Shanxi, China
      • The 1st Affiliated Hospital of Shanxi Medical University
    • Xi'an, Shanxi, China, 710038
      • The Second Affiliated Hospital of Air Force Military Medical University
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310009
      • The Second Affiliated Hospital of Zhejiang University School of Medicine
• Poland
  • Katowice, Poland, 40-123
    • NZOZ Wielospecjalistyczna Poradnia Lekarska "Synapsis"
  • Katowice, Poland, 40-571
    • Prywatna Praktyka Lekarska
  • Kielce, Poland, 25-726
    • Resmedica NZOZ Kielce
  • Krakow, Poland, 31-637
    • MCD Medical
  • Lublin, Poland, 20-954
    • NeuroMed
  • Poznan, Poland, 61-853
    • NZOZ "Neuro-kard"
  • Zabrze, Poland, 41-807
    • Wielospecjalistyczne Centrum Medyczne Ibismed
• Ukraine
  • Dnipro, Ukraine, 49005
    • CE I.I.Mechnykov Dnipropetrovsk RC Hosp of Dnipropetrovsk RC Dept of Neurology
  • Dnipro, Ukraine, 49027
    • Medical Center of Dnipro State Medical University, Dnipro State Medical University
  • Dnipro, Ukraine, 49027
    • SI USSRI of Medical and Social Problems of Disabilities of MOHU
  • Ivano-Frankivsk, Ukraine, 76008
    • CNE Regional Clinical Hospital of Ivano-Frankivsk Regional Council
  • Kharkiv, Ukraine, 61068
    • SI Institute of Neurology, Psychiatry and Narcology of NAMSU
  • Kharkiv, Ukraine, 61068
    • Institute of Neurology, Psychiatry and Narcology of NAMSU
  • Kharkiv, Ukraine, 61172
    • CIH Kharkiv City General Practice
  • Kyiv, Ukraine, 3110
    • Medical Center of Limited Liability Company Medbud-Clinic
  • Lviv, Ukraine, 79010
    • CNE of Lviv Reg Council Lviv Reg Clin Hospital Dept of Neurology D.Halytskyi Lviv NMU
  • Lviv, Ukraine, 79013
    • CNE City Clinical Hospital #5 of Lviv
  • Odesa, Ukraine, 65025
    • CNE Odesa Regional Clinical Hospital of Odesa Regional Council
  • Vinnytsia, Ukraine, 21009
    • Medical Center of Limited Liability Company Health Clinic, Medical Clinical Research Center
  • Vinnytsia, Ukraine, 21050
    • Medical Center of Limited Liability Company Medical Center Saliutem
  • Zaporizhzhia, Ukraine, 69035
    • Municipal Non-profit Enterprise "City Hospital No.6" of Zaporizhzya City Council
  • Zaporizhzhia, Ukraine, 69600
    • CNE Zaporizhzhia RCH of ZRC Dept of Neurology #1
  • Zaporizhzhia, Ukraine, 69600
    • CNE Zaporizhzhia Regional Clinical Hospital of ZRC
  • Zaporizhzhya, Ukraine, 69035
    • Medical Center of Limited Liability Company INET-09
• United States
  • Florida
    • Ormond Beach, Florida, United States, 32174
      • Neurology Associates of Ormond Beach
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Illinois
    • Northbrook, Illinois, United States, 60062
      • Consultants in Neurology Ltd
  • Nebraska
    • Lincoln, Nebraska, United States, 68510
      • Neurology Associates, P.C.
  • South Carolina
    • Greer, South Carolina, United States, 29650
      • Premier Neurology, P.C.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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.	Other: placebo; placebo; Drug: orelabrutinib; Orelabrutinib is a white, round, uncoated tablet
Experimental: orelabrutinib(low dose); 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; Orelabrutinib is a white, round, uncoated tablet
Experimental: orelabrutinib(medium dose); 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; Orelabrutinib is a white, round, uncoated tablet
Experimental: orelabrutinib (high dose); 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; Orelabrutinib is a white, round, uncoated tablet

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak concentration (Cmax)	Dose Escalation Peak concentration (Cmax)	up to 120 weeks

Collaborators and Investigators

• Sponsor: Beijing InnoCare Pharma Tech Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2021
• Primary Completion (Anticipated): February 25, 2026
• Study Completion (Anticipated): March 1, 2026

Study Registration Dates

• First Submitted: January 8, 2021
• First Submitted That Met QC Criteria: January 12, 2021
• First Posted (Actual): January 15, 2021

Study Record Updates

• Last Update Posted (Actual): April 21, 2023
• Last Update Submitted That Met QC Criteria: April 20, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting
• Other Study ID Numbers: ICP-CL-00112

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No