Relapsing Multiple Sclerosis Clinical Trial
— FENhance 2Official 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
Verified date | April 2024 |
Source | Hoffmann-La Roche |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Active, not recruiting |
Enrollment | 751 |
Est. completion date | November 27, 2025 |
Est. primary completion date | October 2, 2025 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 55 Years |
Eligibility | 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 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. - 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 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. |
Country | Name | City | State |
---|---|---|---|
Austria | Kepler Universitätskliniken GmbH - Med Campus III; Neurologie & Psychiatrie | Linz | |
Austria | Medizinische Universität Wien; Univ.Klinik fuer Neurologie | Wien | |
Brazil | Santa Casa de Misericordia; de Belo Horizonte | Belo Horizonte | MG |
Brazil | L2 Ip Instituto de Pesquisas Clinicas Ltda ME; Centro Medico Hospitalar | Brasilia | DF |
Brazil | Instituto de Neurologia de Curitiba | Curitiba | PR |
Brazil | Clinica Neurologica; Neurocirurgica de Joinville | Joinville | SC |
Brazil | Hospital Sao Lucas - PUCRS | Porto Alegre | RS |
Brazil | IMV Pesquisa Neurológica | Porto Alegre | RS |
Brazil | Núcleo de Pesquisa do Rio Grande do Sul | Porto Alegre | RS |
Brazil | Praxis Pesquisa Médica | Santo Andre | SP |
Brazil | CEMEC - Centro Multidisciplinar de Estudos Clínicos | Sao Bernardo Do Campo | SP |
Brazil | Centro de Pesquisas Clinicas; CPCLIN | Sao Paulo | SP |
Brazil | Hospital Santa Marcelina; AME - Ambulatório de Especialidades Médicas | Sao Paulo | SP |
Brazil | Jordy Sinapse Medicina LTDA ME | Sao Paulo | SP |
Bulgaria | UMHAT Dr. Georgi Stranski; 2nd Neurology Clinic, Occupational Diseases | Pleven | |
Bulgaria | MHATNP Sveti Naum EAD | Sofia | |
Canada | CIUSSS du Saguenay Lac-Saint-Jean, Chicoutimi Hospital | Chicoutimi | Quebec |
Canada | University of Alberta Hospital | Edmonton | Alberta |
Canada | Recherche Sepmus Inc. | Greenfield Park | Quebec |
Canada | MUCH - Montreal Neurological Institute & Hospital | Montreal | Quebec |
Canada | The Ottawa Hospital - General Campus; Department of Neurology - Multiple Sclerosis | Ottawa | Ontario |
Canada | CHU de Québec | Quebec City | Quebec |
Denmark | Hjerne- og nervesygdomme, Ambulatorium, Skleroseklinikken | Aabenraa | |
Denmark | Sydvestjysk Sygehus Esbjerg; Neurologisk Afd., Skleroseklinikken | Esbjerg | |
France | Hopital Gabriel Montpied CHU de Clermont-Ferrand; Service de Neurologie B | Clermont-Ferrand | |
France | Hôpital Pasteur; Service de Neurologie | Nice | |
France | Hôpital Charles Nicolle; Service de Neurologie | Rouen | |
France | CHU toulouse - Hôpital Purpan; Departement de Neurologie | Toulouse | |
Greece | University General Hospital of Ioannina; Neurology Clinic | ??a????a | |
Greece | Hospital Eginition; First Department of Neurology | Athens | |
Greece | University General Hospital of Larisa; Neurology Clinic | Larisa | |
Greece | AHEPA Univ. General Hospital of Thessaloniki; B' Neurology Dept. | Thessaloniki | |
Guatemala | Nucare | Ciudad Guatemala | |
India | Zydus Hospital; Department of Neuro Sciences | Ahmadabad CITY | Gujarat |
India | Postgraduate Institute of Medical Education and Research | Chandigarh | |
India | Christian Medical College and Hospital | Ludhiana | Punjab |
India | Seth G.S Medical College K.E.M Hospital | Mumbai | Maharashtra |
India | Max Super Speciality Hospital | New Delhi | Delhi |
India | Sir Gangaram Hospital | NEW Delhi Delhi | Delhi |
India | Deenanath Mangeshkar Hospital & Research Centre | Pune | Maharashtra |
India | Sahyadri Superspeciality Hospital | Pune City | Maharashtra |
India | SRM Institute of Medical Sciences | Vadapalani | Tamil NADU |
Italy | Azienda Ospedaliero-Universitaria Consorziale Pol. di Bari; Neuroscienze e Organi di Senso | Bari | Puglia |
Italy | Ospedale Binaghi; Centro Sclerosi Multipla | Cagliari | Sardegna |
Italy | Universita? G. D'Annunzio; Dipartimento di Neuroscienze, Imaging e Scienze Cliniche | Chieti | Abruzzo |
Italy | Irccs A.O.U.San Martino Ist; Dinogmi | Genova | Liguria |
Italy | Fond. Istituto Neurologico C.Besta; UO Neurologia IV - Neuroimmunologia Malattie Neuromuscolari | Milano | Lombardia |
Italy | Ospedale Civile di Montichiari; Centro Sclerosi Multipla | Montichiari | Lombardia |
Italy | A. O. U. Federico II; Dip Neuroscienze, Scienze Riproduttive ed Odontostomatologiche | Napoli | Campania |
Italy | AOU Policlinico Giaccone; UOC Neurologia e Neurofisiopatologia-Amb Sclerosi Multipla | Palermo | Sicilia |
Italy | IRCCS Istituto Neurologico C. Mondino?Dip. Neurologia Neuroriabilitazione S.S. Sclerosi Multipla | Pavia | Lombardia |
Italy | IRCCS Istituto Neurologico Neuromed; Centro per lo Studio e la Cura della Sclerosi Multipla | Pozzilli | Molise |
Italy | NCL Institute Neuroscience | Roma | Lazio |
Italy | Ospedale S.Camillo Forlanini; UOSD Day Hospital Neurologico e Neurochirurgico | Roma | Lazio |
Italy | Policlinico Universitario A. Gemelli; UOC Neurologia - Centro Sclerosi Multipla | Roma | Lazio |
Korea, Republic of | Keimyung University Dongsan Medical Center | Daegu | |
Korea, Republic of | National Cancer Center | Goyang-si | |
Korea, Republic of | Samsung Medical Center | Seoul | |
Korea, Republic of | Seoul National University Hospital | Seoul | |
Mexico | Unidad de Investigación en Salud; Psiquiatria | Chihuahua | |
Mexico | Grupo Médico Camino S.C. | Ciudad de México | Mexico CITY (federal District) |
Mexico | Mexico Centre for Clinical Research | Ciudad de México | Mexico CITY (federal District) |
Mexico | Unidad de investigacion en salud (UIS); Neurociencias | Ciudad de México | |
Mexico | Clinstile S.A de C.V. | Mexico City | Mexico CITY (federal District) |
Poland | Neurocentrum Bydgoszcz sp. z o.o | Bydgoszcz | |
Poland | NZOZ Vitamed | Bydgoszcz | |
Poland | COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika; Oddzia? Neurologiczny | Gdansk | |
Poland | RESMEDICA Spolka z o.o. | Kielce | |
Poland | Centrum Neurologii Klinicznej | Krakow | |
Poland | Malopolskie Centrum Diagnostyczne MEDICAL Sp. z o. o. | Krakow | |
Poland | Centrum Neurologii Krzysztof Selmaj | Lodz | |
Poland | Instytut Zdrowia Dr Boczarska-Jedynak Sp. z o.o. Sp. k. | Oswiecim | |
Poland | Neurologiczny Niepubliczny ZOZ Centrum Leczenia SM Osrodek Bada? Klinicznych | Plewiska | |
Poland | NZOZ NEURO-KARD Ilkowski i Partnerzy Sp. Partn. Lek | Pozna? | |
Poland | MedPolonia | Poznan | |
Poland | Wojewódzki Szpital Specjalistyczny Nr 3 | Rybnik | |
Poland | Klinika Neurologii I Wydzialu Lekarskiego WUM w Warszawie | Warszawa | |
Poland | Wro Medica | Wroc?aw | |
Poland | IBISMED Wielospecjalistyczne Centrum Medyczne | Zabrze | |
Russian Federation | Regional clinical hospital named after prof. S.V. Ochapovsky | Krasnodar | |
Russian Federation | FSBHI Siberian Clinical Center of the Federal Medical and Biological Agency | Krasnoyarsk | Krasnojarsk |
Russian Federation | Krasnoyarsk State Medical Academy | Krasnoyarsk | Krasnojarsk |
Russian Federation | Federal center of brain research and neurotechnologies | Moskva | Moskovskaja Oblast |
Russian Federation | Regional Clinical Hospital N.A. Semashko; Neurology | Nizhny Novgorod | Niznij Novgorod |
Russian Federation | State Novosibirsk Regional Clinical Hospital | Novosibirsk | |
Russian Federation | National Center of Social Significant Disease | Sankt-peterburg | Leningrad |
Russian Federation | Nebbiolo Center for Clinical Trials | Tomsk | |
Turkey | Gazi University Medical Faculty; Departmant of Norology | Ankara | |
Turkey | Hacettepe University Medical Faculty; Neurology | Ankara | |
Turkey | Baskent Universitesi Ankara Hastanesi; Noroloji Bolumu | Çankaya | |
Turkey | Bakirkoy State Mental Hospital | Istanbul | |
Turkey | Istanbul Universitesi - Cerrahpasa Cerrahpasa Tip Fakultesi; Noroloji Anabilim Dali | Istanbul | |
Turkey | Sancaktepe Training and Research Hospital; Neurology | Istanbul | |
Turkey | Selcuk University Medical Faculty; Norology department | Istanbul | |
Turkey | Kocaeli University Hospital; Department of Neurology | Kocaeli | |
Turkey | Ege Üniversitesi Tip Fakültesi | Lzmir | |
Turkey | Mersin University Medical Faculty; Neurology | Mersin | |
Turkey | Ondokuz Mayis University School of Medicine; Neurology | Samsun | |
Turkey | Karadeniz Tecnical Uni. Med. Fac.; Neurology | Trabzon | |
Turkey | Van Yuzuncu Yil University Hospital; Neurology | Van | |
United Kingdom | Salford Royal NHS Foundation Trust | Salford | |
United Kingdom | Recognition Health | Winchester | |
United States | American Health Network Institute, LLC | Avon | Indiana |
United States | University of Cincinnati; Department of Neurology | Cincinnati | Ohio |
United States | North Central Neurology Associates | Cullman | Alabama |
United States | Wayne State University; Department of Neurology | Detroit | Michigan |
United States | Integrated Neurology Services PLLC | Falls Church | Virginia |
United States | Neuro Institute of New England P.C.; Research | Foxboro | Massachusetts |
United States | University of Kansas Medical Center | Kansas City | Kansas |
United States | Hope Neurology | Knoxville | Tennessee |
United States | Medical College of Wisconsin, Inc. | Milwaukee | Wisconsin |
United States | Xenoscience | Phoenix | Arizona |
United States | KI Health Partners, LLC; New England Institute for Clinical Research | Stamford | Connecticut |
United States | Stanford University Medical Center; Stanford Neuroscience Health Center | Stanford | California |
United States | University of South Florida | Tampa | Florida |
United States | Los Angeles Biomedical Research Institute at Harbor-UCLA | Torrance | California |
United States | Georgetown University Medical Center | Washington | District of Columbia |
Lead Sponsor | Collaborator |
---|---|
Hoffmann-La Roche |
United States, Austria, Brazil, Bulgaria, Canada, Denmark, France, Greece, Guatemala, India, Italy, Korea, Republic of, Mexico, Poland, Russian Federation, Turkey, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Annualized Relapse Rate (ARR) | Minimum of 96 weeks | ||
Secondary | Time to Onset of Composite 12-week Confirmed Disability Progression (cCDP12) | Minimum of 96 weeks | ||
Secondary | Time to Onset of Composite 24-week Confirmed Disability Progression (cCDP24) | Minimum of 96 weeks | ||
Secondary | Time to Onset of 12-week Confirmed Disability Progression (CDP12) | Minimum of 96 weeks | ||
Secondary | Time to Onset of 24-week Confirmed Disability Progression (CDP24) | Minimum of 96 weeks | ||
Secondary | Total Number of T1 Gadolinium-enhancing (Gd+) Lesions, New and/or Enlarging T2-weighted Lesions as Detected by Magnetic Resonance Imaging (MRI) | Baseline, Weeks 12, 24, 48 and 96 | ||
Secondary | Percentage Change in Total Brain Volume from Week 24 as Assessed by MRI | From Week 24 to Week 96 | ||
Secondary | Change in Participant-Reported Physical Impacts of Multiple Sclerosis (MS) Measured by the Multiple Sclerosis, 29-Item [MSIS-29] Physical Scale | The MSIS-29, version 2 is a 29-item patient-reported measure of the physical and psychological impacts of MS. Participants are asked to rate how much their functioning and well-being has been impacted over the past 14 days on a 4-point scale, from "Not at all" (1) to "Extremely" (4). The physical score is the sum of items 1-20, which is then transformed to a 0-100 scale. The psychological score is the sum of items 21-29, transformed to a 0-100 scale. Higher scores indicate a greater impact of MS. | Baseline, Weeks 12, 24, 36, 48, 60, 72, 84 and 96 | |
Secondary | Time to Onset of 12-week Confirmed 4-point Worsening in Symbol Digit Modality Test (SDMT) Score | The SDMT is used for detecting the presence of cognitive impairment and changes in cognitive functioning over time and in response to treatment. The SDMT is brief, is easy to administer test, and involves a simple substitution task. Using a reference key, the examinee has 90 seconds to pair specific numbers with given geometric figures. Responses will be collected only orally, and administration time is approximately 5 minutes. The number of correct responses in 90 seconds will be considered the SDMT score. A decrease by 4 points on the SDMT score from baseline represents a clinically meaningful change in cognitive processing. The SDMT score ranges from 0 to 110. The higher the results, the better processing speed/working memory. | Minimum of 96 weeks | |
Secondary | Change from Baseline to Week 48 in the Concentration of Serum Neurofilament Light chain (NfL) | Up to 48 weeks | ||
Secondary | Percentage of Participants with Adverse Events (AEs) | Up to 4.5 years | ||
Secondary | Plasma Concentrations of Fenebrutinib at Specified Timepoints | Up to 4.5 years |
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