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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04586010
Recruitment Status : Active, not recruiting
First Posted : October 14, 2020
Last Update Posted : April 11, 2024
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Description
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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.

Condition or disease Intervention/treatment Phase
Relapsing Multiple Sclerosis Drug: Fenebrutinib Drug: Teriflunomide Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 746 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description: Sponsor will also be blinded.
Primary Purpose: Treatment
Official 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
Actual Study Start Date : March 17, 2021
Estimated Primary Completion Date : October 2, 2025
Estimated Study Completion Date : November 27, 2025

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Arms and Interventions
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Arm Intervention/treatment
Experimental: Fenebrutinib
Participants will receive oral fenebrutinib with teriflunomide-matching placebo.
 Drug: Fenebrutinib
Participants will receive fenebrutinib.

Drug: Placebo
Participants will receive teriflunomide-matching placebo or fenebrutinib-matching placebo.
Active Comparator: Teriflunomide
Participants will receive oral teriflunomide with fenebrutinib-matching placebo in a blinded fashion.
 Drug: Teriflunomide
Participants will receive teriflunomide.

Drug: Placebo
Participants will receive teriflunomide-matching placebo or fenebrutinib-matching placebo.


Outcome Measures
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Primary Outcome Measures :
  1. Annualized Relapse Rate (ARR) [ Time Frame: Minimum of 96 weeks ]

Secondary Outcome Measures :
  1. Time to Onset of Composite 12-week Confirmed Disability Progression (cCDP12) [ Time Frame: Minimum of 96 weeks ]
  2. Time to Onset of Composite 24-week Confirmed Disability Progression (cCDP24) [ Time Frame: Minimum of 96 weeks ]
  3. Time to Onset of 12-week Confirmed Disability Progression (CDP12) [ Time Frame: Minimum of 96 weeks ]
  4. Time to Onset of 24-week Confirmed Disability Progression (CDP24) [ Time Frame: Minimum of 96 weeks ]
  5. 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 ]
  6. Percentage Change in Total Brain Volume from Week 24 as Assessed by MRI [ Time Frame: From Week 24 to Week 96 ]
  7. 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 ]
    The MSIS-29, Version 2 is a 29-item patient-reported measure of the physical and psychological impacts of MS. Participants are asked to rate how much their functioning and well-being has been impacted over the past 14 days on a 4-point scale, from "Not at all" (1) to "Extremely" (4). The physical score is the sum of items 1-20, which is then transformed to a 0-100 scale. The psychological score is the sum of items 21-29, transformed to a 0-100 scale. Higher scores indicate a greater impact of MS.

  8. Time to Onset of 12-week Confirmed 4-point worsening in Symbol Digit Modality Test (SDMT) Score [ Time Frame: Minimum of 96 weeks ]
    The SDMT is used for detecting the presence of cognitive impairment and changes in cognitive functioning over time and in response to treatment. The SDMT is brief, is easy to administer test, and involves a simple substitution task. Using a reference key, the examinee has 90 seconds to pair specific numbers with given geometric figures. Responses will be collected only orally, and administration time is approximately 5 minutes. The number of correct responses in 90 seconds will be considered the SDMT score. A decrease by 4 points on the SDMT score from baseline represents a clinically meaningful change in cognitive processing. The SDMT score ranges from 0 to 110. The higher the results, the better processing speed/working memory.

  9. Change from Baseline to Week 48 in the Concentration of Serum Neurofilament Light Chain (NfL) [ Time Frame: Up to 48 weeks ]
  10. Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to 4.5 years ]
  11. Plasma Concentrations of Fenebrutinib at Specified Timepoints [ Time Frame: Up to 4.5 years ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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 test 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.
  • 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 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04586010


Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
More Information
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04586010    
Other Study ID Numbers: GN41851
2019-004857-10 ( EudraCT Number )
2022-502609-14-00 ( Registry Identifier: EU Trial Number )
First Posted: October 14, 2020    Key Record Dates
Last Update Posted: April 11, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Teriflunomide
 Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Immunosuppressive Agents
Immunologic Factors