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
Investigating the Effects of an Investigational Medication on Relapsing Multiple Sclerosis
Ajay Gupta
Primary Investigator
Brief description of study
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.
THIS STUDY IS ENROLLING BY INVITATION ONLY
Detailed description of study
All eligible patients will be randomized 1:1 to either one of two arms:
Fenebrutinib treatment arm: fenebrutinib (200 mg by mouth [PO] twice a day [BID]) with
teriflunomide matching placebo
Teriflunomide treatment arm: teriflunomide (14 mg PO once a day [QD]) with fenebrutinib
matching placebo
- Patients will take two 100 mg film-coated tablets PO BID for a total dose of 400 mg of
- fenebrutinib (or matching placebo) every day. Patients will self-administer two 100 mg tablets in
- the morning and two 100 mg tablets in the evening by mouth, for a total of 4 tablets per day.
- The comparator, teriflunomide (or matching placebo), will be administered as one 14 mg film-
- coated capsule PO QD every day. The capsule should be swallowed whole with some water,
- can be taken with or without food, and should be taken at the same time each day.
- The total duration of study participation for each individual is expected to be approximately 3.8
- years to 6.5 years, depending on when they are randomized into the study
Eligibility of study
You may be eligible for this study if you meet the following criteria:
- Conditions: Relapsing Multiple Sclerosis, RMS
-
Age: 18 years - 55 years
-
Gender: All
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.
This study investigates the effects of an investigational medication on adults with relapsing multiple sclerosis (RMS). RMS is a condition where the immune system attacks the protective covering of nerves, causing communication problems between the brain and the rest of the body. The purpose of the study is to compare the investigational medication with another treatment to see how well they work and how safe they are.
Participants will be randomly assigned to one of two study arms. One group will receive the investigational medication along with a placebo for the other treatment, while the other group will receive the other treatment with a placebo for the investigational medication. Participants will take tablets by mouth either twice a day or once a day, depending on their assigned group. The study will monitor the effects of these treatments on disability progression and relapse rates.
- Who can participate: Adults with relapsing multiple sclerosis who have an Expanded Disability Status Scale score between 0 and 5.5 may qualify. Participants must be able to perform specific physical tests within set time limits and agree to use contraception if of childbearing potential.
- Study details: Participants will take tablets by mouth, either twice a day for the investigational medication or once a day for the comparator treatment. They will follow a set schedule for taking these tablets and will be monitored for effects on their condition.
- Study timelines: The study will last approximately 3.8 to 6.5 years depending on randomization timing.
