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

Phase 2Active Not RecruitingNCT05119569

Hoffmann-La Roche109 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

109

Conditions

Relapsing Multiple Sclerosis

Interventions

FenebrutinibDRUG

Fenebrutinib will be administered orally.

PlaceboDRUG

Placebo will be administered orally.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 Years

Medical Language ↔ Plain English

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 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.

Locations (17)

Fullerton Neurology and Headache Center

Fullerton, California, United States

Cleveland Clinic Lou Ruvo

Las Vegas, Nevada, United States

Outcomes

Primary Outcomes

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.

Time frame: MRI scans performed at Weeks 4, 8 and 12

Secondary Outcomes

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.

Time frame: 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.

Data from ClinicalTrials.gov

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