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.: PACTR202212815145545 Date of Registration: 21/12/2022
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A Study To Evaluate The Efficacy And Safety Of Fenebrutinib Compared With Teriflunomide In Relapsing Multiple Sclerosis (RMS) (FENhance)
Official scientific title A Phase III Multicenter Randomized, Double-Blind, Double-Dummy, Parallel-Group Study To Evaluate The Efficacy And Safety Of Fenebrutinib Compared With Teriflunomide In Adult Patients With Relapsing Multiple Sclerosis
Brief summary describing the background and objectives of the trial A study to evaluate the efficacy and safety of fenebrutinib on disability progression and relapse rate in adult participants with RMS. Eligible participants will be randomized 1:1 to either fenebrutinib or teriflunomide. Open-Label Extension (OLE) phase is contingent on a positive benefit-risk result in the Primary Analysis of the study. This study will evaluate the efficacy and safety of fenebrutinib compared with teriflunomide in adult patients with relapsing multiple sclerosis (RMS). The pharmacokinetics (PK) of fenebrutinib will also be evaluated.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) FENHANCE
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 28/02/2023
Actual trial start date
Anticipated date of last follow up 26/02/2026
Actual Last follow-up date
Anticipated target sample size (number of participants) 736
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication 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 Stratified allocation where factors such as age, gender, center, or previous treatment are used in the stratification Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group fenebrutinib fenebrutinib (200 mg by mouth [PO] BID) with teriflunomide-matching placebo fenebrutinib (200 mg by mouth [PO] BID) with teriflunomide-matching placebo fenebrutinib (200 mg by mouth [PO] BID) with teriflunomide-matching placebo 368
Control Group Active Comparator teriflunomide Drug: teriflunomide Participants will receive teriflunomide. Drug: placebo Participants will receive teriflunomide-matching placebo or fenebrutinib-matching placebo. Drug: teriflunomide Participants will receive teriflunomide. Drug: placebo Participants will receive teriflunomide-matching placebo or fenebrutinib-matching placebo. Drug: teriflunomide Participants will receive teriflunomide. Drug: placebo Participants will receive teriflunomide-matching placebo or fenebrutinib-matching placebo. 368 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
-Expanded Disability Status Scale (EDSS) score of 0 - 5.5 at screening. -A diagnosis of RMS in accordance with the revised 2017 McDonald Criteria. -Ability to complete the 9-Hole Peg Test (9-HPT) for each hand in < 240 seconds. -Ability to perform the Timed 25-Foot Walk Test (T25FWT) in <150 seconds. -For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating eggs. -For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and refrain from donating sperm. -Disease duration of > 10 years from the onset of symptoms and an EDSS score at screening < 2.0. -Female participants who are pregnant or breastfeeding, or intending to become pregnant. -Male participants who intend to father a child during the study. -A diagnosis of PPMS or non-active SPMS. -Any known or suspected active infection at screening, including but not limited to a positive screening tests for Hepatitis B and C, an active or latent or inadequately treated infection with tuberculosis (TB), a confirmed or suspected progressive multifocal leukoencephalopathy (PML). -History of cancer including hematologic malignancy and solid tumors within 10 years of screening. -Known presence of other neurological disorders, clinically significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic or gastrointestinal disease. -Rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption. -Hypoproteinemia. -Participants with several renal or hepatic disease impairment or Gilbert's Syndrome. -Participants with significantly impaired bone marrow function or significant anemia, leukopenia, neutropenia or thrombocytopenia. --Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study. History of alcohol or other drug abuse within 12 months prior to screening. --History of or currently active primary or secondary (non-drug-related) immunodeficiency, including known history of HIV infection. Inability to complete an MRI scan. -Adrenocorticotropic hormone or systemic corticosteroid therapy within 4 weeks prior to screening (inhaled and topical corticosteroids are allowed). -Receipt of a live-attenuated vaccine within 6 weeks prior to randomization. -Any previous treatment with immunomodulatory or immunosuppressive medication without an appropriate washout period. 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 29/11/2022 Aga Khan University Nairobi Institutional Scientific and Ethics Review Committee
Ethics Committee Address
Street address City Postal code Country
3rd Parklands Avenue, off Limuru Road, P 0. Box 30270, GPO 00100, Nairobi, Kenya Nairobi 00100 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Annualized Relapse Rate (ARR) [ Time Frame: Minimum of 96 weeks ] see outcome listed for the timepoint.
Secondary Outcome -Time to onset of composite 12-week confirmed disability progression (cCDP12) [ Time Frame: Minimum of 96 weeks ] -Time to onset of composite 24-week confirmed disability progression (cCDP24) [ Time Frame: Minimum of 96 weeks ] -Time to onset of 12-week confirmed disability progression (CDP12) [ Time Frame: Minimum of 96 weeks ] -Time to onset of 24-week confirmed disability progression (CDP24) [ Time Frame: Minimum of 96 weeks ] -Total Number of T1Gd+ lesions, new and/or enlarging T2-weighted lesions as detected by MRI [ Time Frame: Baseline, Weeks 12, 24, 48 and 96 ] -Percentage Change in Total Brain Volume from Week 24 as assessed by MRI [ Time Frame: From Week 24 to Week 96 ] -Change in Participant-Reported Physical Impacts of Multiple Sclerosis (MS) [ Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84 and 96 ] -Measured by the Multiple Sclerosis, 29-Item [MSIS-29] physical scale. -Time to onset of 12-week confirmed 4-point worsening in Symbol Digit Modality Test (SDMT) score [ Time Frame: Minimum of 96 weeks ] -Change from Baseline to Week 48 in the Concentration of Serum Neurofilament Light chain (NfL) [ Time Frame: Up to 48 weeks ] -Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to 3.5 years ] -Plasma Concentrations of fenebrutinib at specified timepoints [ Time Frame: Up to 3.5 years ] see outcomes listed for the timepoint.
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Aga Khan University Hospital Nairobi 3rd Parklands Avenue, Off Limuru Road Nairobi 00100 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Hoffmann La Roche 4070 Basel, Switzerland Nairobi 4070 Switzerland
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Hoffmann La Roche The Atrium, 6th Floor Chaka Road, off Lenana Road P.O. Box 44212-00100 Nairobi, Kenya Nairobi Kenya Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Saleh Mansoor mansoor.saleh@aku.edu +254709931500 Aga Khan University, Nairobi, 3rd Parklands Avenue, Nairobi-Kenya
City Postal code Country Position/Affiliation
Nairobi Kenya Professor of Hematology and Oncology
Role Name Email Phone Street address
Public Enquiries Saffra Knox saffra.knox@roche.com +447584447418 United Kingdom Off Campus, Building OFF CAMPUS
City Postal code Country Position/Affiliation
United Kingdom United Kingdom Senior Clinical Operations Lead
Role Name Email Phone Street address
Scientific Enquiries Victoria Levesque levesque.victoria@gene.com +16504169014 South San Francisco
City Postal code Country Position/Affiliation
South San Francisco Kenya Principal Clinical Scientist
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes There is a plan to share IPD. Roche commits to submit a manuscript to a peer-reviewed journal reporting primary clinical trials results no later than 18 months after the first product approval or decision to discontinue development of the product. Qualified researchers may request access to individual patient level data through the request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on Sharing of Clinical Study Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm). Clinical Study Report Roche commits to submit a manuscript to a peer-reviewed journal reporting primary clinical trials results no later than 18 months after the first product approval or decision to discontinue development of the product. Available studies are listed and available on the Vivli platform. Data requestors should use the Vivli data request form to request companies data Package(s). If approved requestors will need to sign a Data Use Agreement and the anonymized data will be shared in the Vivli secure research environment.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://vivli.org/ourmember/roche/ 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