Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Teriflunomide in Relapsing Multiple Sclerosis (RMS) (FENhance 2)

• ClinicalTrials.gov Identifier: NCT04586023
• Recruitment Status: Recruiting
• First Posted: October 14, 2020
• Last Update Posted: May 30, 2023
• Sponsor: Hoffmann-La Roche
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: October 8, 2020
• First Posted Date: October 14, 2020
• Last Update Posted Date: May 30, 2023
• Actual Study Start Date: March 24, 2021
• Estimated Primary Completion Date: October 2, 2025 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 4, 2021): Annualized Relapse Rate (ARR) [ Time Frame: Minimum of 96 weeks ]

Original Primary Outcome Measures (submitted: October 8, 2020)

• Annualized Relapse Rate (ARR) [ Time Frame: Minimum of 96 weeks ]
• Time to onset of composite 12-week confirmed disability progression (cCDP12) [ Time Frame: Minimum of 96 weeks ]

Current Secondary Outcome Measures (submitted: March 3, 2023)

• Time to Onset of Composite 12-week Confirmed Disability Progression (cCDP12) [ Time Frame: Minimum of 96 weeks ]
• Time to Onset of Composite 24-week Confirmed Disability Progression (cCDP24) [ Time Frame: Minimum of 96 weeks ]
• Time to Onset of 12-week Confirmed Disability Progression (CDP12) [ 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 ]
• Percentage Change in Total Brain Volume from Week 24 as Assessed by MRI [ Time Frame: From Week 24 to Week 96 ]
• 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.
• 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.
• Change from Baseline to Week 48 in the Concentration of Serum Neurofilament Light chain (NfL) [ Time Frame: Up to 48 weeks ]
• Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to 4.5 years ]
• Plasma Concentrations of Fenebrutinib at Specified Timepoints [ Time Frame: Up to 4.5 years ]

Original Secondary Outcome Measures (submitted: October 8, 2020)

• Time to onset of composite 24-week confirmed disability progression (cCDP24) [ Time Frame: Minimum of 96 weeks ]
• Time to onset of 12-week confirmed disability progression (CDP12) [ 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 T1Gd+ lesions, new and/or enlarging T2-weighted lesions as detected by MRI [ Time Frame: Baseline, Weeks 12, 24, 48 and 96 ]
• Percentage Change in Total Brain Volume from Week 24 as assessed by MRI [ Time Frame: From Week 24 to Week 96 ]
• Change from Baseline in Participant-Reported Physical Impacts of Multiple Sclerosis (MS) [ Time Frame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84 and 96 ]
  Measured by the Multiple Sclerosis, 29-Item [MSIS-29] physical scale.
• Time to onset of 12-week confirmed 4-point worsening in Symbol Digit Modality Test (SDMT) score [ Time Frame: Minimum of 96 weeks ]
• Change from Baseline to Week 48 in the Concentration of Serum Neurofilament Light chain (NfL) [ Time Frame: Up to 48 weeks ]
• Percentage of Participants with Adverse Events (AEs) [ Time Frame: Up to 3.5 years ]
• Plasma Concentrations of fenebrutinib at specified timepoints [ Time Frame: Up to 3.5 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Teriflunomide in Relapsing Multiple Sclerosis (RMS)
• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Masking Description:

Sponsor will also be blinded.

Primary Purpose: Treatment

• Condition: Relapsing Multiple Sclerosis

Intervention

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

Study Arms

• Experimental: Fenebrutinib
  Participants will receive oral fenebrutinib with teriflunomide-matching placebo.
  Interventions:

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

  • Drug: Teriflunomide
  • Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 4, 2021): 736
• Original Estimated Enrollment (submitted: October 8, 2020): 734
• Estimated Study Completion Date: November 27, 2025
• Estimated Primary Completion Date: October 2, 2025 (Final data collection date for primary outcome measure)

Eligibility 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 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.
• 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 55 Years (Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Reference Study ID Number: GN42272 https://forpatients.roche.com/; 888-662-6728 (U.S. and Canada); global-roche-genentech-trials@gene.com

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

Administrative Information

• NCT Number: NCT04586023
• Other Study ID Numbers: GN42272; 2020-001168-28 ( EudraCT Number ); 2022-502618-95-00 ( Registry Identifier: EU Trial Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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).

• Current Responsible Party: Hoffmann-La Roche
• Original Responsible Party: Same as current
• Current Study Sponsor: Hoffmann-La Roche
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

• PRS Account: Hoffmann-La Roche
• Verification Date: May 2023