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

A Randomized, Double-blind, Placebo-controlled Study to Investigate the Efficacy of Fenebrutinib in Relapsing Multiple Sclerosis

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Relapsing Multiple Sclerosis
• Intervention / Treatment: Drug: Placebo; Drug: Fenebrutinib

• Study Type: Interventional
• Enrollment (Actual): 109
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina, 78000
    • University Clinical Centre of the Republic of Srpska
• Croatia
  • Rijeka, Croatia, 51000
    • Clinical Hospital Center Rijeka - PPDS
  • Varaždin, Croatia, 42000
    • General Hospital Varazdin
  • Zagreb, Croatia, 10000
    • Klinicki Bolnicki Centar Zagreb
  • Zagreb, Croatia, 10000
    • Poliklinika Solmed
• Czechia
  • Brno, Czechia, 656 91
    • Fakultni nemocnice u sv. Anny v Brne
  • Hradec Králové, Czechia, 500 05
    • Fakultni nemocnice Hradec Kralove
  • Jihlava, Czechia, 58633
    • Nemocnice Jihlava
  • Prague, Czechia, 128 08
    • Vseobecna Fakultni Nemocnice V Praze - CRC - PPDS
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia
  • Belgrade, Serbia, 11040
    • Military Medical Academy
  • Kragujevac, Serbia, 34000
    • Clinical Center Kragujevac
  • Niš, Serbia, 18000
    • Clinical Center Nis
  • Zemun, Serbia, 11080
    • Clinical Hospital Centre Zemun
• Slovakia
  • Bratislava, Slovakia, 821 01
    • Univerzitna nemocnica Bratislava
• United States
  • California
    • Fullerton, California, United States, 92835
      • Fullerton Neurology and Headache Center
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Cleveland Clinic Lou Ruvo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

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 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 human immunodeficiency virus (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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fenebrutinib; Participants will receive oral fenebrutinib.	Drug: Fenebrutinib; Fenebrutinib will be administered orally.
Placebo Comparator: Placebo; Participants will receive oral placebo.	Drug: Placebo; Placebo will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
DBT Phase: New or Enlarging T2 - Weighted Lesion Rate Observed on MRI Scans of the Brain Over 12 Weeks	Radiologic evaluation for new or enlarging T2 - weighted 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. Total number of new or enlarging T2-weighted lesions were calculated as the sum of the individual number of new or enlarging lesions at Weeks 4, 8, and 12. The lesion rate (new/enlarging 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 numbers of scans.	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	Radiologic evaluation for new Gd - enhancing T1 lesion and new or enlarging T2 - weighted lesions were 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 and new or enlarging T2 - weighted lesions were calculated as the sum of the individual number of lesions observed at Weeks 4, 8 and 12. Analysis was performed using a logistic regression model performed on the status of both new T1 Gd+ lesion and new or enlarging T2-weighted lesions post-baseline (present or not) adjusted for the stratification factor(s) presence or absence of T1 Gd+ lesions on the screening MRI.	MRI scans performed at Weeks 4, 8 and 12
DBT Phase: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity, is a congenital anomaly or birth defect.	Up to Week 12
OLE Phase: Number of Participants With AEs and SAEs	An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not considered related to the medicinal (investigational) product. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability or incapacity, is a congenital anomaly or birth defect.	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)	C-SSRS=assessment tool used to assess lifetime suicidality of a participant (at baseline) as well as any new instances of suicidality (C-SSRS since last visit). Structured interview prompts recollection of suicidal ideation, including intensity of ideation, behavior, & attempts with actual/potential lethality. Categories have binary responses (yes/no) & include Wish to be Dead; Non-specific Active Suicidal Thoughts; Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act; Active Suicidal Ideation with Some Intent to Act, without Specific Plan; Active Suicidal Ideation with Specific Plan and Intent, Preparatory Acts and Behavior; Aborted Attempt; Interrupted Attempt; Actual Attempt (non-fatal); Completed Suicide. Suicidal ideation/behavior is indicated by a "yes" answer to any of the listed categories. Score of 0 is assigned if no suicide risk is present. Score of 1 or higher= suicidal ideation or behavior.	Up to Week 192
Plasma Concentrations of Fenebrutinib at Specified Timepoints		Up to Week 192

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
DBT Phase: New Gd - Enhancing T1 Lesion Rate Observed on MRI Scans of the Brain at Week 4	Radiologic evaluation for Gd enhancing T1 lesion rate was performed using a standardized MRI protocol at screening, and at Week 4. All MRI scans were read by a centralized reading center for efficacy endpoints. 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 scan performed at Week 4
DBT Phase: New Gd - Enhancing T1 Lesion Rate Observed on MRI Scans of the Brain at Week 8	Radiologic evaluation for Gd enhancing T1 lesion rate was performed using a standardized MRI protocol at screening, and at Week 8. All MRI scans were read by a centralized reading center for efficacy endpoints. 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 scan performed at Week 8
DBT Phase: New Gd - Enhancing T1 Lesion Rate Observed on MRI Scans of the Brain at Week 12	Radiologic evaluation for Gd enhancing T1 lesion rate was performed using a standardized MRI protocol at screening, and at Week 12. All MRI scans were read by a centralized reading center for efficacy endpoints. 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 scan performed at Week 12
DBT Phase: New or Enlarging T2 - Weighted Lesion Rate Observed on MRI Scans of the Brain at Week 4	Radiologic evaluation for new or enlarging T2 - weighted lesion rate was performed using a standardized MRI protocol at screening, and at Week 4. All MRI scans were read by a centralized reading center for efficacy endpoints. The lesion rate (new/enlarging 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 scan performed at Week 4
DBT Phase: New or Enlarging T2 - Weighted Lesion Rate Observed on MRI Scans of the Brain at Week 8	Radiologic evaluation for new or enlarging T2 - weighted lesion rate was performed using a standardized MRI protocol at screening, and at Week 8. All MRI scans were read by a centralized reading center for efficacy endpoints. The lesion rate (new/enlarging 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 scan performed at Week 8
DBT Phase: New or Enlarging T2 - Weighted Lesion Rate Observed on MRI Scans of the Brain at Week 12	Radiologic evaluation for new or enlarging T2 - weighted lesion rate was performed using a standardized MRI protocol at screening, and at Week 12. All MRI scans were read by a centralized reading center for efficacy endpoints. The lesion rate (new/enlarging 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 scan performed at Week 12

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2022
• Primary Completion (Actual): March 29, 2023
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: October 29, 2021
• First Submitted That Met QC Criteria: November 12, 2021
• First Posted (Actual): November 15, 2021

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis; fenebrutinib
• Other Study ID Numbers: GN43271; 2021-003772-14 (EudraCT Number); 2022-502619-13-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No