Pan African Clinical Trials Registry

South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202208658682109 Date of Registration: 23/08/2022
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title MULTIPLE SCLEROSIS
Official scientific title A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO INVESTIGATE THE EFFICACY OF FENEBRUTINIB IN RELAPSING MULTIPLE SCLEROSIS
Brief summary describing the background and objectives of the trial MS is a chronic, inflammatory, demyelinating, and degenerative disease of the CNS that affects approximately 900,000 people in the United States (Wallin et al. 2019) and 2.3 million people worldwide (GBD 2016 Multiple Sclerosis Collaborators 2019). Traditionally, MS has been classified into three clinical phenotypes: relapsing remitting MS (RRMS), secondary progressive MS (SPMS), and primary progressive MS (PPMS) (Lublin et al. 2014). SPMS and PPMS are further subdivided into active and non-active forms based on the presence or absence of disease activity (DA), defined by the presence of clinical relapses and/or T1-weighted gadolinium-enhancing (T1Gd) lesions on magnetic resonance imaging (MRI) scan or new/enlarging T2-weighted lesions on MRI scan. Available evidence suggests that despite the potential heterogeneity of the clinical expression of the disease, PPMS, SPMS, and RRMS belong to the same disease spectrum and that pathological mechanisms responsible for relapses/DA and progression biology are largely identical across the MS spectrum (Lassmann 2019). Objectives 1. To evaluate the efficacy of fenebrutinib compared with placebo on the total number of new gadolinium-enhancing T1 MRI lesions 2. To evaluate the effect of fenebrutinib on MRI lesions 3. To evaluate the safety of fenebrutinib compared with placebo 4. To characterize the fenebrutinib PK profile
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Nervous System Diseases
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 31/01/2023
Actual trial start date
Anticipated date of last follow up 31/01/2026
Actual Last follow-up date
Anticipated target sample size (number of participants) 102
Actual target sample size (number of participants)
Recruitment status Stopped early/ terminated
Publication URL URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Central randomisation by phone/fax Masking/blinding used Care giver/Provider,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Fenebrutinib two 100 mg tablets PO BID for a total dose of 400 mg of fenebrutinib every day. 12 weeks The investigational medicinal product (IMP) for this study is fenebrutinib. Participants will take two 100 mg tablets PO BID for a total dose of 400 mg of fenebrutinib (or placebo) every day. Participants will self-administer two 100 mg tablets in the morning and two 100 mg tablets in the evening by mouth. The tablet should be swallowed whole with some water, can be taken with or without food, and should be taken at the same time each day. Participants should be instructed that a missed fenebrutinib (or matching placebo) dose should not be taken with the next scheduled dose. Administration of fenebrutinib (or matching placebo) should be staggered with antacid use (i.e., study drug should be taken 2 hours before or 2 hours after antacid administration). 68
Control Group Oral Placebo 12 weeks The control arm for the study will receive matching oral placebo. A placebo comparator was chosen to enable a clear and efficient evaluation of the safety and efficacy profile of fenebrutinib monotherapy. Given the availability of approved treatments for RMS, the period of placebo exposure should be as short as possible and should not present an inappropriate risk to participating participants. The period of placebo exposure in the DBT phase will be limited to a maximum of 12 weeks. A 2:1 randomization ratio will be used to limit the number of participants in the placebo arm. Informed consent materials will clearly explain the existence of alternative approved treatments, and that by participating in the study participants are foregoing those treatments and may receive placebo for up to 12 weeks (Polman 2008). 34 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Participants are eligible to be included in the study only if all of the following criteria apply:  Participants who are capable of giving signed informed consent and able tocomplete the study protocol  Participants who are aged 18 to 55 years inclusive at the time of signing Informed Consent Form  A diagnosis of RMS in accordance with the revised 2017 McDonald Criteria (Thompson et al. 2018) and one of the following: – At least two documented clinical relapses within the last 2 years or one documented clinical relapse within 12 months of screening (but not within the 30 days prior to screening) – Documented evidence of the presence of at least one T1 Gd+ lesion on MRI in the 6 months prior to randomization (may include the screening MRI) Note: RMS may include active secondary progressive MS as defined by Lublin 2014.  Expanded Disability Status Scale (EDSS) at screening from 0 to 5.5 points For women of childbearing potential: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use contraception, and agreement to refrain from donating eggs. For men: participants who agree to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm Participants are excluded from the study if any of the following criteria apply:  Disease duration of >10 years from the onset of symptoms and an EDSS score at screening < 2.0  Participants who are pregnant or breastfeeding, or intending to become pregnant during the study or within 28 days after the final dose of fenebrutinib. Women of childbearing potential must have a negative serum pregnancy test result at screening and negative urine pregnancy tests at all subsequent visits. If a urine pregnancy test is positive, it must be confirmed by a serum pregnancy test, ideally from the central laboratory.  Men intending to father a child during the study or within 28 days after final dose of study drug  A diagnosis of primary progressive MS or non-active secondary progressive MS  Any known or suspected active infection at screening or baseline (excluding onychomycosis), or any major episode of infection requiring hospitalization or treatment with IV anti-microbials within 8 weeks prior to or during screening or treatment with oral anti-microbials within 2 weeks prior to or during screening  History of progressive multifocal leukoencephalopathy (PML)  History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening  Presence of other neurological disorders, including, but not limited to, the following: – History of ischemic cerebrovascular disorders (e.g., stroke, transient ischemic attack, spontaneous intracranial hemorrhage, or traumatic intracranial hemorrhage) or ischemia of the spinal cord – History or known presence of CNS or spinal cord tumor (e.g., meningioma,glioma) – History or known presence of potential metabolic causes of myelopathy (e.g., untreated vitamin B12 deficiency) – History or known presence of sarcoidosis. Adult: 18 Year(s)-44 Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 55 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 02/11/2022 Aga Khan University Institutional Scientific and Ethics Review Committee
Ethics Committee Address
Street address City Postal code Country
3rd Parklands Avenue, Off Limuru Road, P.O Box 30270, Nairobi GPO 00100 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome  To evaluate the efficacy of fenebrutinib compared with placebo on the total number of new gadolinium-enhancing T1 MRI lesions Total number of new gadolinium-enhancing T1 lesions observed on MRI scans of the brain at Weeks 4, 8, and 12
Secondary Outcome To evaluate the effect of fenebrutinib on MRI lesions At Weeks 4, 8, and 12
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Aga Khan University Nairobi 3rd Parklands Avenue, Off Limuru Road, P.O Box 30270, Nairobi GPO 00100 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
F. Hoffmann La Roche Grenzacherstrasse 124 Basel Switzerland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor F. Hoffmann La Roche Grenzacherstrasse 124, Basel Switzerland Funding Agency
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Dilraj Sokhi Dilraj.Sokhi@aku.edu +254710559541 3rd Parklands
City Postal code Country Position/Affiliation
Nairobi Kenya Principal investigator
Role Name Email Phone Street address
Public Enquiries Dilraj Sohki Dilraj.Sokhi@aku.edu +254710559541 3rd Parklands
City Postal code Country Position/Affiliation
Nairobi Kenya Principal investigator
Role Name Email Phone Street address
Scientific Enquiries Dilraj Sokhi Dilraj.Sokhi@aku.edu +254710559541 3rd Parklands
City Postal code Country Position/Affiliation
Nairobi Kenya Principal Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Trial result summaries will be shared when the final clinical study report is available. The method of sharing the information is still to be determined across the entire program of studies Clinical Study Report,Informed Consent Form,Statistical Analysis Plan,Study Protocol When the clinical study report is final To be confirmed
URL Results Available Results Summary Result Posting Date First Journal Publication Date
To be provided No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information