Clinical trial NCT04586010: A 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Relapsing Multiple Sclerosis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2020-10-14
Enrollment: 746
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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. At the end of the DBT phase (after disclosure of the DBT results), the Sponsor will determine whether or not to initiate the open-label extension phase of the study.


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.

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 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.
* 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:

* Acute liver disease
* Chronic liver disease unless considered stable for \> 6 months

Primary outcomes:
measure: Annualized Relapse Rate (ARR)
timeFrame: Minimum of 96 weeks
Secondary outcomes:
measure: Time to Onset of Composite 12-week Confirmed Disability Progression (cCDP12)
timeFrame: Minimum of 96 weeks
measure: Time to Onset of Composite 24-week Confirmed Disability Progression (cCDP24)
timeFrame: Minimum of 96 weeks
measure: Time to Onset of 12-week Confirmed Disability Progression (CDP12)
timeFrame: Minimum of 96 weeks
measure: Time to Onset of 24-week Confirmed Disability Progression (CDP24)
timeFrame: Minimum of 96 weeks
measure: Total Number of T1 Gadolinium Enhancing (Gd+) Lesions, New and/or Enlarging T2-weighted Lesions as Detected by Magnetic Resonance Imaging (MRI)
timeFrame: Baseline, Weeks 12, 24, 48 and 96
measure: Percentage Change in Total Brain Volume from Week 24 as Assessed by MRI
timeFrame: From Week 24 to Week 96
measure: Change in Participant-Reported Physical Impacts of Multiple Sclerosis (MS) Measured by the Multiple Sclerosis, 29-Item [MSIS-29] Physical Scale
timeFrame: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84 and 96
measure: Time to Onset of 12-week Confirmed 4-point worsening in Symbol Digit Modality Test (SDMT) Score
timeFrame: Minimum of 96 weeks
measure: Change from Baseline to Week 48 in the Concentration of Blood Neurofilament Light Chain (NfL)
timeFrame: Up to 48 weeks
measure: Percentage of Participants with Adverse Events (AEs)
timeFrame: Up to 4.5 years
measure: Plasma Concentrations of Fenebrutinib at Specified Timepoints
timeFrame: Up to 4.5 years
measure: Time to Onset of Composite 12-week Confirmed Progression Independent of Relapse Activity (cPIRA12)
timeFrame: Minimum of 96 weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: Homewood
country: United States
facility: Alabama Neurology Associates
state: Alabama
city: Phoenix
country: United States
facility: Center for Neurology and Spine - Phoenix - Hunt - PPDS
state: Arizona
city: Carlsbad
country: United States
facility: Profound Research, LLC
state: California
city: Irvine
country: United States
facility: University of California Irvine
state: California
city: Pasadena
country: United States
facility: SC3 Research Group, Inc
state: California
city: Aurora
country: United States
facility: University of Colorado Denver
state: Colorado
city: Denver
country: United States
facility: Mountain View Clinical Research
state: Colorado
city: Fort Collins
country: United States
facility: Advanced Neurology of Colorado, LLC
state: Colorado
city: Maitland
country: United States
facility: Neurology Associates, PA; Research Department
state: Florida
city: Highland Park
country: United States
facility: NorthShore University HealthSystem
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Neurological Center
state: Indiana
city: Baton Rouge
country: United States
facility: The NeuroMedical Center
state: Louisiana
city: Shreveport
country: United States
facility: Ochsner LSU Health
state: Louisiana
city: Baltimore
country: United States
facility: Johns Hopkins University School Of Medicine; Outpatient Center
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Teaneck
country: United States
facility: Holy Name Hospital; Institute For Clinical Research
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico; MS Specialty Clinic
state: New Mexico
city: Centerville
country: United States
facility: Miami Valley Hospital South; Dayton Physician's Office
state: Ohio
city: Columbus
country: United States
facility: OhioHealth
state: Ohio
city: Columbus
country: United States
facility: The Boster Center for MS
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Medical Research Foundation; MS Center of Excellence
state: Oklahoma
city: Bethlehem
country: United States
facility: St. Luke's University Health network
state: Pennsylvania
city: Greenville
country: United States
facility: Premier Neurology
state: South Carolina
city: Knoxville
country: United States
facility: New Orleans Center for Clinical Research
state: Tennessee
city: Plano
country: United States
facility: North Texas Institute of Neurology and Headache NextStage Clinical Research Clinic
state: Texas
city: Sherman
country: United States
facility: Texas Institute for Neurological Disorders
state: Texas
city: Vienna
country: United States
facility: Multiple Sclerosis Center of Greater Washington
state: Virginia
city: Kirkland
country: United States
facility: Evergreen MS Center
state: Washington
city: Milwaukee
country: United States
facility: Wheaton Franciscan Healthcare - St. Francis Outpatient Center; Center for Neurological Disorders
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: IME - Instituto Médico Especializado
city: Buenos Aires
country: Argentina
facility: Centro de Especialidades Neurológicas y Rehabilitación - CENyR
city: C. A. B. A.
country: Argentina
facility: CIER
city: Ciudad Autonoma de Buenos Aires
country: Argentina
facility: Instituto de Investigaciones Metabolicas (Idim)
city: Rosario
country: Argentina
facility: Diagnostico Medico Oroño
city: San Juan
country: Argentina
facility: Cer San Juan
city: San Miguel de Tucuman
country: Argentina
facility: Centro de Investigaciones Médicas Tucuman
city: Beijing City
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Beijing Tiantan Hospital,Capital Medical University
city: Changchun
country: China
facility: the First Hospital of Jilin University
city: Changsha City
country: China
facility: Xiangya Hospital Central South University
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
city: Chongqing
country: China
facility: The First Affiliated Hospital, Chongqing Medical University
city: Guangzhou City
country: China
facility: The First Affiliated Hospital of Sun Yat-sen University
city: Guangzhou City
country: China
facility: The second Affiliated Hospital of Guangzhou Medical University
city: Guiyang
country: China
facility: The affiliated Hospital of Guiyang Medical College
city: Kunming City
country: China
facility: The First People?s Hospital of Yunnan Province
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
city: Suzhou City
country: China
facility: The First Affiliated Hospital of Soochow University
city: Taiyuan
country: China
facility: 1st Affiliated Hospital of Shanxi Medical University
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
city: Urumqi City
country: China
facility: Xinjiang People Hospital
city: Wuhan City
country: China
facility: Tongji Hospital Tongji Medical College Huazhong University of Science and Technology
city: Xi'an
country: China
facility: Tangdu Hospital, The Fourth Military Medical University
city: Santiago de los Caballeros
country: Dominican Republic
facility: NeuroINC
city: Santo Domingo
country: Dominican Republic
facility: Hospital Padre Billini
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital
city: Tbilisi
country: Georgia
facility: New Hospitals
city: Tbilisi
country: Georgia
facility: Pineo Medical Ecosystem
city: Tbilisi
country: Georgia
facility: St. Michael hospital
city: Tbilisi
country: Georgia
facility: MediClab Georgia
city: Tbilisi
country: Georgia
facility: Khechinashvili University Hospital
city: Berlin
country: Germany
facility: Jüdisches Krankenhaus Berlin
city: Böblingen
country: Germany
facility: Studienzentrum Dr. Bischof GmbH
city: Dresden
country: Germany
facility: Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften
city: Gießen
country: Germany
facility: Universitätsklinikum Gießen und Marburg GmbH
city: Kiel
country: Germany
facility: Uniklinik Schleswig-Holstein
city: Stuttgart
country: Germany
facility: Praxis Dr. med. Andreas Kowalik, Arzt für Neurologie und Psychiatrie
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen, Zentrum für Neurologie
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Westerstede
country: Germany
facility: Studienzentrum Nordwest Dr med Joachim Springub Herr Wolfgang Schwarz
city: Hong Kong
country: Hong Kong
facility: Pamela Youde Nethersole Eastern Hospital
city: Shatin, New Territories
country: Hong Kong
facility: Prince of Wales Hospital
city: Budapest
country: Hungary
facility: Clinexpert Kft.
city: Budapest
country: Hungary
facility: S-Medicon Egeszsegugyi Szolgaltato Kft.
city: Eger
country: Hungary
facility: Markhot Ferenc Oktatokorhaz és Rendelointezet
city: Kistarcsa
country: Hungary
facility: Pest Megyei Flor Ferenc Korhaz
city: Szeged
country: Hungary
facility: Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ
city: Napoli
country: Italy
facility: AOU Seconda Università degli Studi
state: Campania
city: Napoli
country: Italy
facility: AOU Policlinico - Università L. Vanvitelli
state: Campania
city: Parma
country: Italy
facility: A.O.U. di Parma
state: Emilia-Romagna
city: Roma
country: Italy
facility: Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla
state: Lazio
city: Roma
country: Italy
facility: Policlinico Umberto I
state: Lazio
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant'Andrea
state: Lazio
city: Bergamo
country: Italy
facility: ASST PAPA GIOVANNI XXIII Neurologia USS Malattie Autoimmuni Centro Sclerosi Multipla
state: Lombardia
city: Milano
country: Italy
facility: IRCCS Ospedale San Raffaele
state: Lombardia
city: Mondovì (CN)
country: Italy
facility: Ospedale Regina Montis Regalis
state: Piemonte
city: Foggia
country: Italy
facility: AO.U. Policlinico Riuniti Foggia
state: Puglia
city: Catania
country: Italy
facility: AOU Policlinico V. Emanuele - P.O G. Rodolico
state: Sicilia
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
state: Veneto
city: Nairobi
country: Kenya
facility: Aga Khan University Hospital
city: Saltillo
country: Mexico
facility: Clinical Research Institute Saltillo
state: Coahuila
city: Cdmx
country: Mexico
facility: Health Pharma Professional Research
state: Mexico CITY (federal District)
city: Mexico City
country: Mexico
facility: Grupo Medico de Investigacion Clinica Multidisciplinaria
state: Mexico CITY (federal District)
city: Culiacán
country: Mexico
facility: Neurociencias Estudios Clinicos S.C.
state: Sinaloa
city: Mexico
country: Mexico
facility: Hospital General de Mexico
state: Tlaxcala
city: Sittard-Geleen
country: Netherlands
facility: Zuyderland Medisch Centrum - Sittard Geleen
city: Skopje
country: North Macedonia
facility: PHO General City Hospital 8th September Center for dialysis
city: Skopje
country: North Macedonia
facility: University Clinic for Neurology - Skopje
city: Stip
country: North Macedonia
facility: Clinical Hospital Stip
city: Bellavista
country: Peru
facility: Hospital IV Alberto Sabogal Sologuren
city: La Victoria, Lima
country: Peru
facility: Hospital Nacional Guillermo Almenara Irigoyen
city: Lima
country: Peru
facility: Hospital Nacional Dos de Mayo
city: LIma
country: Peru
facility: Clinica Internacional Sede Lima
city: Lima
country: Peru
facility: Hospital Maria Auxiliadora
city: Pueblo Libre
country: Peru
facility: Clinica Centenario Peruano Japonesa
city: ?ory
country: Poland
facility: ProNeuro Centrum Medyczne
city: Bydgoszcz
country: Poland
facility: Neurocentrum Bydgoszcz sp. z o.o
city: Katowice
country: Poland
facility: Care Clinic
city: Krosno
country: Poland
facility: MT Medic Krosno
city: Lodz
country: Poland
facility: Centrum Neurologii Krzysztof Selmaj
city: Lublin
country: Poland
facility: Rodzinne Centrum Medyczne Lubimed.pl
city: Plewiska
country: Poland
facility: Neurologiczny Niepubliczny ZOZ Centrum Leczenia SM Osrodek Bada? Klinicznych
city: Poznan
country: Poland
facility: MedPolonia
city: Warszawa
country: Poland
facility: Instytut Psychiatrii i Neurologii II Klinika Neurologiczna
city: Zabrze
country: Poland
facility: IBISMED Wielospecjalistyczne Centrum Medyczne
city: Braga
country: Portugal
facility: Hospital de Braga
city: Coimbra
country: Portugal
facility: HUC
city: Lisboa
country: Portugal
facility: Hospital Santo Antonio dos Capuchos
city: Lisboa
country: Portugal
facility: Hospital da Luz
city: Porto
country: Portugal
facility: Hospital Geral de Santo Antonio
city: Porto
country: Portugal
facility: Hospital de Sao Joao
city: Santa Maria Da Feira
country: Portugal
facility: Centro Hospitalar Entre o Douro e Vouga E.P.E. - Hospital de São Sebastião
city: UFA
country: Russian Federation
facility: Republican clinical hospital named after G.G. Kuvatov
state: Baskortostan
city: St Petersburg
country: Russian Federation
facility: Leningrad Regional Clinical Hospital
state: Sankt Petersburg
city: St Petersburg
country: Russian Federation
facility: Pavlov State Medical Uni
state: Sankt Petersburg
city: Ulyanovsk
country: Russian Federation
facility: Ulyanovsk Regional Clinical Hospital
state: Uljanovsk
city: Kirov
country: Russian Federation
facility: Center of Cardiology and Neurology
city: Novosibirsk
country: Russian Federation
facility: FSBIH Siberian Regional Medical Centre of FMBA of Russia
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital Universitari de Bellvitge
state: Barcelona
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Quiron de Madrid
state: Madrid
city: EL Palmar (EL Palmar)
country: Spain
facility: Hospital Universitario Virgen de Arrixaca
state: Murcia
city: Vigo
country: Spain
facility: Hospital Alvaro Cunqueiro
state: Pontevedra
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: Hospital Universitario de la Princesa
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga ? Hospital General
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Bern
country: Switzerland
facility: Inselspital Bern Medizin Neurologie
city: Lugano
country: Switzerland
facility: Ospedale Regionale di Lugano - Civico
city: Mannouba
country: Tunisia
facility: Hopital Razi
city: Monastir
country: Tunisia
facility: Fattouma Bourguiba Hospital
city: Sfax
country: Tunisia
facility: Hospital Habib Bourguiba
city: Lviv
country: Ukraine
facility: MNE Lviv Territorial Medical Association Clinical Hospital for Palliative Care
state: Chernihiv Governorate
city: Zaporizhia
country: Ukraine
facility: LCC "Medical center "Unimed"
state: Katerynoslav Governorate
city: Vinnytsia
country: Ukraine
facility: Salutem Medical Center
state: KIEV Governorate
city: Dnipro
country: Ukraine
facility: Separated structural unit ?University hospital? of Dnipro State Medical University
state: Tavria Okruha
city: Dnipro
country: Ukraine
facility: SI USSRI of Medical and Social Problems of Disabilities of MOHU
city: Kharkov
country: Ukraine
facility: Ams of Ukraine
city: Kyiv
country: Ukraine
facility: Medical Center of Private Execution First Private Clinic
city: Kyiv
country: Ukraine
facility: Medical Center Dopomoga Plus
city: Lviv
country: Ukraine
facility: Lviv Regional Clinical Hospital
city: Odesa
country: Ukraine
facility: Odesa Regional Clinical Hospital
city: Vinnytsi
country: Ukraine
facility: Medical Clinical Research Center of Medical Center LLC Health Clinic
city: Zaporizhzhia
country: Ukraine
facility: Municipal Non-profit Enterprise Zaporizhzhya Regional Hospital Zaporizhzhya Regional Council
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: