A Study of Orelabrutinib in Patients With Relapsing-Remitting Multiple Sclerosis (RRMS)
- Conditions
- MedDRA version: 21.1Level: PTClassification code 10063399Term: Relapsing-remitting multiple sclerosisSystem Organ Class: 10029205 - Nervous system disordersTherapeutic area: Diseases [C] - Nervous System Diseases [C10]Relapsing-Remitting Multiple Sclerosis
- Registration Number
- EUCTR2020-005117-41-PL
- Lead Sponsor
- InnoCare Pharma, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 160
For the Core Part:
Age:
1. 18 to 55 years of age at the time of signing the informed consent.
Type of Participant and Disease Characteristics:
2. Diagnosed with Relapsing Remitting Multiple Sclerosis (RRMS) in accordance with 2017 Revised McDonald criteria.
3. Neurologically stable for = 30 days prior to both Screening and Baseline.
4. One or more documented relapses within the 2 years before Screening with either:
a. one relapse which occurred within the last year prior to randomization, OR
b. the presence of at least 1 Gd+ T1 lesion on MRI within 6 months prior to randomization.
5. An EDSS step of 0 to 5.5 at Screening and Baseline (Day 1)
a. Patients with an EDSS step = 2 at Screening and Baseline (Day 1) are only eligible for participation if their disease duration (time since onset of symptoms) is no more than 10 years.
6. Women of childbearing potential must agree to use a supplementary barrier method together with a highly effective method of contraception (according to ICH guidance M3[R2]) for 4 weeks prior to randomization, throughout the trial, and for 90 days after the last dose of investigational medicinal product (IMP).
Informed Consent:
7. Signed and dated informed consent (patient must be able to understand the informed consent) indicating that the patient has been informed of all the pertinent aspects of the trial prior to enrollment and will comply with the requirements of the protocol
8. Patients must be contactable by email or telephone throughout the study.
For the OLE Part:
1. Written informed consent must be obtained before any assessment is performed.
2. Patient currently participating in the Core Part who has completed the end of treatment visit (the Week 24 visit) and will be benefit from continued treatment per investigator's assessment.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 160
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
For the Core Part:
Medical Conditions:
1. Progressive MS
2. Disease duration > 10 years in patients with an EDSS = 2.0
3. Immunologic disorder other than MS
4. Other neurological disorders that may mimic MS
5. Progressive multifocal leukoencephalopathy (PML)
6. Significant infection
7. Active TB
8. Gilbert's disease, chronic liver disease or pre-existing or potential risk factors for hepatic dysfunction
9. Hemophilia OR serious bleeding OR coagulopathy
10. Splenectomy
11. Significant active medical condition in the Investigator’s opinion and in agreement with the Medical Monitor
12. Attempted suicide
13. Major depression
14. History of cancer
15. Breastfeeding/lactating or pregnant women
16. Any abnormality on Screening electrocardiogram (ECG); or clinically significant prolonged QTc interval, or QTc interval >470 ms in women and >450 ms in men at screening
17. Any other clinically significant abnormality per Investigator opinion
Prior/Concomitant Therapy:
18. Glucocorticoids, or ACTH within 4 weeks prior to randomization
19. Beta-interferons or glatiramer acetate within 4 weeks prior to randomization
20. Dimethyl fumarate, diroximel fumarate, or other fumaric acid esters within 4 weeks prior to randomization
21. Teriflunomide and leflunomide within 4 weeks if an accelerated elimination procedure AEP is performed or 14 weeks without the completion of an Accelerated Elimination Procedure (AEP) prior to randomization
22. Natalizumab within 3 months prior to randomization
23. Use of S1P agents within 12 weeks prior to randomization
24. IV immunoglobulin (Ig) or plasmapheresis within 12 weeks prior to randomization.
25. Daclizumab, BTK inhibitors, mitoxantrone, or lymphocyte-depleting therapies
26. Cyclophosphamidewithin 36 months (3 years) prior to randoization and azathioprine within 6 months prior to randomization.
27.Tacrolimus, cyclosporin, methotrexate, and mycophenolate mofetil
within 3 months prior to randomization.
28 Dalfampridine (Ampyra®) or fampridine can be included only if they have been on a stable dose for 3 months prior to randomization
29. Medical marijuana
30. On anticoagulation, or antiplatelet therapy, or NSAIDs used regularly
31. Strong to moderate inducers of CYP3A or strong to moderate inhibitors of CYP3A
Prior/Concurrent Clinical Study Experience:
32. Participation in any investigational drug study within 6 months or 5 half-lives of the investigational drug, whichever is longest, prior to Screening
Diagnostic Assessments:
33. Any of the following:
a. History of or positive for HIV at Screening
b. History of or positive for HCV antibody at Screening
c. Positive for hepatitis B surface antigen (HBsAg) and/or positive for hepatitis B core antibody (HBcAb) at Screening
34. GFR < 30 mL/min/1.73 m2
35. ALT, AST, or total bilirubin >ULN of laboratory reference range; amylase, or lipase >2×ULN OR total bilirubin >1.5×ULN or any other clinically significant laboratory abnormality; or any pre- existing liver diseases, including but not limited to viral hepatitis, alcoholic hepatitis and steatosis, nonalcoholic steatohepatitis, cirrhosis,
autoimmune hepatitis
36. Neutrophil count < 1,500 / mm3, platelet count < 75,000 / mm3, absolute lymphocyte count < 1,000 / mm3, or a white blood cell count < 3,500 / mm3
37. INR= 1.5 or APTT= 1.5 x ULN
38. B cell CD19 count below the lower limit of normal range
Other Exclusions:
39. Any allergy, contraindication, or inability to tolerate orelabrutinib
40. Inability to c
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To evaluate the efficacy of orelabrutinib on the cumulative number of new gadolinium-enhancing (Gd+) T1 magnetic resonance (MRI) brain lesions versus placebo over 12 weeks of treatment.;Secondary Objective: - To evaluate the efficacy of orelabrutinib on clinical symptoms and imaging measures. <br>- To evaluate the safety and tolerability of orelabrutinib. <br>;Primary end point(s): Cumulative number of new G+ T1 brain lesions at Week 12 (based on T1-weighted MRI scans at Weeks 4, 8, 12) compared to placebo.;Timepoint(s) of evaluation of this end point: Week 12
- Secondary Outcome Measures
Name Time Method