A Study to Investigate the Efficacy of Fenebrutinib in Relapsing Multiple Sclerosis (RMS)

NCT05119569 | Active Not Recruiting Phase 2 Results FDA Drug

• 3 other identifiers: GN432712021-003772-142022-502619-13-00
• Study Type: interventional
• Target: 109
• Locations: 6 countries
• Sites: 17

Brief Summary

This is a study evaluating the effect of fenebrutinib on brain magnetic resonance imaging (MRI) in participants with RMS. The safety and pharmacokinetics of fenebrutinib will also be evaluated. Participants will be randomized to receive either fenebrutinib or placebo. This study consists of two parts: Double-blind treatment (DBT) phase and an optional Open-label extension (OLE) phase.

Conditions

Relapsing Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• DBT Phase: New Gadolinium (Gd) - Enhancing T1 Lesion Rate Observed on Magnetic Resonance Imaging (MRI) Scans of the Brain Over 12 Weeks

  Radiologic evaluation for Gd enhancing T1 lesion rate was performed using a standardized MRI protocol at screening, and at Weeks 4, 8, and 12. All MRI scans were read by a centralized reading center for efficacy endpoints. The total number of new Gd-enhancing T1 lesions were calculated as the sum of the individual number of new lesions observed at Weeks 4, 8 and 12. The lesion rate (new lesions per scan) was estimated from a negative binomial regression model for the total number of events and was adjusted for the covariate 'presence or absence of T1 Gd+ lesions on the screening MRI'. Log-transformed number of scans were included in the negative binomial model as an "offset" variable to account for different number of scans.

  MRI scans performed at Weeks 4, 8 and 12

Secondary Outcomes (6)

• DBT Phase: New or Enlarging T2 - Weighted Lesion Rate Observed on MRI Scans of the Brain Over 12 Weeks

  MRI scans performed at Weeks 4, 8 and 12

• DBT Phase: Proportion of Participants Free From Any New Gd - Enhancing T1 Lesions and New or Enlarging T2 - Weighted Lesions Observed on MRI Scans of the Brain Over 12 Weeks

  MRI scans performed at Weeks 4, 8 and 12

• DBT Phase: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

  Up to Week 12

• OLE Phase: Number of Participants With AEs and SAEs

  OLE Baseline (DBT Week 12) up to Week 192

• Number of Participants With Post-baseline Suicidal Ideation or Suicidal Behavior as Measured Using Columbia-Suicide Severity Rating Scale (C-SSRS)

  Up to Week 192

Other Outcomes (6)

• DBT Phase: New Gd - Enhancing T1 Lesion Rate Observed on MRI Scans of the Brain at Week 4

  MRI scan performed at Week 4

• DBT Phase: New Gd - Enhancing T1 Lesion Rate Observed on MRI Scans of the Brain at Week 8

  MRI scan performed at Week 8

• DBT Phase: New Gd - Enhancing T1 Lesion Rate Observed on MRI Scans of the Brain at Week 12

  MRI scan performed at Week 12

Study Arms (2)

Fenebrutinib

EXPERIMENTAL

Participants will receive oral fenebrutinib.

Drug: Fenebrutinib

Placebo

PLACEBO COMPARATOR

Participants will receive oral placebo.

Drug: Placebo

Interventions

Fenebrutinib DRUG

Fenebrutinib will be administered orally.

Fenebrutinib

Placebo DRUG

Placebo will be administered orally.

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• A diagnosis of RMS in accordance with the revised 2017 McDonald Criteria.
• Expanded Disability Status Scale (EDSS) score of 0 - 5.5 at screening.
• 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.

You may not qualify if:

• 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 Primary Progressive Multiple Sclerosis (PPMS) or non-active Secondary Progressive Multiple Sclerosis (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.
• Presence of other neurological disorders that could interfere with the diagnosis of MS or with the assessments of safety or efficacy during the study.
• Clinically significant cardiovascular, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic or gastrointestinal disease.
• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (17)

Fullerton Neurology and Headache Center

Fullerton, California, 92835, United States

Location

Cleveland Clinic Lou Ruvo

Las Vegas, Nevada, 89106, United States

Location

University Clinical Centre of the Republic of Srpska

Banja Luka, 78000, Bosnia and Herzegovina

Location

Clinical Hospital Center Rijeka - PPDS

Rijeka, 51000, Croatia

Location

General Hospital Varazdin

Varaždin, 42000, Croatia

Location

Klinicki bolnicki centar Zagreb

Zagreb, 10000, Croatia

Location

Poliklinika Solmed

Zagreb, 10000, Croatia

Location

Fakultni nemocnice u sv. Anny v Brne

Brno, 656 91, Czechia

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Nemocnice Jihlava

Jihlava, 58633, Czechia

Location

Vseobecna Fakultni Nemocnice V Praze - CRC - PPDS

Prague, 128 08, Czechia

Location

Clinical Center of Serbia

Belgrade, 11000, Serbia

Location

Military Medical Academy

Belgrade, 11040, Serbia

Location

Clinical center Kragujevac

Kragujevac, 34000, Serbia

Location

Clinical Center Nis

Niš, 18000, Serbia

Location

Clinical Hospital Centre Zemun

Zemun, 11080, Serbia

Location

Univerzitna nemocnica Bratislava

Bratislava, 821 01, Slovakia

Location

Related Publications (1)

• Bar-Or A, Dufek M, Budincevic H, Drulovic J, Habek M, Hua LH, Weber MS, Thomas P, Napieralski J, Mitzner MC, Ratchford JN, Clayton D, Harp CT, Kuruvilla D, Qi Q, Chen YF, Xu Y, Goodyear A, Oh J; FENopta Study Group. Safety and efficacy of fenebrutinib in relapsing multiple sclerosis (FENopta): a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial and open-label extension study. Lancet Neurol. 2025 Aug;24(8):656-666. doi: 10.1016/S1474-4422(25)00174-7.

  PMID: 40683275 DERIVED

MeSH Terms

Interventions

fenebrutinib

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Sponsor will also be blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2021
• First Posted: November 15, 2021
• Study Start: March 1, 2022
• Primary Completion: March 29, 2023
• Study Completion (Estimated): December 30, 2026
• Last Updated: February 4, 2026
• Results First Posted: June 12, 2024

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (2); SE (5); SL (1); CR (4); BO (1); CZ (4)