A Study To Evaluate The Efficacy And Safety Of Fenebrutinib Compared With Teriflunomide In Relapsing Multiple Sclerosis (RMS)

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

Sponsors

Lead Sponsor: Hoffmann-La Roche

Source Hoffmann-La Roche
Brief Summary

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.

Overall Status Not yet recruiting
Start Date December 17, 2020
Completion Date November 10, 2024
Primary Completion Date September 15, 2024
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Annualized Relapse Rate (ARR) Minimum of 96 weeks
Time to onset of composite 12-week confirmed disability progression (cCDP12) Minimum of 96 weeks
Secondary Outcome
Measure Time Frame
Time to onset of composite 24-week confirmed disability progression (cCDP24) Minimum of 96 weeks
Time to onset of 12-week confirmed disability progression (CDP12) Minimum of 96 weeks
Time to onset of 24-week confirmed disability progression (CDP24) Minimum of 96 weeks
Total Number of T1Gd+ lesions, new and/or enlarging T2-weighted lesions as detected by MRI Baseline, Weeks 12, 24, 48 and 96
Percentage Change in Total Brain Volume from Week 24 as assessed by MRI From Week 24 to Week 96
Change from Baseline in Participant-Reported Physical Impacts of Multiple Sclerosis (MS) Baseline, Weeks 12, 24, 36, 48, 60, 72, 84 and 96
Time to onset of 12-week confirmed 4-point worsening in Symbol Digit Modality Test (SDMT) score Minimum of 96 weeks
Change from Baseline to Week 48 in the Concentration of Serum Neurofilament Light chain (NfL) Up to 48 weeks
Percentage of Participants with Adverse Events (AEs) Up to 3.5 years
Plasma Concentrations of fenebrutinib at specified timepoints Up to 3.5 years
Enrollment 734
Condition
Intervention

Intervention Type: Drug

Intervention Name: fenebrutinib

Description: Participants will receive fenebrutinib.

Arm Group Label: fenebrutinib

Intervention Type: Drug

Intervention Name: teriflunomide

Description: Participants will receive teriflunomide.

Arm Group Label: teriflunomide

Intervention Type: Drug

Intervention Name: placebo

Description: Participants will receive teriflunomide-matching placebo or fenebrutinib-matching placebo.

Eligibility

Criteria:

Inclusion Criteria:

- 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).

- 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.

Exclusion Criteria:

- 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 severe renal or hepatic disease impairment.

- 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.

- 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.

OLE Inclusion Criteria:

- Completed the Double-Blind Treatment (DBT) phase of the study (remaining on study treatment; no other Disease-Modifying Therapy (DMT) administered) and who, in the opinion of the investigator, may benefit from treatment with fenebrutinib.

- Participants randomized to the teriflunomide treatment arm during the DBT phase must undergo the ATEP prior to the first administration of open-label fenebrutinib.

- 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.

Gender: All

Minimum Age: 18 Years

Maximum Age: 55 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Clinical Trials Study Director Hoffmann-La Roche
Overall Contact

Last Name: Reference Study ID Number: GN41851 www.roche.com/about_roche/roche_worldwide.htm

Phone: 888-662-6728 (U.S. and Canada)

Email: [email protected]

Verification Date

October 2020

Responsible Party

Type: Sponsor

Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: fenebrutinib

Type: Experimental

Description: Participants will receive oral fenebrutinib with teriflunomide-matching placebo.

Label: teriflunomide

Type: Active Comparator

Description: Participants will receive oral teriflunomide with fenebrutinib-matching placebo in a blinded fashion.

Acronym FENhance
Patient Data Yes
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: Double (Participant, Investigator)

Masking Description: Sponsor will also be blinded.

Source: ClinicalTrials.gov