Clinical trial NCT01247324: A Study of Ocrelizumab in Comparison With Interferon Beta-1a (Rebif) in Participants With Relapsing Multiple Sclerosis
Official title: A Randomized, Double-Blind, Double-Dummy, Parallel-Group Study To Evaluate the Efficacy and Safety of Ocrelizumab in Comparison to Interferon Beta-1a (Rebif®) in Patients With Relapsing Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Relapsing Multiple Sclerosis
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2010-11-24
Enrollment: 821
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: This randomized, double-blind, double-dummy, parallel-group study will evaluate the efficacy and safety of ocrelizumab in comparison with interferon beta-1a (Rebif) in participants with relapsing multiple sclerosis. Participants will be randomized to receive either ocrelizumab 600 mg or matching placebo intravenous (IV) as 300 mg infusions on Days 1 and 15 for the first dose and as a single infusion of 600 mg for all subsequent infusions every 24 weeks, with placebo injections matching interferon beta-1a SC three times per week; or interferon beta-1a 44 mcg SC injections three times per week (with placebo infusions matching ocrelizumab infusions every 24 weeks). Planned duration of double-blind treatment is 96 weeks. Participants who complete the 96-week double-blind treatment will have an option to enter a single-group, active-treatment, open-label extension period, providing they fulfill the eligibility criteria.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of multiple sclerosis, in accordance with the revised McDonald criteria (2010)
* At least 2 documented clinical attacks within the last 2 years prior to screening or one clinical attack in the years prior to screening (but not within 30 days prior to screening)
* Neurologic stability for greater than or equal to (\>=) 30 days prior to both screening and baseline
* Expanded Disability Status Scale (EDSS) score 0 to 5.5 inclusive

Exclusion Criteria:

* Primary progressive multiple sclerosis
* Disease duration of more than 10 years in participants with EDSS less than or equal to (\<=) 2.0 at screening
* Contraindications for MRI
* Known presence of other neurological disorders which may mimic multiple sclerosis
* Pregnancy or lactation
* Requirement for chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
* History of or currently active primary or secondary immunodeficiency
* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
* Active infection, or history of or known presence of recurrent or chronic infection (e.g., hepatitis B or C, human immunodeficiency virus \[HIV\], syphilis, tuberculosis)
* History of progressive multifocal leukoencephalopathy
* Contraindications to or intolerance of oral or iv corticosteroids
* Contraindications to Rebif or incompatibility with Rebif use

Primary outcomes:
measure: Annualized Relapse Rate (ARR) in Participants With Relapsing Multiple Sclerosis (MS) at 96 Weeks
timeFrame: Week 96
Secondary outcomes:
measure: Time to Onset of Confirmed Disability Progression (CDP) for at Least 12 Weeks During the Double-Blind Treatment Period
timeFrame: Week 108
measure: Number of T1 Gadolinium (Gd)-Enhancing Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) During the Double-Blind Treatment
timeFrame: Baseline up to Week 96
measure: Number of New, and/or Enlarging T2 Hyperintense Lesions as Detected by Brain Magnetic Resonance Imaging (MRI) During the Double Blind Treatment
timeFrame: Baseline up to Week 96
measure: Percentage of Participants With Confirmed Disability Improvement (CDI) for at Least 12 Weeks
timeFrame: Week 96
measure: Time to Onset of Confirmed Disability Progression (CDP) for at Least 24 Weeks During the Double-Blind Treatment Period
timeFrame: Week 108
measure: Number of T1 Hypointense Lesions During the Double-Blind Treatment
timeFrame: Baseline up to Week 96
measure: Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score to Week 96
timeFrame: Baseline, Week 96
measure: Percent Change in Brain Volume as Detected by Brain Magnetic Resonance Imaging (MRI) From Week 24 to Week 96
timeFrame: From Week 24 up to Week 96
measure: Change From Baseline in Short Form Health Survey-36 (SF-36) Physical Component Summary (PCS) Score at Week 96
timeFrame: Baseline, Week 96
measure: Percentage of Participants Who Have No Evidence of Disease Activity (NEDA) up to Week 96
timeFrame: Week 96
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Baseline up to 588 weeks
measure: Exposure to Ocrelizumab (Area Under the Concentration - Time Curve, AUC)
timeFrame: Pre-infusion at Weeks 1, 24, 48, 72; and 30 minutes post-infusion at Week 72; at any time during Weeks 84 and 96
measure: Number of Participants With Anti-Drug Antibodies (ADAs) to Ocrelizumab
timeFrame: Baseline up to week 96
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: 21st Century Neurology
state: Arizona
city: Carmichael
country: United States
facility: Mercy Medical Group
state: California
city: La Jolla
country: United States
facility: Scripps Clinic
state: California
city: Laguna Hills
country: United States
facility: MS Center of California
state: California
city: Los Angeles
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Pasadena
country: United States
facility: Neuro-Therapeutics Inc.
state: California
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Melbourne
country: United States
facility: Health First Physicians Inc.
state: Florida
city: Miami
country: United States
facility: Mercy Research Institute
state: Florida
city: South Miami
country: United States
facility: Miami Research Associates
state: Florida
city: Tampa
country: United States
facility: Axiom Clinical Research of Florida
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Shepherd Center Inc.
state: Georgia
city: Atlanta
country: United States
facility: Emory University; Department of Neurology
state: Georgia
city: Atlanta
country: United States
facility: NeuroTrials Research, Inc.
state: Georgia
city: Chicago
country: United States
facility: Northwestern University; Dept. of Neurology
state: Illinois
city: Northbrook
country: United States
facility: Consultants in Neurology Ltd
state: Illinois
city: Avon
country: United States
facility: American Health Network Institute, LLC
state: Indiana
city: Boston
country: United States
facility: Massachusetts General Hospital.
state: Massachusetts
city: Clinton Township
country: United States
facility: Michigan Neurology Associates P.C.
state: Michigan
city: Farmington Hills
country: United States
facility: Michigan Institute for Neurological Disorders
state: Michigan
city: Golden Valley
country: United States
facility: The Minneapolis Clinic of Neurology
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University; Wash Uni. Sch. Of Med
state: Missouri
city: Saint Louis
country: United States
facility: The MS Center for Innovations In Care
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Albuquerque
country: United States
facility: University of New Mexico
state: New Mexico
city: Advance
country: United States
facility: The MS Center; Advance Neurology and Pain
state: North Carolina
city: Charlotte
country: United States
facility: Atrium Health Neurosciences Institute ? Charlotte
state: North Carolina
city: Charlotte
country: United States
facility: OnSite Clinical Solutions LLC
state: North Carolina
city: Hickory
country: United States
facility: Neurology Associates PA
state: North Carolina
city: Cincinnati
country: United States
facility: University Neurology Inc.
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Medical Research Foundation
state: Oklahoma
city: Portland
country: United States
facility: Providence Neurological Specialties
state: Oregon
city: Philadelphia
country: United States
facility: Albert Einstein Medical Center; Depatment of Neurosensory sciences
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Magee-Woman's Hospital
state: Pennsylvania
city: Houston
country: United States
facility: Uni of Texas Health Science Center At Houston
state: Texas
city: Lubbock
country: United States
facility: Bhupesh Dihenia M.D. P.A.
state: Texas
city: Burlington
country: United States
facility: Uni of Vermont Medical Center;
state: Vermont
city: Tacoma
country: United States
facility: Multicare Research Institute; Multicare Neuroscience Center of Washington
state: Washington
city: Buenos Aires
country: Argentina
facility: Instituto centenario
city: Ciudad Autonoma Bs As
country: Argentina
facility: Hospital Español
city: Rosario
country: Argentina
facility: Fundacion Rosarina de Neurorehabilitacion
city: St Leonards
country: Australia
facility: Royal North Shore Hospital; Department of Neurology
state: New South Wales
city: Linz
country: Austria
facility: Barmherzige Brueder Konventspital
city: Brugge
country: Belgium
facility: AZ Sint Jan
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc; Neurology
city: Roeselare
country: Belgium
facility: AZ Delta (Campus Rumbeke)
city: Goiania
country: Brazil
facility: Hospital das Clinicas - UFG;Reumatologia
state: GO
city: Porto Alegre
country: Brazil
facility: IMV Pesquisa Neurológica
state: RS
city: Joinville
country: Brazil
facility: Clinica Neurologica; Neurocirurgica de Joinville
state: SC
city: Pleven
country: Bulgaria
facility: MHAT Avis Medica; Neurology Department
city: Sofia
country: Bulgaria
facility: First MHAT; Clinic of Neurology
city: Sofia
country: Bulgaria
facility: MHATNP Sv.Naum EAD; Clinic in neurology diseases for movement disorders
city: Sofia
country: Bulgaria
facility: ACIBADEM CITY CLINIC TOKUDA HOSPITAL EAD; Clinic of Neurology and Sleep Medicine
city: Sofia
country: Bulgaria
facility: Military Medical Academy; Neurology
city: Valparaiso
country: Chile
facility: Hospital Carlos Van Buren
city: Brno
country: Czechia
facility: Fakultni nemocnice u sv. Anny; Neurologicka klinika
city: Hradec Kralove
country: Czechia
facility: Fakultni nemocnice Hradec Kralove
city: Jihlava
country: Czechia
facility: Nemocnice Jihlava; NEU-Neurologicke oddeleni
city: Pardubice
country: Czechia
facility: Krajska Nemocnice Pardubice Neurologicka Klinika
city: Prague
country: Czechia
facility: VFN Praha Poliklinika Rs Centrum - Budova A
city: Teplice
country: Czechia
facility: Krajska zdravotni, a. s. ? Nemocnice Teplice, o. z.; Neurologicke oddeleni
city: Tallinn
country: Estonia
facility: West Tallinn Central Hospital
city: Tartu
country: Estonia
facility: Tartu University Hospital
city: Tampere
country: Finland
facility: FinnMedi Oy
city: Bordeaux
country: France
facility: Groupe Hospitalier Pellegrin
city: Clermont Ferrand
country: France
facility: CHU Hopital Gabriel Montpied; Service de Neurologie
city: Nancy
country: France
facility: Hopital Central; Neurologie
city: Nimes
country: France
facility: CHU de Nîmes Hopital Caremeau; Service de Neurologie
city: Strasbourg
country: France
facility: Hopital Hautepierre - CHU Strasbourg; Service de Neurologie
city: Berlin
country: Germany
facility: Charité Universitaetsmedizin Berlin, Campus Charité Mitte
city: Dresden
country: Germany
facility: Universitätsklinikum "Carl Gustav Carus"; MS Center Dresden
city: Hamburg
country: Germany
facility: Asklepiosklinik Barmbek; Abteilung Neurologie
city: Hannover
country: Germany
facility: Diakoniekrankenhaus Henriettenstiftung gGMBH; Klinik für Neurologie und klinische Neurophysiologie
city: Mainz
country: Germany
facility: Universitaetsklinikum Mainz - PS; Klinik und Poliklinik fuer Neurologie
city: Oldenburg
country: Germany
facility: Praxis Dr. med. Mathias Niedhammer, Facharzt für Neurologie
city: Prien
country: Germany
facility: Neurozentrum Prien Elisabeth Hans-Thümmler Stefan Braune
city: Rostock
country: Germany
facility: Universitätsklinikum Rostock, Zentrum für Nervenheilkunde; Klinik und Poliklinik für Neurologie
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen, Zentrum für Neurologie
city: Westerstede
country: Germany
facility: Studienzentrum Nordwest Dr med Joachim Springub Herr Wolfgang Schwarz
city: Budapest
country: Hungary
facility: Semmelweis Egyetem AOK; Neurologiai Klinika
city: Budapest
country: Hungary
facility: Fovarosi Onkormanyzat Jahn Ferenc Del-Pesti
city: Tatabánya
country: Hungary
facility: Szent Borbala Korhaz; Neurology
city: Ramat-Gan
country: Israel
facility: Chaim Sheba Medical Center; Neurology Department
city: Roma
country: Italy
facility: Azienda Ospedaliera Sant'Andrea
state: Lazio
city: Milano
country: Italy
facility: Irccs Ospedale San Raffaele
state: Lombardia
city: Gallarate
country: Italy
facility: Azienda Socio Sanitaria Territoriale della Valle Olona (pres
state: Valle D?Aosta
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova; Clinica Neurologica
state: Veneto
city: Riga
country: Latvia
facility: Maritime Medicine Centre of Latvia Hospital of Vecmilgravis Department of Neurology
city: Riga
country: Latvia
facility: P. Stradins Clinical University Hospital; Neurology
city: Kaunas
country: Lithuania
facility: Kaunas Medical University Hospital
city: Klaipeda
country: Lithuania
facility: Klaipeda University Hospital Public Institution
city: Vilnius
country: Lithuania
facility: Vilnius University Hospital Santariskiu Clinic
city: Ciudad de México
country: Mexico
facility: Grupo Médico Camino S.C.
state: Mexico CITY (federal District)
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr Jose Eleuterio Gonzalez; Universidad Autónoma de Nuevo León
state: Nuevo LEON
city: Nieuwegein
country: Netherlands
facility: St. Antonius Ziekenhuis Nieuwegein
city: Callao
country: Peru
facility: Policlinico Especializado en Neurologia
city: Lima
country: Peru
facility: Clinica Anglo Americana
city: Lima
country: Peru
facility: Hospital Nacional Dos de Mayo
city: Pueblo Libre
country: Peru
facility: Clinica Centenario Peruano Japonesa; Neurology
city: Gdansk
country: Poland
facility: COPERNICUS Podmiot Leczniczy Sp. z o. o. Szpital im. M. Kopernika; Oddzia? Neurologiczny
city: Katowice
country: Poland
facility: Specjal. Praktyka Lekarska; Prof. Grzegorz Opala
city: Katowice
country: Poland
facility: MA-LEK Clinical Sp. Z o.o.
city: Plewiska
country: Poland
facility: Neurologiczny NZOZ Centrum Leczenia SM; Osrodek Badan Klinicznych
city: Braga
country: Portugal
facility: Hospital de Braga; Servico de Neurologia
city: Moskva
country: Russian Federation
facility: Central Clinical Hospital #2 N.A. Semashko OAO RJHD
state: Moskovskaja Oblast
city: Moskva
country: Russian Federation
facility: FGBU FNKC FMBA of Russia
state: Moskovskaja Oblast
city: Sankt-peterburg
country: Russian Federation
facility: St.-Peterburg State institution of health care City multifield hospital #2
state: Sankt Petersburg
city: St.Petersburg
country: Russian Federation
facility: MMA of Ministry of Defense of Russia named after S.M. Kirov
state: Sankt Petersburg
city: Yekaterinburg
country: Russian Federation
facility: Sverdlovsk Regional Clinical Hospital 1
state: Sverdlovsk
city: Tyumen
country: Russian Federation
facility: Regional Multiple Sclerosis Centre b/o CC ECM "Neftyanik"
state: Tjumen
city: Kemerovo
country: Russian Federation
facility: Kemerovo Regional Clinical Hospital
city: Novosibirsk
country: Russian Federation
facility: FSBIH Siberian Regional Medical Centre of FMBA of Russia
city: Novosibirsk
country: Russian Federation
facility: MRC for Oncology and Neurology Biotherapy
city: Samara
country: Russian Federation
facility: Samara State Medical University
city: Smolensk
country: Russian Federation
facility: Reg. SI of Health Care Smolensk Regional Clinical Hospital
city: Tyumen
country: Russian Federation
facility: Regional Multiple Sclerosis Centre b/o CC ECM "Neftyanik"
city: Belgrade
country: Serbia
facility: Military Medical Academy
city: Kragujevac
country: Serbia
facility: Clinical Center Kragujevac
city: NIS
country: Serbia
facility: Clinical Center Nis
city: Bratislava
country: Slovakia
facility: FNsP Bratislava - Nemocnica Stare mesto
city: Bratislava
country: Slovakia
facility: FNsP Bratislava, Nemocnica Ruzinov
city: Bratislava
country: Slovakia
facility: Univerzitna nemocnica Bratislava Nemocnica sv. Cyrila a Metoda; Nemocnicna lekaren
city: Zilina
country: Slovakia
facility: Fakultna nemocnica s poliklinikou Zilina
city: Durban
country: South Africa
facility: Dr CC Coetzee Inc
city: Santa Cruz De Tenerife
country: Spain
facility: Complejo Hospitalario Nuestra Señora de la Candelaria; Servicio de Neurologia
state: Tenerife
city: Bilbao
country: Spain
facility: Hospital de Basurto
state: Vizcaya
city: Madrid
country: Spain
facility: Hospital Universitario Puerta De Hierro Majadahonda; Servicio de Neurología
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Basel
country: Switzerland
facility: Universitätsspital Basel Medizin Neurologie; Neurologische Poliklinik
city: Lugano
country: Switzerland
facility: Ospedale Regionale Lugano Civico Medizin Neurologie; Neurologia
city: Mannouba
country: Tunisia
facility: Hopital Razi
city: Monastir
country: Tunisia
facility: Hopital Universitaire Fattouma Bourguiba
city: Tunis
country: Tunisia
facility: Hopital Charles Nicolle
city: Donetsk
country: Ukraine
facility: MMPIDon.Reg.Cl.&Ter.Med.Com.Neur.Dept.DNMU n.a.M.Gorkiy; Ch. of Nervous Diseases and Med. Genetics
city: Kharkov
country: Ukraine
facility: St.In.Inst. of Neurol.Psych.and Narcol.of the AMSU; Dept. of Neuroinfection and Multiply Sclerosis
city: Kyiv
country: Ukraine
facility: Kyiv City Cl.Hosp.#4 Depart.of Neurology #2NMU; Department of Neurology
city: Lviv
country: Ukraine
facility: Lviv Regional Clinical Hospital; Department of Neurology
city: Vinnytsya
country: Ukraine
facility: Vin.Reg.Psych.Hosp.N.A Yuschenko O.I., Vnmu N.A. Pyrogov; Department of Nervous Diseases
city: Liverpool
country: United Kingdom
facility: Walton Centre NHS Foundation Trust, Neuroscience Research Centre; CLINICAL TRIALS UNIT
city: London
country: United Kingdom
facility: Royal London Hospital; Neurology
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Arnold DL, Sprenger T, Bar-Or A, Wolinsky JS, Kappos L, Kolind S, Bonati U, Magon S, van Beek J, Koendgen H, Bortolami O, Bernasconi C, Gaetano L, Traboulsee A. Ocrelizumab reduces thalamic volume loss in patients with RMS and PPMS. Mult Scler. 2022 Oct;28(12):1927-1936. doi: 10.1177/13524585221097561. Epub 2022 Jun 7.
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citation: Giovannoni G, Kappos L, de Seze J, Hauser SL, Overell J, Koendgen H, Manfrini M, Wang Q, Wolinsky JS. Risk of requiring a walking aid after 6.5 years of ocrelizumab treatment in patients with relapsing multiple sclerosis: Data from the OPERA I and OPERA II trials. Eur J Neurol. 2022 Apr;29(4):1238-1242. doi: 10.1111/ene.14823. Epub 2021 May 5.
citation: Hauser SL, Kappos L, Arnold DL, Bar-Or A, Brochet B, Naismith RT, Traboulsee A, Wolinsky JS, Belachew S, Koendgen H, Levesque V, Manfrini M, Model F, Hubeaux S, Mehta L, Montalban X. Five years of ocrelizumab in relapsing multiple sclerosis: OPERA studies open-label extension. Neurology. 2020 Sep 29;95(13):e1854-e1867. doi: 10.1212/WNL.0000000000010376. Epub 2020 Jul 20.
citation: Kappos L, Wolinsky JS, Giovannoni G, Arnold DL, Wang Q, Bernasconi C, Model F, Koendgen H, Manfrini M, Belachew S, Hauser SL. Contribution of Relapse-Independent Progression vs Relapse-Associated Worsening to Overall Confirmed Disability Accumulation in Typical Relapsing Multiple Sclerosis in a Pooled Analysis of 2 Randomized Clinical Trials. JAMA Neurol. 2020 Sep 1;77(9):1132-1140. doi: 10.1001/jamaneurol.2020.1568.
citation: Hauser SL, Bar-Or A, Comi G, Giovannoni G, Hartung HP, Hemmer B, Lublin F, Montalban X, Rammohan KW, Selmaj K, Traboulsee A, Wolinsky JS, Arnold DL, Klingelschmitt G, Masterman D, Fontoura P, Belachew S, Chin P, Mairon N, Garren H, Kappos L; OPERA I and OPERA II Clinical Investigators. Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis. N Engl J Med. 2017 Jan 19;376(3):221-234. doi: 10.1056/NEJMoa1601277. Epub 2016 Dec 21.