A Study of the Efficacy and Safety of Ocrelizumab in Patients With Relapsing-Remitting Multiple Sclerosis
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Interventions
- Registration Number
- NCT00676715
- Lead Sponsor
- Genentech, Inc.
- Brief Summary
This is a phase II, multicenter, randomized, parallel-group, partially blinded, placebo and Avonex (interferon beta-1a) controlled dose finding study to evaluate the efficacy as measured by brain MRI lesions, and safety of 2 dose regimens of ocrelizumab in participants with Relapsing Remitting Multiple Sclerosis (RRMS).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 220
- Ability to provide written informed consent and to be compliant with the schedule of protocol assessments
- Relapsing-remitting multiple sclerosis (MS)
- Ages 18-55 years inclusive
- For sexually active female and male participants of reproductive potential, use of reliable means of contraception
- Secondary or primary progressive multiple sclerosis at screening
- Incompatibility with MRI
- Contra-indications to or intolerance of oral or IV corticosteroids
- Known presence of other neurologic disorders
- Pregnancy or lactation
- Lack of peripheral venous access
- History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
- Significant, uncontrolled disease, such as cardiovascular, pulmonary, renal, hepatic, endocrine or gastrointestinal
- Congestive heart failure
- Known active bacterial, viral, fungal, mycobacterial infection or other infection or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks prior to screening or oral antibiotics within 2 weeks prior to screening
- History or known presence of recurrent or chronic infection
- History of cancer, including solid tumors and hematological malignancies (except basal cell, in situ squamous cell carcinomas of the skin, and in situ carcinoma of the cervix of the uterus that have been excised and resolved)
- History of alcohol or drug abuse within 24 weeks prior to randomization
- History of or currently active primary or secondary immunodeficiency
- History of coagulation disorders
- Treatment with any investigational agent within 4 weeks of screening
- Receipt of a live vaccine within 6 weeks prior to randomization
- Incompatibility with Avonex use
- Previous treatment with rituximab
- Previous treatment with lymphocyte-depleting therapies except mitoxantrone
- Treatment with lymphocyte trafficking blockers within 24 weeks prior to randomization
- Treatment with beta interferons, glatiramer acetate, IV immunoglobulin, plasmapheresis, or immunosuppressive therapies within 12 weeks prior to randomization
- Systemic corticosteroid therapy within 4 weeks prior to randomization
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Participants received two intravenous (IV) infusions of matching placebo separated by 14 days in Cycle 1, followed by two infusions of ocrelizumab 300 mg separated by 14 days in cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of cycles 3 and 4. Each cycle was of 168 days. Ocrelizumab 1000 mg Ocrelizumab Participants received two IV infusions of ocrelizumab 1000 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 1000 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 1000 mg was administered on Day 1 of Cycle 3 and a single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycle 4. Each cycle was of 168 days. Avonex Avonex Participants received weekly intramuscular injections of Avonex 30 microgram (mcg) in Cycle 1, followed by two infusions of OCR 300 mg separated by 14 days in Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days. Ocrelizumab 600 mg Ocrelizumab Participants two IV infusions of ocrelizumab 300 mg separated by 14 days in Cycle 1, followed by an infusion of ocrelizumab 600 mg on Day 1 and an infusion of placebo on Day 15 of Cycle 2. A single infusion of ocrelizumab 600 mg was administered on Day 1 of Cycles 3 and 4. Each cycle was of 168 days.
- Primary Outcome Measures
Name Time Method Total Number of Gadolinium-Enhancing T1 Lesions Observed on Magnetic Resonance Imaging (MRI) Scans of the Brain Week 12 to Week 24 Mean of total number of gadolinium-enhancing T1 lesions observed on MRI scans of the brain at Weeks 12, 16, 20, 24 was determined using average imputation method.
- Secondary Outcome Measures
Name Time Method Annualized Protocol Defined Relapse Rate at Week 24 Week 24 Adjusted annualized relapse rate for geographical region is reported here. The relapse rate was calculated as the total number of relapses for each participant divided by the total number of patient-years.
Percentage of Participants Who Remained Relapse Free at Week 24 Week 24 Percentage of participants who remained relapse free at week 24 were reported. Percentages have been rounded off to the first decimal.
Change From Baseline in Total Volume of T2 Lesions on MRI Scans of the Brain at Week 24 Baseline, Week 24 Change from baseline in total volume of T2 lesions on MRI scans of the brain at Week 24 was reported.
Total Number of New Gadolinium-Enhancing T1 Lesions Observed by MRI Scans of the Brain Weeks 4 to Week 24 Total number of new gadolinium-enhancing T1 lesions observed by MRI scans of the brain were reported.
Total Number of Gadolinium-Enhancing T1 Lesions Weeks 4 to Week 24 Total number of gadolinium-enhancing T1 lesions from Week 4 to Week 24 were reported.
Trial Locations
- Locations (84)
Phoenix Neurological Associates Ltd
🇺🇸Phoenix, Arizona, United States
CCB Medical institute, Ministry of Interior Sofia; CLINIC OF NEUROLOGY
🇧🇬Sofia, Bulgaria
MS Center of Vero Beach
🇺🇸Vero Beach, Florida, United States
Columbia University Medical Center; The Neurological Institute of New York
🇺🇸New York, New York, United States
Fakultna Nemocnica Nitra; Neurologicka Klinika
🇸🇰Nitra, Slovakia
Vin.Reg.Psych.Hosp.N.A Yuschenko O.I., Vnmu N.A. Pyrogov; Department of Nervous Diseases
🇺🇦Vinnytsya, Ukraine
Royal Hallamshire Hospital; Neurology
🇬🇧Sheffield, United Kingdom
East Bay Physicians Med Group;Sutter East Bay Med Foundation
🇺🇸Berkeley, California, United States
Bradenton Research Center
🇺🇸Bradenton, Florida, United States
Shepherd Center; Multiple Sclerosis Center
🇺🇸Atlanta, Georgia, United States
University of Chicago; Neurology
🇺🇸Chicago, Illinois, United States
John Hopkins University
🇺🇸Baltimore, Maryland, United States
Michigan Institute for Neurological Disorders
🇺🇸Farmington Hills, Michigan, United States
Suny At Stony Brook; Department Of Neurology
🇺🇸Stony Brook, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
St. Michael'S Hospital
🇨🇦Toronto, Ontario, Canada
Integra Clinical Research, Llc
🇺🇸San Antonio, Texas, United States
Unidad de Investigacion CIMA SC
🇲🇽Chihuahua, Mexico
Baylor College of Medicine
🇺🇸Houston, Texas, United States
Nemocnica s Poliklinikou Spisska Nova Ves, a.s.
🇸🇰Spisska Nova Ves, Slovakia
Uni of British Columbia Hospital; Ms Clinical Research Group
🇨🇦Vancouver, British Columbia, Canada
Instituto Biomedico De Investigacion A.C.
🇲🇽Aguascalientes, Mexico
Clinical Center of Serbia; Institute of Neurology
🇷🇸Belgrade, Serbia
Clinical Center Nis; Clinic for Mental Health
🇷🇸NIS, Serbia
Aarhus Universitetshospital; Neurologisk Afd. F, Skleroseklinikken
🇩🇰Aarhus N, Denmark
St. Joseph-Krankenhaus
🇩🇪Berlin, Germany
Barrow Neurological Institute
🇺🇸Phoenix, Arizona, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Dartmouth-Hitchcock Medical Center; Dept of Neurology
🇺🇸Lebanon, New Hampshire, United States
The Neurological Institute PA
🇺🇸Charlotte, North Carolina, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
University of Virginia - Fontain Research Park
🇺🇸Charlottesville, Virginia, United States
UZ Antwerpen
🇧🇪Edegem, Belgium
Military Medical Academy; Neurology
🇧🇬Sofia, Bulgaria
UMHAT Tzaritza Yoanna Sofia; CLINIC OF NEUROLOGY
🇧🇬Sofia, Bulgaria
Fakultni Nemocnice Ostrava; Klinika hematoonkologie FNO a LF OU
🇨🇿Ostrava, Czechia
McGill University; Montreal Neurological Institute; Neurological and Psychiatric
🇨🇦Montreal, Quebec, Canada
Krajska Nemocnice Pardubice Neurologicka Klinika
🇨🇿Pardubice, Czechia
Fakultni nemocnice Motol; Neurologicka klinika
🇨🇿Praha, Czechia
Hopital Pellegrin-CHU de Bordeaux; Service de Neurologie
🇫🇷Bordeaux, France
CHU De Caen; Service De Neurologie Dejerine
🇫🇷Caen, France
CHU De Nimes, Hopital Caremeau; Service De Neurologie Du Prof. Pierre Labauge
🇫🇷Nimes, France
Hospital CIMA, Sta. Engracia
🇲🇽Monterrey, Nuevo LEON, Mexico
Universitatsklinikum Marburg; Zentrum für Nervenheilkunde, Klinik für Psychiatrie+Psychotherapie
🇩🇪Marburg, Germany
Hospital Cima Chihauhau
🇲🇽Chihuahua, Mexico
Ospedale S.Andrea-Universita di Roma; Centro Sclerosi Multipla
🇮🇹Roma, Lazio, Italy
Spitalul Clinic Colentina; Clinica de Neurologie
🇷🇴Bucuresti, Romania
Spitalul Clinic Judetean de Urgenta Targu Mures; Clinica Neurologie
🇷🇴Targu Mures, Romania
Municipal City Hospital #33; Neurology
🇷🇺Nizhny Novgorod, Niznij Novgorod, Russian Federation
Central Clinical Hospital #2 N.A. Semashko OAO RJHD
🇷🇺Moskva, Moskovskaja Oblast, Russian Federation
Clinic of Neurology
🇷🇸Nova Sad, Serbia
Fakultna Nemocnica, Pracovisko Stare Mesto; Neurology
🇸🇰Bratislava, Slovakia
Fakultna Nemocnica Paterua, Pracovisko Trieda Snp1 Kosice; Neurologicka Klinika
🇸🇰Kosice, Slovakia
Fakultna Nemocnica F. D. Roosevelta; Ii. Neurologicka Klinika Szu
🇸🇰Banska Bystrica, Slovakia
Hospital Universitari Vall d'Hebron; Servicio de Neumo-Inmunologia
🇪🇸Barcelona, Spain
Hospital Regional Universitario Carlos Haya; Servicio de Neurologia
🇪🇸Malaga, Spain
Universitätsspital Basel; Neurologie
🇨ðŸ‡Basel, Switzerland
Uni Hospital Queens Medical Centre; Neurology
🇬🇧Nottingham, United Kingdom
Fletcher Allen Health Care/University of Vermont
🇺🇸Burlington, Vermont, United States
Asklepios Klinik Nord-Heidberg; Neurologie
🇩🇪Hamburg, Germany
Regional Multiple Sclerosis Centre b/o CC ECM Neftyanik; Neurology
🇷🇺Tyumen, Tjumen, Russian Federation
First MHAT; Clinic of Neurology
🇧🇬Sofia, Bulgaria
Kansas University Medical Center
🇺🇸Kansas City, Kansas, United States
Island Neurological Associates, P.C.
🇺🇸Plainview, New York, United States
Advanced Neurology of Colorado, LLC
🇺🇸Fort Collins, Colorado, United States
Clinical Research of Winston Salem
🇺🇸Winston-Salem, North Carolina, United States
Legacy Health System; Clinical Research & Tech Ctr
🇺🇸Tualatin, Oregon, United States
Ohio State University Med Ctr; MS Center
🇺🇸Columbus, Ohio, United States
Hopital Gabriel Montpied CHU de Clermont-Ferrand; Service de Neurologie B
🇫🇷Clermont-Ferrand, France
Shat of Cardiovascular Diseases; Clinic of Neurology
🇧🇬Sofia, Bulgaria
ACIBADEM CITY CLINIC TOKUDA HOSPITAL EAD; Clinic of Neurology and Sleep Medicine
🇧🇬Sofia, Bulgaria
Nemocnice Teplice; Neurologicke Oddeleni - Ms Centrum
🇨🇿Teplice, Czechia
Jüdisches Krankenhaus Berlin; Abteilung fur Neurologie
🇩🇪Berlin, Germany
SHI Sverdlovsk Regional Clinical Hospital #1;Neurology
🇷🇺Yekaterinburg, Sverdlovsk, Russian Federation
LLC Research Medical Complex Vashe Zdorovie
🇷🇺Kazan, Tatarstan, Russian Federation
Hospital Clinic i Provincial; Servicio de Neurologia
🇪🇸Barcelona, Spain
Hospital Universitario Virgen Macarena; Servicio de Neurologia
🇪🇸Sevilla, Spain
Hospital Ramon y Cajal; Servicio de Neurologia
🇪🇸Madrid, Spain
MRC for Oncology and Neurology; Neurology
🇷🇺Novosibirsk, Russian Federation
Hospital Universitario La Fe; Unidad de Esclerosis Multiple
🇪🇸Valencia, Spain
Walton Centre NHS Foundation Trust, Neuroscience Research Centre; CLINICAL TRIALS UNIT
🇬🇧Liverpool, United Kingdom
City Clin.Hosp #4; Dept. of Neurology
🇺🇦Kyiv, Ukraine
Ams of Ukraine; Inst. of Neurology, Psychiatry & Narcology
🇺🇦Kharkov, Ukraine
Ukr.State Inst. of Med and Social Probl. Disab; Dept of Neur and Border states
🇺🇦Propetrovsk, Ukraine