Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Teriflunomide in Relapsing Multiple Sclerosis (RMS)

• Register: ClinicalTrials.gov
• Last refreshed on: 24 March 2025
• Main ID: NCT04586023
• Date of registration: 08/10/2020
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Teriflunomide in Relapsing Multiple Sclerosis (RMS) FENhance 2
• 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
• Date of first enrolment: March 24, 2021
• Target sample size: 751
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT04586023
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 3

Countries of recruitment

Austria, Brazil, Bulgaria, Canada, Denmark, France, Greece, Guatemala, India, Italy, Korea, Republic of, Mexico, Poland, Puerto Rico, Russian Federation, Turkey, United Kingdom, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion 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) 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.

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 accelerated teriflunomide elimination procedure (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.

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 MS (PPMS) or non-active secondary progressive MS
(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, that could interfere with the
diagnosis of MS or assessments of efficacy or safety during the study and 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.

- Acute liver disease

- Chronic liver disease unless considered stable for > 6 months.

- Presence of cirrhosis (Child-Pugh Class A, B, or C) 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 human immunodeficiency virus (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.

OLE Exclusion Criteria:

- Chronic liver disease unless considered stable for > 6 months

- Acute liver disease


Age minimum: 18 Years
Age maximum: 55 Years
Gender: All

Health Condition(s) or Problem(s) studied

Relapsing Multiple Sclerosis

Intervention(s)

Drug: Placebo

Drug: Fenebrutinib

Drug: Teriflunomide

Primary Outcome(s)

Annualized Relapse Rate (ARR) [Time Frame: Minimum of 96 weeks]

Secondary Outcome(s)

Percentage Change in Total Brain Volume from Week 24 as Assessed by MRI [Time Frame: From Week 24 to Week 96]

Percentage of Participants with Adverse Events (AEs) [Time Frame: Up to 4.5 years]

Change in Participant-Reported Physical Impacts of Multiple Sclerosis (MS) Measured by the Multiple Sclerosis, 29-Item [MSIS-29] Physical Scale [Time Frame: 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 [Time Frame: Minimum of 96 weeks]

Time to Onset of Composite 12-week Confirmed Disability Progression (cCDP12) [Time Frame: Minimum of 96 weeks]

Time to Onset of Composite 12-week Confirmed Progression Independent of Relapse Activity (cPIRA12) [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 T1 Gadolinium-enhancing (Gd+) Lesions, New and/or Enlarging T2-weighted Lesions as Detected by Magnetic Resonance Imaging (MRI) [Time Frame: Baseline, Weeks 12, 24, 48 and 96]

Change from Baseline to Week 48 in the Concentration of Blood Neurofilament Light chain (NfL) [Time Frame: Up to 48 weeks]

Time to Onset of Composite 24-week Confirmed Disability Progression (cCDP24) [Time Frame: Minimum of 96 weeks]

Plasma Concentrations of Fenebrutinib at Specified Timepoints [Time Frame: Up to 4.5 years]

Time to Onset of 12-week Confirmed Disability Progression (CDP12) [Time Frame: Minimum of 96 weeks]

Secondary ID(s)

2020-001168-28

GN42272

2022-502618-95-00

Source(s) of Monetary Support

Please refer to primary and secondary sponsors