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FENhance: Study To Evaluate The Efficacy And Safety Of Fenebrutinib Compared With Teriflunomide In Relapsing Multiple Sclerosis (RMS)

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04586023
Collaborator
(none)
736
Enrollment
129
Locations
2
Arms
56.1
Anticipated Duration (Months)
5.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
736 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Masking Description:
Sponsor will also be blinded.
Primary Purpose:
Treatment
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
Actual Study Start Date :
Mar 24, 2021
Anticipated Primary Completion Date :
Oct 2, 2025
Anticipated Study Completion Date :
Nov 27, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: fenebrutinib

Participants will receive oral fenebrutinib with teriflunomide-matching placebo.

Drug: fenebrutinib
Participants will receive fenebrutinib.

Drug: placebo
Participants will receive teriflunomide-matching placebo or fenebrutinib-matching placebo.
Active Comparator: teriflunomide

Participants will receive oral teriflunomide with fenebrutinib-matching placebo in a blinded fashion.

Drug: teriflunomide
Participants will receive teriflunomide.

Drug: placebo
Participants will receive teriflunomide-matching placebo or fenebrutinib-matching placebo.

Outcome Measures

Primary Outcome Measures

  1. Annualized Relapse Rate (ARR) [Minimum of 96 weeks]

Secondary Outcome Measures

  1. Time to onset of composite 12-week confirmed disability progression (cCDP12) [Minimum of 96 weeks]

  2. Time to onset of composite 24-week confirmed disability progression (cCDP24) [Minimum of 96 weeks]

  3. Time to onset of 12-week confirmed disability progression (CDP12) [Minimum of 96 weeks]

  4. Time to onset of 24-week confirmed disability progression (CDP24) [Minimum of 96 weeks]

  5. Total Number of T1Gd+ lesions, new and/or enlarging T2-weighted lesions as detected by MRI [Baseline, Weeks 12, 24, 48 and 96]

  6. Percentage Change in Total Brain Volume from Week 24 as assessed by MRI [From Week 24 to Week 96]

  7. Change in Participant-Reported Physical Impacts of Multiple Sclerosis (MS) [Baseline, Weeks 12, 24, 36, 48, 60, 72, 84 and 96]

    Measured by the Multiple Sclerosis, 29-Item [MSIS-29] physical scale.

  8. Time to onset of 12-week confirmed 4-point worsening in Symbol Digit Modality Test (SDMT) score [Minimum of 96 weeks]

  9. Change from Baseline to Week 48 in the Concentration of Serum Neurofilament Light chain (NfL) [Up to 48 weeks]

  10. Percentage of Participants with Adverse Events (AEs) [Up to 3.5 years]

  11. Plasma Concentrations of fenebrutinib at specified timepoints [Up to 3.5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 55 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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 PPMS or non-active 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, 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.

  • Participants with severe renal or hepatic disease impairment 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 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 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 North Central Neurology Associates Cullman Alabama United States 35058
2 Xenoscience Phoenix Arizona United States 85004
3 Stanford University Medical Center; Stanford Neuroscience Health Center Stanford California United States 94305
4 Los Angeles Biomedical Research Institute at Harbor-UCLA Torrance California United States 90502
5 KI Health Partners, LLC; New England Institute for Clinical Research Stamford Connecticut United States 06905
6 SFM Clinical Research, LLC Boca Raton Florida United States 33487
7 University of South Florida Tampa Florida United States 33612
8 American Health Network Institute, LLC Avon Indiana United States 46123
9 University of Kansas Medical Center Kansas City Kansas United States 66160
10 Neuro Institute of New England P.C.; Research Foxboro Massachusetts United States 02035
11 Memorial Healthcare Institute for Neurosciences and Multiple Sclerosis Owosso Michigan United States 48867
12 NeuroScience Research Center Canton Ohio United States 44718
13 University of Cincinnati; Department of Neurology Cincinnati Ohio United States 45267
14 Providence Neurological Specialties Portland Oregon United States 97225
15 Geisinger Medical Center Danville Pennsylvania United States 17822
16 Allegheny Neurological Associates Pittsburgh Pennsylvania United States 15212
17 Hope Neurology Knoxville Tennessee United States 37922
18 Baylor College of Medicine Houston Texas United States 77030
19 Central Texas Neurology Consultants Round Rock Texas United States 78681
20 Integrated Neurology Services PLLC Falls Church Virginia United States 22043
21 Medical College of Wisconsin, Inc. Milwaukee Wisconsin United States 53226-3596
22 Kepler Universitätskliniken GmbH - Med Campus III; Neurologie & Psychiatrie Linz Austria 4021
23 Medizinische Universität Wien; Univ.Klinik fuer Neurologie Wien Austria 1090
24 L2 Ip Instituto de Pesquisas Clinicas Ltda ME; Centro Medico Hospitalar Brasilia DF Brazil 70200-730
25 Santa Casa de Misericordia; de Belo Horizonte Belo Horizonte MG Brazil 30150-221
26 Instituto de Neurologia de Curitiba Curitiba PR Brazil 81210-310
27 Hospital Universitario Clementino Fraga Filho - UFRJ Rio de Janeiro RJ Brazil 21941-913
28 IMV Pesquisa Neurológica Porto Alegre RS Brazil 90110-000
29 Núcleo de Pesquisa do Rio Grande do Sul Porto Alegre RS Brazil 90430-001
30 Hospital Sao Lucas - PUCRS Porto Alegre RS Brazil 90610-000
31 Clinica Neurologica; Neurocirurgica de Joinville Joinville SC Brazil 89202-190
32 Hospital das Clinicas - UNICAMP Campinas SP Brazil 13083-887
33 Praxis Pesquisa Médica Santo Andre SP Brazil 09090-790
34 CEMEC - Centro Multidisciplinar de Estudos Clínicos Sao Bernardo Do Campo SP Brazil 09715-090
35 Centro de Pesquisas Clinicas; CPCLIN Sao Paulo SP Brazil 01228-200
36 Jordy Sinapse Medicina LTDA ME Sao Paulo SP Brazil 04515-000
37 Hospital Santa Marcelina; AME - Ambulatório de Especialidades Médicas Sao Paulo SP Brazil 08270-070
38 UMHAT Dr. Georgi Stranski; 2nd Neurology Clinic, Occupational Diseases Pleven Bulgaria 5800
39 MHATNP Sveti Naum EAD Sofia Bulgaria 1113
40 University of Alberta Hospital Edmonton Alberta Canada T6G 1Z1
41 The Ottawa Hospital - General Campus; Department of Neurology - Multiple Sclerosis Ottawa Ontario Canada K1H 8L6
42 CIUSSS du Saguenay Lac-Saint-Jean, Chicoutimi Hospital Chicoutimi Quebec Canada G7H 5H6
43 Recherche Sepmus, Inc. Greenfield Park Quebec Canada J4V 2J2
44 MUCH - Montreal Neurological Institute & Hospital Montreal Quebec Canada H3A 2B4
45 Hjerne- og nervesygdomme, Ambulatorium, Skleroseklinikken Aabenraa Denmark 6200
46 Aalborg Universitetshospital; Neurologisk Afdeling og Neurofysiologisk Afdeling; Skleroseamb. Aalborg Denmark 9000
47 Sydvestjysk Sygehus Esbjerg; Neurologisk Afd., Skleroseklinikken Esbjerg Denmark 6700
48 Hopital Pellegrin-CHU de Bordeaux; Service de Neurologie Bordeaux France 33076
49 Hopital Gabriel Montpied CHU de Clermont-Ferrand; Service de Neurologie B Clermont-Ferrand France 63003
50 Hopital européen de Marseille; Neurologie Marseille France 13003
51 Hopital Gui de Chauliac; Neurologie Montpellier France 34295
52 Hôpital Pasteur; Service de Neurologie Nice France 06002
53 Hôpital Charles Nicolle; Service de Neurologie Rouen France 76031
54 CHU toulouse - Hôpital Purpan; Departement de Neurologie Toulouse France 31059
55 University General Hospital of Larisa; Neurology Clinic Larisa Greece 411 10
56 AHEPA Univ. General Hospital of Thessaloniki; B' Neurology Dept. Thessaloniki Greece 546 36
57 Hospital Eginition; First Department of Neurology Αθηνα Greece 115 28
58 University General Hospital of Ioannina; Neurology Clinic Ιωαννινα Greece 455 00
59 Nucare Ciudad Guatemala Guatemala 01015
60 Nucare Ciudad Guatemala Guatemala 01015
61 Sir Gangaram Hospital NEW Delhi Delhi Delhi India 110060
62 Deenanath Mangeshkar Hospital & Research Centre Pune Maharashtra India 411004
63 Fortis Escorts Hospital Jaipur Rajasthan India 302017
64 Universita' G. D'Annunzio; Dipartimento di Neuroscienze, Imaging e Scienze Cliniche Chieti Abruzzo Italy 66100
65 A. O. U. Federico II; Dip Neuroscienze, Scienze Riproduttive ed Odontostomatologiche Napoli Campania Italy 80131
66 Ospedale S.Camillo Forlanini; UOSD Day Hospital Neurologico e Neurochirurgico Roma Lazio Italy 00152
67 Policlinico Universitario A. Gemelli; UOC Neurologia - Centro Sclerosi Multipla Roma Lazio Italy 00168
68 NCL Institute Neuroscience Roma Lazio Italy 00178
69 Irccs A.O.U.San Martino Ist; Dinogmi Genova Liguria Italy 16132
70 Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico; UOSD Malattie Neurodegenerative Milano Lombardia Italy 20122
71 Fond. Istituto Neurologico C.Besta; UO Neurologia IV - Neuroimmunologia Malattie Neuromuscolari Milano Lombardia Italy 20133
72 Ospedale Civile di Montichiari; Centro Sclerosi Multipla Montichiari Lombardia Italy 25018
73 IRCCS Istituto Neurologico C. Mondino-Dip. Neurologia Neuroriabilitazione S.S. Sclerosi Multipla Pavia Lombardia Italy 27100
74 IRCCS Istituto Neurologico Neuromed; Centro per lo Studio e la Cura della Sclerosi Multipla Pozzilli Molise Italy 86077
75 Ospedale Binaghi; Centro Sclerosi Multipla Cagliari Sardegna Italy 09126
76 AOU Policlinico Giaccone; UOC Neurologia e Neurofisiopatologia-Amb Sclerosi Multipla Palermo Sicilia Italy 90129
77 Keimyung University Dongsan Medical Center Daegu Korea, Republic of 41931
78 National Cancer Center Goyang-si Korea, Republic of 10408
79 Seoul National University Hospital Seoul Korea, Republic of 03080
80 Samsung Medical Center Seoul Korea, Republic of 06351
81 Mexico Centre for Clinical Research Ciudad de México Mexico CITY (federal District) Mexico 03100
82 Grupo Médico Camino S.C. Ciudad de México Mexico CITY (federal District) Mexico 03600
83 Clinstile S.A de C.V. Mexico City Mexico CITY (federal District) Mexico 06700
84 Unidad de Investigación en Salud; Psiquiatria Chihuahua Mexico 31203
85 Unidad de investigacion en salud (UIS); Neurociencias Ciudad de México Mexico 14050
86 NZOZ Vitamed Bydgoszcz Poland 85-079
87 Neurocentrum Bydgoszcz sp. z o.o Bydgoszcz Poland 85-796
88 COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika; Oddział Neurologiczny Gdansk Poland 80-803
89 Gornoslaskie Centrum Medyczne Katowice Poland 40-635
90 RESMEDICA Spolka z o.o. Kielce Poland 25-726
91 Centrum Neurologii Klinicznej Krakow Poland 31-505
92 Malopolskie Centrum Diagnostyczne MEDICAL Sp. z o. o. Krakow Poland 31-637
93 MT Medic Krosno Krosno Poland 38-400
94 Centrum Neurologii Krzysztof Selmaj Lodz Poland 90-324
95 Indywidualna Praktyka Lekarska Prof. Dr Hab. N. Med. Konrad Rejdak. Lublin Poland 20-016
96 Wojewodzki Szpital Specjalistyczny Olsztyn Poland 10-561
97 Instytut Zdrowia Dr Boczarska-Jedynak Sp. z o.o. Sp. k. Oswiecim Poland 32-600
98 Neurologiczny Niepubliczny ZOZ Centrum Leczenia SM Osrodek Badań Klinicznych Plewiska Poland 62-064
99 MedPolonia Poznan Poland 60-693
100 NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek Poznań Poland 61-853
101 Wojewódzki Szpital Specjalistyczny Nr 3 Rybnik Poland 44-200
102 Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie Warszawa Poland 02-097
103 Instytut Psychiatrii i Neurologii II Klinika Neurologiczna Warszawa Poland 02-957
104 EMC Instytut Medyczny S.A. Wrocław Poland 50-220
105 Wro Medica Wrocław Poland 51-685
106 IBISMED Wielospecjalistyczne Centrum Medyczne Zabrze Poland 41-800
107 San Juan MS Center Guaynabo Puerto Rico 00968
108 FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency Krasnoyarsk Krasnojarsk Russian Federation 660037
109 Krasnoyarsk State Medical Academy Krasnoyarsk Krasnojarsk Russian Federation 660049
110 National Center of Social Significant Disease Sankt-peterburg Leningrad Russian Federation 197110
111 Federal center of brain research and neurotechnologies Moskva Moskovskaja Oblast Russian Federation 117997
112 Regional clinical hospital named after prof. S.V. Ochapovsky Krasnodar Russian Federation 350086
113 Regional Clinical Hospital N.A. Semashko; Neurology Nizhny Novgorod Russian Federation 603126
114 State Novosibirsk Regional Clinical Hospital Novosibirsk Russian Federation 630087
115 Nebbiolo Center for Clinical Trials Tomsk Russian Federation 634009
116 Regional Multiple Sclerosis Centre b/o CC ECM Neftyanik; Neurology Tyumen Russian Federation 625000
117 Hacettepe University Medical Faculty; Neurology Ankara Turkey 06100
118 Gazi University Medical Faculty; Departmant of Neurology. Ankara Turkey 06500
119 Bakirkoy State Mental Hospital Istanbul Turkey 34000
120 Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi; Noroloji Anabilim Dali Istanbul Turkey 34098
121 Sancaktepe Training and Research Hospital; Neurology Istanbul Turkey 34785
122 Kocaeli University Hospital; Department of Neurology Kocaeli Turkey 41380
123 Selcuk University Medical Faculty; Norology department Konya Turkey 42131
124 Ege Üniversitesi Tip Fakültesi Lzmir Turkey 35100
125 Mersin University Medical Faculty; Neurology Mersin Turkey 33079
126 Ondokuz Mayis University School of Medicine; Neurology Samsun Turkey 55139
127 Karadeniz Tecnical Uni. Med. Fac.; Neurology Trabzon Turkey 61080
128 Van Yuzuncu Yil University Hospital; Neurology Van Turkey 65080
129 Salford Royal NHS Foundation Trust Salford United Kingdom M6 8HD

Sponsors and Collaborators

  • Hoffmann-La Roche

Investigators

  • Study Director: Clinical Trials, Hoffmann-La Roche

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT04586023
Other Study ID Numbers:
  • GN42272
  • 2020-001168-28
First Posted:
Oct 14, 2020
Last Update Posted:
Aug 4, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Multiple Sclerosis
Sclerosis
Teriflunomide

Study Results

No Results Posted as of Aug 4, 2022