Clinical trial NCT04586023: 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: 751
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 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

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: Cullman
country: United States
facility: North Central Neurology Associates
state: Alabama
city: Phoenix
country: United States
facility: Xenoscience
state: Arizona
city: Torrance
country: United States
facility: Los Angeles Biomedical Research Institute at Harbor-UCLA
state: California
city: Stamford
country: United States
facility: KI Health Partners, LLC
state: Connecticut
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Avon
country: United States
facility: American Health Network Institute, LLC
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Cincinnati
country: United States
facility: University of Cincinnati
state: Ohio
city: Knoxville
country: United States
facility: Hope Neurology
state: Tennessee
city: Falls Church
country: United States
facility: Integrated Neurology Services PLLC
state: Virginia
city: Milwaukee
country: United States
facility: Medical College of Wisconsin, Inc.
state: Wisconsin
city: Linz
country: Austria
facility: Kepler Universitätskliniken GmbH - Med Campus III
city: Brasilia
country: Brazil
facility: L2 Ip Instituto de Pesquisas Clinicas Ltda ME
state: Distrito Federal
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericordia
state: Minas Gerais
city: Curitiba
country: Brazil
facility: Instituto de Neurologia de Curitiba
state: Paraná
city: Porto Alegre
country: Brazil
facility: IMV Pesquisa Neurológica
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Núcleo de Pesquisa do Rio Grande do Sul
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas - PUCRS
state: Rio Grande Do Sul
city: Joinville
country: Brazil
facility: Clinica Neurologica
state: Santa Catarina
city: Santo Andre
country: Brazil
facility: Praxis Pesquisa Médica
state: São Paulo
city: Sao Bernardo Do Campo
country: Brazil
facility: CEMEC - Centro Multidisciplinar de Estudos Clínicos
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Centro de Pesquisas Clinicas
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Hospital Santa Marcelina
state: São Paulo
city: São Paulo
country: Brazil
facility: Jordy Sinapse Medicina LTDA ME
city: Pleven
country: Bulgaria
facility: UMHAT Dr. Georgi Stranski
city: Sofia
country: Bulgaria
facility: MHATNP Sveti Naum EAD
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Chicoutimi
country: Canada
facility: CIUSSS du Saguenay Lac-Saint-Jean, Chicoutimi Hospital
state: Quebec
city: Montreal
country: Canada
facility: MUCH - Montreal Neurological Institute & Hospital
state: Quebec
city: Quebec City
country: Canada
facility: CHU de Québec
state: Quebec
city: Esbjerg
country: Denmark
facility: Sydvestjysk Sygehus Esbjerg
city: Sønderborg
country: Denmark
facility: Hjerne- og nervesygdomme, Ambulatorium, Skleroseklinikken
city: Clermont-Ferrand
country: France
facility: Hopital Gabriel Montpied CHU de Clermont-Ferrand
city: Nice
country: France
facility: Hôpital Pasteur
city: Rouen
country: France
facility: Hôpital Charles Nicolle
city: Toulouse
country: France
facility: CHU toulouse - Hôpital Purpan
city: Athens
country: Greece
facility: Hospital Eginition
city: Larisa
country: Greece
facility: University General Hospital of Larisa
city: Thessaloniki
country: Greece
facility: AHEPA Univ. General Hospital of Thessaloniki
city: Ciudad Guatemala
country: Guatemala
facility: Nucare
city: New Delhi
country: India
facility: Max Super Speciality Hospital
state: Delhi
city: New Delhi
country: India
facility: Sir Gangaram Hospital
state: Delhi
city: Ahmadabad CITY
country: India
facility: Zydus Hospital
state: Gujarat
city: Mumbai
country: India
facility: Seth G.S Medical College K.E.M Hospital
state: Maharashtra
city: Pune City
country: India
facility: Sahyadri Superspeciality Hospital
state: Maharashtra
city: Pune
country: India
facility: Deenanath Mangeshkar Hospital & Research Centre
state: Maharashtra
city: Ludhiana
country: India
facility: Christian Medical College and Hospital
state: Punjab
city: Vadapalani
country: India
facility: SRM Institute of Medical Sciences
state: Tamil NADU
city: Chandigarh
country: India
facility: Postgraduate Institute of Medical Education and Research
city: Chieti
country: Italy
facility: Universita? G. D'Annunzio
state: Abruzzo
city: Napoli
country: Italy
facility: A. O. U. Federico II
state: Campania
city: Roma
country: Italy
facility: Ospedale S.Camillo Forlanini
state: Lazio
city: Roma
country: Italy
facility: Policlinico Universitario A. Gemelli
state: Lazio
city: Roma
country: Italy
facility: NCL Institute Neuroscience
state: Lazio
city: Genova
country: Italy
facility: Irccs A.O.U.San Martino Ist
state: Liguria
city: Milano
country: Italy
facility: Fond. Istituto Neurologico C.Besta
state: Lombardia
city: Montichiari
country: Italy
facility: Ospedale Civile di Montichiari
state: Lombardia
city: Pavia
country: Italy
facility: IRCCS Istituto Neurologico C. Mondino?Dip. Neurologia Neuroriabilitazione S.S. Sclerosi Multipla
state: Lombardia
city: Pozzilli
country: Italy
facility: IRCCS Istituto Neurologico Neuromed
state: Molise
city: Bari
country: Italy
facility: Azienda Ospedaliero-Universitaria Consorziale Pol. di Bari
state: Puglia
city: Cagliari
country: Italy
facility: Ospedale Binaghi
state: Sardegna
city: Palermo
country: Italy
facility: AOU Policlinico Giaccone
state: Sicilia
city: Daegu
country: Korea, Republic of
facility: Keimyung University Dongsan Medical Center
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Ciudad de México
country: Mexico
facility: Mexico Centre for Clinical Research
state: Mexico CITY (federal District)
city: Mexico City
country: Mexico
facility: Clinstile S.A de C.V.
state: Mexico CITY (federal District)
city: Mexico
country: Mexico
facility: Grupo Médico Camino S.C.
state: Mexico CITY (federal District)
city: Chihuahua
country: Mexico
facility: Unidad de Investigación en Salud
city: Ciudad de México
country: Mexico
facility: Unidad de investigacion en salud (UIS)
city: Bydgoszcz
country: Poland
facility: NZOZ Vitamed
city: Bydgoszcz
country: Poland
facility: Neurocentrum Bydgoszcz sp. z o.o
city: Gdansk
country: Poland
facility: COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika
city: Kielce
country: Poland
facility: RESMEDICA Spolka z o.o.
city: Krakow
country: Poland
facility: Centrum Neurologii Klinicznej
city: Krakow
country: Poland
facility: Malopolskie Centrum Diagnostyczne MEDICAL Sp. z o. o.
city: Lodz
country: Poland
facility: Centrum Neurologii Krzysztof Selmaj
city: Oswiecim
country: Poland
facility: Instytut Zdrowia Dr Boczarska-Jedynak Sp. z o.o. Sp. k.
city: Plewiska
country: Poland
facility: Neurologiczny Niepubliczny ZOZ Centrum Leczenia SM Osrodek Bada? Klinicznych
city: Pozna?
country: Poland
facility: NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek
city: Poznan
country: Poland
facility: MedPolonia
city: Rybnik
country: Poland
facility: Wojewódzki Szpital Specjalistyczny Nr 3
city: Warszawa
country: Poland
facility: Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie
city: Wroc?aw
country: Poland
facility: Wro Medica
city: Zabrze
country: Poland
facility: IBISMED Wielospecjalistyczne Centrum Medyczne
city: Krasnoyarsk
country: Russian Federation
facility: Krasnoyarsk State Medical Academy
state: Krasnojarsk
city: Krasnoyarsk
country: Russian Federation
facility: FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency
state: Krasnojarsk
city: Sankt-peterburg
country: Russian Federation
facility: National Center of Social Significant Disease
state: Leningrad
city: Moskva
country: Russian Federation
facility: Federal center of brain research and neurotechnologies
state: Moskovskaja Oblast
city: Nizhny Novgorod
country: Russian Federation
facility: Regional Clinical Hospital N.A. Semashko
state: Niznij Novgorod
city: Krasnodar
country: Russian Federation
facility: Regional clinical hospital named after prof. S.V. Ochapovsky
city: Tomsk
country: Russian Federation
facility: Nebbiolo Center for Clinical Trials
city: Ankara
country: Turkey
facility: Gazi University Medical Faculty
city: Istanbul
country: Turkey
facility: Bakirkoy State Mental Hospital
city: Istanbul
country: Turkey
facility: Sancaktepe Training and Research Hospital
city: Istanbul
country: Turkey
facility: Selcuk University Medical Faculty
city: Kocaeli
country: Turkey
facility: Kocaeli University Hospital
city: Lzmir
country: Turkey
facility: Ege Üniversitesi Tip Fakültesi
city: Mersin
country: Turkey
facility: Mersin University Medical Faculty
city: Samsun
country: Turkey
facility: Ondokuz Mayis University School of Medicine
city: Trabzon
country: Turkey
facility: Karadeniz Tecnical Uni. Med. Fac.
city: Van
country: Turkey
facility: Van Yuzuncu Yil University Hospital
city: Çankaya
country: Turkey
facility: Baskent Universitesi Ankara Hastanesi
city: Salford
country: United Kingdom
facility: Salford Royal NHS Foundation Trust
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: