FENhance: A 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: NCT04586010
• Collaborator: (none)
• Enrollment: 736
• Locations: 126
• Arms: 2
• Anticipated Duration (Months): 56.4
• Patients Per Site: 5.8
• Patients Per Site Per Month: 0.1

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
Relapsing Multiple Sclerosis	Drug: fenebrutinib; Drug: teriflunomide; Drug: placebo	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 17, 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 several 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	Center for Neurology and Spine - Phoenix - Hunt - PPDS	Phoenix	Arizona	United States	85032
2	North County Neurology Associates	Carlsbad	California	United States	92011
3	University of California Irvine	Irvine	California	United States	92697
4	SC3 Research Group, Inc	Pasadena	California	United States	91105
5	University of Colorado Denver	Aurora	Colorado	United States	80045
6	Mountain Neurological Research Center; Roaring Fork Neurologt, P.C.	Basalt	Colorado	United States	81621
7	Mountain View Clinical Research	Denver	Colorado	United States	80209
8	Advanced Neurology of Colorado, LLC	Fort Collins	Colorado	United States	80528
9	Neurology Associates, PA; Research Department	Maitland	Florida	United States	32751
10	Elite Clinical Research	Miami	Florida	United States	33144
11	Axiom Clinical Research of Florida	Tampa	Florida	United States	33609
12	NorthShore University HealthSystem	Highland Park	Illinois	United States	60035
13	Fort Wayne Neurological Center	Fort Wayne	Indiana	United States	46805
14	The NeuroMedical Center	Baton Rouge	Louisiana	United States	70810
15	University of Massachusetts Medical School	Worcester	Massachusetts	United States	01655
16	Henry Ford Health System	Detroit	Michigan	United States	48202
17	Rutgers New Jersey Medical School	Newark	New Jersey	United States	07103
18	St. Lawrence Health System	Potsdam	New York	United States	13676-1786
19	Miami Valley Hospital South; Dayton Physician's Office	Centerville	Ohio	United States	45459
20	The Boster Center for MS	Columbus	Ohio	United States	43235
21	Oklahoma Medical Research Foundation; MS Center of Excellence	Oklahoma City	Oklahoma	United States	73104
22	St. Luke's University Health network	Bethlehem	Pennsylvania	United States	18015
23	Premier Neurology	Greer	South Carolina	United States	29650
24	Neurology Clinic PC	Cordova	Tennessee	United States	38018
25	New Orleans Center for Clinical Research	Knoxville	Tennessee	United States	37920
26	Texas Institute for Neurological Disorders	Sherman	Texas	United States	75092
27	Blacksburg Neurology, PC	Christiansburg	Virginia	United States	24073
28	Multiple Sclerosis Center of Greater Washington	Vienna	Virginia	United States	22182
29	MultiCare Health System Institute for Research and Innovation	Tacoma	Washington	United States	98405
30	Wheaton Franciscan Healthcare - St. Francis Outpatient Center; Center for Neurological Disorders	Milwaukee	Wisconsin	United States	53215
31	IME - Instituto Médico Especializado; Ensayos Clínicos	Buenos Aires		Argentina	C1405BCH
32	Instituto de Investigaciones Metabolicas (Idim)	Ciudad Autonoma de Buenos Aires		Argentina	C1012AAR
33	Instituto DIABAID	Ciudad Autónoma de Buenos Aires		Argentina	C1061ABD
34	Centro de Investigaciones Médicas Tucuman; REUMATHOLOGY	San Miguel		Argentina	T4000AXL
35	Peking University First Hospital	Beijing City		China	100034
36	the First Hospital of Jilin University	Changchun		China	130021
37	Xiangya Hospital Central South University	Changsha City		China	410008
38	West China Hospital, Sichuan University	Chengdu		China	610041
39	The First Affiliated Hospital, Chongqing Medical University	Chongqing		China	400016
40	The First Affiliated Hospital of Sun Yat-sen University	Guangzhou City		China	510080
41	The affiliated Hospital of Guiyang Medical College	Guiyang		China
42	The Second Hospital of Hebei Medical University	Shijiazhuang		China	050000
43	The First Affiliated Hospital of Soochow University; Neurology department	Soochow		China	215000
44	Tianjin Medical University General Hospital	Tianjin		China	300052
45	Tongji Hospital Tongji Medical College Huazhong University of Science and Technology	Wuhan City		China	430030
46	Tangdu Hospital, The Fourth Military Medical University; Neurology Department	Xi'an City		China	710038
47	Helsinki University Central Hospital; Department of Neurology	Helsinki		Finland	00290
48	Terveystalo Oulu	Oulu		Finland	90100
49	Jüdisches Krankenhaus Berlin; Abteilung fur Neurologie	Berlin		Germany	13347
50	Studienzentrum für Neurologie und Psychiatrie	Böblingen		Germany	71034
51	Universitätsklinikum "Carl Gustav Carus", Zentrum für Klinische Neurowissenschaften	Dresden		Germany	01307
52	Universitätsklinikum Gießen und Marburg GmbH; Neurologie	Gießen		Germany	35392
53	Uniklinik Schleswig-Holstein; Neuroimmunologie, Institut für Klinische Chemie + Klinik f. Neurologie	Kiel		Germany	24105
54	Universitätsklinikum Münster; Klinik und Poliklinik für Neurologie	Münster		Germany	48149
55	Nordwest-Krankenhaus Sanderbusch gGMBH; Neurologische Klinik	Sande		Germany	26452
56	Praxis Dr. med. Andreas Kowalik, Arzt für Neurologie und Psychiatrie	Stuttgart		Germany	70174
57	Universitätsklinikum Tübingen, Zentrum für Neurologie	Tübingen		Germany	72076
58	Universitätsklinikum Ulm; Klinik für Neurologie	Ulm		Germany	89081
59	Studienzentrum Nordwest, Dr. med. Joachim Springub / Herr Wolfgang Schwarz	Westerstede		Germany	26655
60	Pamela Youde Nethersole Eastern Hospital; Department of Medicine	Hong Kong		Hong Kong
61	Queen Mary Hospital; Department of Medicine, Division of Neurology	Hong Kong		Hong Kong
62	Prince of Wales Hospital; Division of Neurology, Department of Medicine and Therapeutics	Shatin, New Territories		Hong Kong
63	Clinexpert Kft.	Budapest		Hungary	1033
64	Dr. HIBBEY Egeszsegugyi es Szolgaltato Kft	Tatabánya		Hungary	2800
65	Ospedale San Salvatore; Clinica Neurologica - Centro Sclerosi Multipla	L'Aquila	Abruzzo	Italy	67100
66	AOU Seconda Università degli Studi; Dip. Assistenziale Integrato Medicina Int-II Clinica Neurologica	Napoli	Campania	Italy	80131
67	AOU Policlinico - Università L. Vanvitelli; D.A.I. di Medicina Interna e Specialistica	Napoli	Campania	Italy	80138
68	A.O.U. di Parma; SC Neurologia, Amb. Sclerosi Multipla (malattie demielinizzanti)	Parma	Emilia-Romagna	Italy	43126
69	Policlinico Tor Vergata Dip. Neuroscienze-Clinica Neurologica-UOSD Sclerosi Multipla	Roma	Lazio	Italy	00133
70	Policlinico Umberto I; Centro Sclerosi Multipla DAI Neuroscienze e Salute Mentale	Roma	Lazio	Italy	00185
71	Azienda Ospedaliera Sant'Andrea; UOC Neurologia	Roma	Lazio	Italy	00189
72	ASST PAPA GIOVANNI XXIII Neurologia USS Malattie Autoimmuni Centro Sclerosi Multipla	Bergamo	Lombardia	Italy	24127
73	Ospedale S.Antonio Abate; Neurologia 2 - Sclerosi Multipla e Recupero Neurologico	Gallarate	Lombardia	Italy	21013
74	IRCCS Ospedale San Raffaele; Neurologia Neurofisiologia Neuroriabilitazione-Centro Sclerosi Multipla	Milano	Lombardia	Italy	20132
75	Azienda Ospedaliero Universitaria Ospedali Riuniti Umberto I-G.M. Lancisi-G. Salesi Di Ancona	Torrette - Ancona	Marche	Italy	60100
76	Ospedale Regina Montis Regalis; SC Neurologia, Centro Sclerosi Multipla	Mondovì (CN)	Piemonte	Italy	12084
77	AOUC Azienda Ospedaliero-Universitaria Careggi; Neurologia 2	Firenze	Toscana	Italy	50134
78	AOU Senese - Presidio Ospedaliero Le Scotte; UOSA Neurologia Sperimentale	Siena	Toscana	Italy	53100
79	Azienda Ospedaliera di Padova; Clinica Neurologica	Padova	Veneto	Italy	35128
80	Zuyderland Medisch Centrum - Sittard Geleen	Sittard-Geleen		Netherlands	6162 BG
81	Hospital IV Alberto Sabogal Sologuren; Unidad de Investigacion	Bellavista		Peru	Callao 2
82	HOSPITAL NACIONAL GUILLERMO ALMENARA IRIGOYEN; Unidad de Investigacion en Neurologia	La Victoria, Lima		Peru	Lima 13
83	Hospital Nacional Dos de Mayo; Unidad de Investigacion de Neurologia	Lima		Peru	15003
84	Clinica Internacional Sede Lima	LIma		Peru	Lima 01
85	ASOCIACION CIVIL PORLASALUD; Unidad de Investigación	Miraflores		Peru	15046
86	Clinica Centenario Peruano Japonesa; Neurology	Pueblo Libre		Peru	Lima 21
87	Hospital de Braga; Centro Clínico Académico (Piso 1, Ala E)	Braga		Portugal	4710-243
88	HUC; Servico de Neurologia	Coimbra		Portugal	3000-075
89	Hospital Santo Antonio dos Capuchos; Servico de Neurologia	Lisboa		Portugal	1169-050
90	Hospital de Santa Maria; Servico de Neurologia	Lisboa		Portugal	1649-035
91	Hospital Beatriz Angelo; Servico de Neurologia	Loures		Portugal	2674-514
92	Hospital Geral de Santo Antonio; Servico de Neurologia	Porto		Portugal	4099-001
93	Centro Hospitalar Entre o Douro e Vouga E.P.E. - Hospital de São Sebastião; Servilo de Neurologia	Santa Maria Da Feira		Portugal	4520-211
94	Regional State Budgetary Institution of Healthcare "Regional Clinical Hospital"	Barnaul	Altaj	Russian Federation	656024
95	N.P. Bechtereva Institute of the Human Brain	Sankt-petersburg	Sankt Petersburg	Russian Federation	197376
96	Ulyanovsk Regional Clinical Hospital	Ulyanovsk	Uljanovsk	Russian Federation	432063
97	SHI Sverdlovsk Regional Clinical Hospital #1;Neurology	Ekaterinburg		Russian Federation	620102
98	Center of Cardiology and Neurology	Kirov		Russian Federation	610007
99	Siberian Regional Medical Centre; Centre of Multiple Sclerosis	Novosibirsk		Russian Federation	630007
100	Leningrad Regional Clinical Hospital	St Petersburg		Russian Federation	194291
101	Pavlov State Medical Uni ; Neurology	St Petersburg		Russian Federation	197022
102	Republican clinical hospital named after G.G. Kuvatov	UFA		Russian Federation	450005
103	Hospital Universitari de Bellvitge; Servicio de Neurologia	L'Hospitalet de Llobregat	Barcelona	Spain	08907
104	Hospital Quiron de Madrid; Servicio de Neurologia	Pozuelo de Alarcon	Madrid	Spain	28223
105	Hospital Universitario Virgen de Arrixaca; Servicio de Neurología	EL Palmar (EL Palmar)	Murcia	Spain	30120
106	Hospital Alvaro Cunqueiro; Servicio de Neurologia	Vigo	Pontevedra	Spain
107	Hospital Universitari Vall d'Hebron; Servicio de Neumo-Inmunologia	Barcelona		Spain	08035
108	Hospital Ramon y Cajal; Servicio de Neurologia	Madrid		Spain	28034
109	Hospital Universitario Virgen Macarena; Servicio de Neurologia	Sevilla		Spain	41009
110	Inselspital Bern Medizin Neurologie; Neurologische Poliklinik	Bern		Switzerland	3010
111	Ospedale Regionale di Lugano - Civico; Neurologia	Lugano		Switzerland	6903
112	China Medical University Hospital; Neurology	North Dist.		Taiwan	40447
113	National Taiwan University Hospital; Neurology	Taipei		Taiwan	100
114	Chang Gung Memorial Foundation - Linkou - Neurology	Taoyuan		Taiwan	333
115	Medical Center Dopomoga Plus	Kyiv	Chernihiv Governorate	Ukraine	02123
116	MNE Lviv Territorial Medical Association Clinical Hospital for Palliative Care	Lviv	Chernihiv Governorate	Ukraine	79007
117	Municipal Institution Dnipropetrovsk Regional Clinical Hospital n a I I Mechnykov; Neurology dept #1	Dnipro	Katerynoslav Governorate	Ukraine	49005
118	Municipal Non-profit Enterprise Zaporizhzhya Regional Hospital Zaporizhzhya Regional Council	Zaporizhzhia	Katerynoslav Governorate	Ukraine	69600
119	Zaporizhia City Multispecialty Clinical Hospital #9	Zaporizhzhye	Katerynoslav Governorate	Ukraine	69063
120	Medical Center of Private Execution First Private Clinic	Kyiv	KIEV Governorate	Ukraine	03037
121	Salutem Medical Center	Vinnytsia	KIEV Governorate	Ukraine	21050
122	Medical Clinical Research Center of Medical Center LLC Health Clinic	Vinnytsia	Podolia Governorate	Ukraine	21009
123	Miska Klinichna Likarnia №16	Dnipropetrovsk	Tavria Okruha	Ukraine	49100
124	Ams of Ukraine; Inst. of Neurology, Psychiatry & Narcology	Kharkov		Ukraine	61068
125	Lviv Regional Clinical Hospital; Department of Neurology	Lviv		Ukraine	79010
126	Odesa Regional Clinical Hospital; Neurosurgery Department	Odesa		Ukraine	65117

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: NCT04586010
• Other Study ID Numbers: GN41851; 2019-004857-10
• 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