Relapsing Multiple SclerosisPhase 3FENhance 2NCT04586023
Study to Evaluate the Efficacy and Safety of Fenebrutinib Compared With Teriflunomide in Relapsing Multiple Sclerosis (RMS)
A Phase 3 study testing Fenebrutinib and Teriflunomide in people with Relapsing Multiple Sclerosis, run by Hoffmann-La Roche at 106 sites in 17 countries.
Trial 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 in a 1:1 ratio to receive either fenebrutinib or teriflunomide. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Relapsing Multiple Sclerosis
- What is being tested?
- Fenebrutinib and Teriflunomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 751 participants
- Where
- 106 sitesin 17 countries
- Study dates
- 24 Mar 2021to 9 Jul 2027
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Show all 11Show fewer
- OLE Inclusion Criteria:
- Completed the 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
Who cannot join
- 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 multiple sclerosis (PPMS) or non-active secondary progressive multiple sclerosis (SPMS)
- Any known or suspected active infection at screening, including but not limited to a positive screening tests for hepatitis B (HBV) and hepatitis C (HCV), 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
Show all 25Show fewer
- 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 (GI) 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
- Cirrhosis (Child-pugh Class A, B or C)
- Gilbert's syndrome
Trial locations and contacts
106 sites in 17 countries.
106 sites in 17 countries
Poland15 sites
NZOZ Vitamed
Bydgoszcz, 85-079
Neurocentrum Bydgoszcz sp. z o.o
Bydgoszcz, 85-796
COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika
Gdansk, 80-803
RESMEDICA Spolka z o.o.
Kielce, 25-726
Centrum Neurologii Klinicznej
Krakow, 31-505
Malopolskie Centrum Diagnostyczne MEDICAL Sp. z o. o.
Krakow, 31-637
Centrum Neurologii Krzysztof Selmaj
Lodz, 90-324
Instytut Zdrowia Dr Boczarska-Jedynak Sp. z o.o. Sp. k.
Oświęcim, 32-600
Neurologiczny Niepubliczny ZOZ Centrum Leczenia SM Osrodek Bada? Klinicznych
Plewiska, 62-064
NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek
Późna, 61-853
MedPolonia
Poznan, 60-693
Wojewódzki Szpital Specjalistyczny Nr 3
Rybnik, 44-200
Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie
Warsaw, 02-097
Wro Medica
Wroc?aw, 51-685
IBISMED Wielospecjalistyczne Centrum Medyczne
Zabrze, 41-800
Italy13 sites
Azienda Ospedaliero-Universitaria Consorziale Pol. di Bari
Bari, Apulia, 70124
Ospedale Binaghi
Cagliari, Sardinia, 09126
Universita? G. D'Annunzio
Chieti, Abruzzo, 66100
Irccs A.O.U.San Martino Ist
Genoa, Liguria, 16132
Fond. Istituto Neurologico C.Besta
Milan, Lombardy, 20133
Ospedale Civile di Montichiari
Montichiari, Lombardy, 25018
A. O. U. Federico II
Naples, Campania, 80131
AOU Policlinico Giaccone
Palermo, Sicily, 90129
IRCCS Istituto Neurologico C. Mondino?Dip. Neurologia Neuroriabilitazione S.S. Sclerosi Multipla
Pavia, Lombardy, 27100
IRCCS Istituto Neurologico Neuromed
Pozzilli, Molise, 86077
Ospedale S.Camillo Forlanini
Rome, Lazio, 00152
Policlinico Universitario A. Gemelli
Rome, Lazio, 00168
NCL Institute Neuroscience
Rome, Lazio, 00178
United States12 sites
American Health Network Institute, LLC
Avon, Indiana, 46123
University of Cincinnati
Cincinnati, Ohio, 45219
North Central Neurology Associates
Cullman, Alabama, 35058
Integrated Neurology Services PLLC
Falls Church, Virginia, 22043
Neuro Institute of New England P.C.
Foxborough, Massachusetts, 02035
University of Kansas Medical Center
Kansas City, Kansas, 66160
Hope Neurology
Knoxville, Tennessee, 37922
Medical College of Wisconsin, Inc.
Milwaukee, Wisconsin, 53226-3596
Xenoscience
Phoenix, Arizona, 85004
University of South Florida
Tampa, Florida, 33612
Los Angeles Biomedical Research Institute at Harbor-UCLA
Torrance, California, 90502
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
Brazil12 sites
Freire Pesquisa Clinica
Belo Horizonte, Minas Gerais, 30150-320
L2 Ip Instituto de Pesquisas Clinicas Ltda ME
Brasília, Federal District, 70200-730
Instituto de Neurologia de Curitiba
Curitiba, Paraná, 81210-310
Clinica Neurologica
Joinville, Santa Catarina, 89202-190
IMV Pesquisa Neurológica
Porto Alegre, Rio Grande do Sul, 90110-000
Núcleo de Pesquisa do Rio Grande do Sul
Porto Alegre, Rio Grande do Sul, 90430-001
Hospital Sao Lucas - PUCRS
Porto Alegre, Rio Grande do Sul, 90610-000
Praxis Pesquisa Médica
Santo André, São Paulo, 09090-790
CEMEC - Centro Multidisciplinar de Estudos Clínicos
São Bernardo do Campo, São Paulo, 09715-090
Centro de Pesquisas Clinicas
São Paulo, São Paulo, 01228-200
Hospital Santa Marcelina
São Paulo, São Paulo, 08270-070
Jordy Sinapse Medicina LTDA ME
São Paulo
Turkey (Türkiye)11 sites
Gazi University Medical Faculty
Ankara, 06500
Baskent Universitesi Ankara Hastanesi
Çankaya, 06490
Bakirkoy State Mental Hospital
Istanbul, 34000
Sancaktepe Training and Research Hospital
Istanbul, 34785
Selcuk University Medical Faculty
Istanbul, 42131
Kocaeli University Hospital
Kocaeli, 41380
Ege Üniversitesi Tip Fakültesi
Lzmir, 35100
Mersin University Medical Faculty
Mersin, 33079
Ondokuz Mayis University School of Medicine
Samsun, 55139
Karadeniz Tecnical Uni. Med. Fac.
Trabzon, 61080
Van Yuzuncu Yil University Hospital
Van, 65080
India8 sites
Zydus Hospital
Ahmedabad, Gujarat, 380054
Postgraduate Institute of Medical Education and Research
Chandigarh, 160012
Christian Medical College and Hospital
Ludhiana, Punjab, 141008
Seth G.S Medical College K.E.M Hospital
Mumbai, Maharashtra, 400012
Max Super Speciality Hospital
New Delhi, National Capital Territory of Delhi, 110017
Sir Gangaram Hospital
New Delhi, National Capital Territory of Delhi, 110060
Deenanath Mangeshkar Hospital & Research Centre
Pune, Maharashtra, 411004
SRM Institute of Medical Sciences
Vadapalani, Tamil Nadu, 600026
Russia7 sites
Regional clinical hospital named after prof. S.V. Ochapovsky
Krasnodar, 350086
Krasnoyarsk State Medical Academy
Krasnoyarsk, Krasnoyarsk Krai, 660022
FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency
Krasnoyarsk, Krasnoyarsk Krai, 660037
Federal center of brain research and neurotechnologies
Moskva, Moscow Oblast, 117997
Regional Clinical Hospital N.A. Semashko
Nizhny Novgorod, Niznij Novgorod, 603126
National Center of Social Significant Disease
Saint Petersburg, Sankt-Peterburg, 197110
Nebbiolo Center for Clinical Trials
Tomsk, 634009
Canada5 sites
CIUSSS du Saguenay Lac-Saint-Jean, Chicoutimi Hospital
Chicoutimi, Quebec, G7H 5H6
University of Alberta Hospital
Edmonton, Alberta, T6G 1Z1
MUCH - Montreal Neurological Institute & Hospital
Montreal, Quebec, H3A 2B4
The Ottawa Hospital - General Campus
Ottawa, Ontario, K1H 8L6
CHU de Québec
Québec, Quebec, G1J 1Z4
Mexico5 sites
Unidad de Investigación en Salud
Chihuahua City, 31203
Grupo Médico Camino S.C.
México, Mexico CITY (federal District), 03600
Mexico Centre for Clinical Research
Mexico City, Mexico CITY (federal District), 03100
Clinstile S.A de C.V.
Mexico City, Mexico CITY (federal District), 06700
Unidad de investigacion en salud (UIS)
Mexico City, 14050
France4 sites
Hopital Gabriel Montpied CHU de Clermont-Ferrand
Clermont-Ferrand, 63003
Hôpital Pasteur
Nice, 06002
Hôpital Charles Nicolle
Rouen, 76031
CHU toulouse - Hôpital Purpan
Toulouse, 31059
South Korea4 sites
Keimyung University Dongsan Medical Center
Daegu, 41931
National Cancer Center
Goyang-si, 10408
Seoul National University Hospital
Seoul, 03080
Samsung Medical Center
Seoul, 06351
Greece3 sites
Hospital Eginition
Athens, 115 28
University General Hospital of Larisa
Larissa, 411 10
AHEPA Univ. General Hospital of Thessaloniki
Thessaloniki, 54636
Bulgaria2 sites
UMHAT Dr. Georgi Stranski
Pleven, 5800
MHATNP Sveti Naum EAD
Sofia, 1113
Denmark2 sites
Sydvestjysk Sygehus Esbjerg
Esbjerg, 6700
Hjerne- og nervesygdomme, Ambulatorium, Skleroseklinikken
Sønderborg, 6400
United Kingdom1 site
Salford Royal NHS Foundation Trust
Salford, M6 8HD
About this study
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
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 in a 1:1 ratio to receive either fenebrutinib or teriflunomide. At the end of the double-blind treatment (DBT) phase (after disclosure of the DBT results), the Sponsor will determine whether or not to initiate the open-label extension (OLE) phase of the study.
- Conditions
- Relapsing Multiple Sclerosis
- Being tested
- Fenebrutinib, Teriflunomide, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FenebrutinibDrug
Participants will receive fenebrutinib.
TeriflunomideDrug
Participants will receive teriflunomide.
PlaceboDrug
Participants will receive teriflunomide-matching placebo or fenebrutinib-matching placebo.
| Study group | Role | What they receive |
|---|---|---|
| Fenebrutinib | Experimental | Participants will receive oral (PO) fenebrutinib, with teriflunomide-matching placebo. Receives: Drug: Fenebrutinib; Drug: Placebo |
| Teriflunomide | Active comparator | Participants will receive PO teriflunomide, with fenebrutinib-matching placebo in a blinded fashion. Receives: Drug: Teriflunomide; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Annualized Relapse Rate (ARR)
Measured: Minimum of 96 weeks
Secondary outcomes (12)
Time to Onset of Composite 12-week Confirmed Disability Progression (cCDP12)
Measured: Minimum of 96 weeks
Time to Onset of Composite 24-week Confirmed Disability Progression (cCDP24)
Measured: Minimum of 96 weeks
Time to Onset of 12-week Confirmed Disability Progression (CDP12)
Measured: Minimum of 96 weeks
Time to Onset of 24-week Confirmed Disability Progression (CDP24)
Measured: 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)
Measured: Baseline, Weeks 12, 24, 48 and 96
Percentage Change in Total Brain Volume From Week 24, as Assessed by MRI
Measured: From Week 24 to Week 96
Change in Participant-reported Physical Impacts of Multiple Sclerosis (MS), Measured by the Multiple Sclerosis, Impact Scale (29-Item), Version 2 (MSIS-29 v2) Physical Scale
Measured: Baseline, Weeks 12, 24, 36, 48, 60, 72, 84 and 96
Time to Onset of 12-week Confirmed 4-point Worsening in Symbol Digit Modality Test (SDMT) Score
Measured: Minimum of 96 weeks
Percent Change From Baseline to Week 48 in the Concentration of Blood Neurofilament Light (NfL) Chain
Measured: Baseline, Week 48
Time to Onset of Composite 12-week Confirmed Progression Independent of Relapse Activity (cPIRA12)
Measured: Minimum of 96 weeks
Percentage of Participants With Adverse Events (AEs)
Measured: Up to approximately 4.5 years
Plasma Concentrations of Fenebrutinib at Specified Timepoints
Measured: Up to approximately 4.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2020
- Study start24 Mar 2021
- Primary completion5 Sep 2025
- Study completion9 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Relapsing Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 751 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hoffmann-La Roche
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trials, Study director, Hoffmann-La Roche
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04586023
- Sponsor's protocol ID
- GN42272
- Other IDs
- 2020-001168-28, 2022-502618-95-00
- Acronym
- FENhance 2
- Status last verified
- Sep 2026
- First submitted
- 8 Oct 2020
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing