A Study of the Efficacy and Safety of Ocrelizumab in Patients With Relapsing-Remitting Multiple Sclerosis

Phase II, Multicenter, Randomized, Parallel-Group, Partially Blinded, Placebo and Avonex Controlled Dose Finding Study to Evaluate the Efficacy As Measured by Brain MRI Lesions, and Safety of 2 Dose Regimens of Ocrelizumab in Patients With RRMS

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).

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis, Relapsing-Remitting
• Intervention / Treatment: Drug: Placebo; Drug: Ocrelizumab; Drug: Avonex

• Study Type: Interventional
• Enrollment (Actual): 220
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • UZ Antwerpen
• Bulgaria
  • Sofia, Bulgaria, 1407
    • ACIBADEM CITY CLINIC TOKUDA HOSPITAL EAD; Clinic of Neurology and Sleep Medicine
  • Sofia, Bulgaria, 1000
    • First MHAT; Clinic of Neurology
  • Sofia, Bulgaria, 1606
    • Military Medical Academy; Neurology
  • Sofia, Bulgaria, 1309
    • Shat of Cardiovascular Diseases; Clinic of Neurology
  • Sofia, Bulgaria, 1527
    • UMHAT Tzaritza Yoanna Sofia; CLINIC OF NEUROLOGY
  • Sofia, Bulgaria, 1606
    • CCB Medical institute, Ministry of Interior Sofia; CLINIC OF NEUROLOGY
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V6T 2B5
      • Uni of British Columbia Hospital; Ms Clinical Research Group
  • Ontario
    • Toronto, Ontario, Canada, M5B 1W8
      • St. Michael's Hospital
  • Quebec
    • Montreal, Quebec, Canada, H3A 2B4
      • McGill University; Montreal Neurological Institute; Neurological and Psychiatric
• Czechia
  • Ostrava, Czechia, 708 52
    • Fakultni Nemocnice Ostrava; Klinika hematoonkologie FNO a LF OU
  • Pardubice, Czechia, 532 03
    • Krajska Nemocnice Pardubice Neurologicka Klinika
  • Praha, Czechia, 150 06
    • Fakultni nemocnice Motol; Neurologicka klinika
  • Teplice, Czechia, 415 29
    • Nemocnice Teplice; Neurologicke Oddeleni - Ms Centrum
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus Universitetshospital; Neurologisk Afd. F, Skleroseklinikken
• France
  • Bordeaux, France, 33076
    • Hopital Pellegrin-CHU de Bordeaux; Service de Neurologie
  • Caen, France, 14033
    • CHU De Caen; Service De Neurologie Dejerine
  • Clermont-Ferrand, France, 63003
    • Hopital Gabriel Montpied CHU de Clermont-Ferrand; Service de Neurologie B
  • Nimes, France, 30029
    • CHU De Nimes, Hopital Caremeau; Service De Neurologie Du Prof. Pierre Labauge
• Germany
  • Berlin, Germany, 13347
    • Jüdisches Krankenhaus Berlin; Abteilung fur Neurologie
  • Berlin, Germany, 13088
    • St. Joseph-Krankenhaus
  • Hamburg, Germany, 22417
    • Asklepios Klinik Nord-Heidberg; Neurologie
  • Marburg, Germany, 35039
    • Universitatsklinikum Marburg; Zentrum für Nervenheilkunde, Klinik für Psychiatrie+Psychotherapie
• Italy
  • Lazio
    • Roma, Lazio, Italy, 00189
      • Ospedale S.Andrea-Universita di Roma; Centro Sclerosi Multipla
• Mexico
  • Aguascalientes, Mexico, 20127
    • Instituto Biomedico De Investigacion A.C.
  • Chihuahua, Mexico, 31200
    • Unidad de Investigacion CIMA SC
  • Chihuahua, Mexico, 31328
    • Hospital Cima Chihauhau
  • Nuevo LEON
    • Monterrey, Nuevo LEON, Mexico, 64060
      • Hospital CIMA, Sta. Engracia
• Romania
  • Bucuresti, Romania, 020125
    • Spitalul Clinic Colentina; Clinica de Neurologie
  • Targu Mures, Romania, 540136
    • Spitalul Clinic Judetean de Urgenta Targu Mures; Clinica Neurologie
• Russian Federation
  • Novosibirsk, Russian Federation, 630090
    • MRC for Oncology and Neurology; Neurology
  • Moskovskaja Oblast
    • Moskva, Moskovskaja Oblast, Russian Federation, 107150
      • Central Clinical Hospital #2 N.A. Semashko OAO RJHD
  • Niznij Novgorod
    • Nizhny Novgorod, Niznij Novgorod, Russian Federation, 603076
      • Municipal City Hospital #33; Neurology
  • Sverdlovsk
    • Yekaterinburg, Sverdlovsk, Russian Federation, 620102
      • SHI Sverdlovsk Regional Clinical Hospital #1;Neurology
  • Tatarstan
    • Kazan, Tatarstan, Russian Federation, 4420029
      • LLC Research Medical Complex Vashe Zdorovie
  • Tjumen
    • Tyumen, Tjumen, Russian Federation, 625048
      • Regional Multiple Sclerosis Centre b/o CC ECM Neftyanik; Neurology
• Serbia
  • Belgrade, Serbia, 11000
    • Clinical Center of Serbia; Institute of Neurology
  • NIS, Serbia, 18000
    • Clinical Center Nis; Clinic for Mental Health
  • Nova Sad, Serbia, 21000
    • Clinic of Neurology
• Slovakia
  • Banska Bystrica, Slovakia, 975 17
    • Fakultna Nemocnica F. D. Roosevelta; Ii. Neurologicka Klinika Szu
  • Bratislava, Slovakia, 813 69
    • Fakultna Nemocnica, Pracovisko Stare Mesto; Neurology
  • Kosice, Slovakia, 041 66
    • Fakultna Nemocnica Paterua, Pracovisko Trieda Snp1 Kosice; Neurologicka Klinika
  • Nitra, Slovakia, 949 01
    • Fakultna Nemocnica Nitra; Neurologicka Klinika
  • Spisska Nova Ves, Slovakia, 05201
    • Nemocnica s poliklinikou Spisska Nova Ves, a.s.
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron; Servicio de Neumo-Inmunologia
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial; Servicio de Neurologia
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal; Servicio de Neurologia
  • Malaga, Spain, 29010
    • Hospital Regional Universitario Carlos Haya; Servicio de Neurologia
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena; Servicio de Neurologia
  • Valencia, Spain, 46026
    • Hospital Universitario La Fe; Unidad de Esclerosis Multiple
• Switzerland
  • Basel, Switzerland, 4031
    • Universitätsspital Basel; Neurologie
• Ukraine
  • Kharkov, Ukraine, 61068
    • Ams of Ukraine; Inst. of Neurology, Psychiatry & Narcology
  • Kyiv, Ukraine, 03110
    • City Clin.Hosp #4; Dept. of Neurology
  • Propetrovsk, Ukraine, 49027
    • Ukr.State Inst. of Med and Social Probl. Disab; Dept of Neur and Border states
  • Vinnytsya, Ukraine, 21005
    • Vin.Reg.Psych.Hosp.N.A Yuschenko O.I., Vnmu N.A. Pyrogov; Department of Nervous Diseases
• United Kingdom
  • Liverpool, United Kingdom, L9 7LJ
    • Walton Centre NHS Foundation Trust, Neuroscience Research Centre; CLINICAL TRIALS UNIT
  • Nottingham, United Kingdom, NG7 2UH
    • Uni Hospital Queens Medical Centre; Neurology
  • Sheffield, United Kingdom, S10 2JF
    • Royal Hallamshire Hospital; Neurology
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurological Institute
    • Phoenix, Arizona, United States, 85006
      • Phoenix Neurological Associates Ltd
  • California
    • Berkeley, California, United States, 94705
      • East Bay Physicians Med Group;Sutter East Bay Med Foundation
    • San Francisco, California, United States, 94117
      • University of California San Francisco
  • Colorado
    • Fort Collins, Colorado, United States, 80528
      • Advanced Neurology of Colorado, LLC
  • Florida
    • Bradenton, Florida, United States, 34205
      • Bradenton Research Center
    • Vero Beach, Florida, United States, 32960
      • MS Center of Vero Beach
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Shepherd Center; Multiple Sclerosis Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago; Neurology
  • Kansas
    • Kansas City, Kansas, United States, 66103
      • Kansas University Medical Center
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • John Hopkins University
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Michigan Institute for Neurological Disorders
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center; Dept of Neurology
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center; The Neurological Institute of New York
    • Plainview, New York, United States, 11803
      • Island Neurological Associates, P.C.
    • Stony Brook, New York, United States, 11794
      • Suny At Stony Brook; Department Of Neurology
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • The Neurological Institute PA
    • Winston-Salem, North Carolina, United States, 27103
      • Clinical Research of Winston Salem
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • Cleveland Clinic
    • Columbus, Ohio, United States, 43221
      • Ohio State University Med Ctr; MS Center
  • Oregon
    • Tualatin, Oregon, United States, 97062
      • Legacy Health System; Clinical Research & Tech Ctr
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • San Antonio, Texas, United States, 78229
      • Integra Clinical Research, Llc
  • Vermont
    • Burlington, Vermont, United States, 5405
      • Fletcher Allen Health Care/University of Vermont
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia - Fontain Research Park

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 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.	Drug: Placebo; Placebo matching to ocrelizumab administered as IV infision in Cycle 1 Day 1.
Experimental: Ocrelizumab 600 mg; 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.	Drug: Ocrelizumab; Ocrelizumab 300 mg was administered in cycle 1 followed by an infusion of ocrelizumab 600 mg on Day 1. A single infusion of ocrelizumab 600 mg was administered on Day 1 of cycles 3 and 4.; Other Names: RO4964913
Experimental: Ocrelizumab 1000 mg; 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.	Drug: Ocrelizumab; Ocrelizumab 300 mg was administered in cycle 1 followed by an infusion of ocrelizumab 600 mg on Day 1. A single infusion of ocrelizumab 600 mg was administered on Day 1 of cycles 3 and 4.; Other Names: RO4964913
Active Comparator: 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.	Drug: Avonex; Avonex was administered weekly intramuscular injections of 30 mcg in cycle 1 Day 1.; Other Names: Interferon-beta-alpha1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Number of Gadolinium-Enhancing T1 Lesions Observed on MRI Scans of the Brain	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.	Week 12 to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Protocol Defined Relapse Rate at Week 24	Adjusted annualized relapse rate for geographical region.	Week 24
Percentage of Participants Who Remained Relapse Free at Week 24	Percentage of participants who remained relapse free at week 24 were reported.	Week 24
Change From Baseline in Total Volume of T2 Lesions on MRI Scans of the Brain at Week 24	Change from baseline in total volume of T2 lesions on MRI scans of the Brain at week 24 was reported.	Baseline, Week 24
Total Number of New Gadolinium-Enhancing T1 Lesions Observed by MRI Scans of the Brain	Total number of new gadolinium-enhancing T1 lesions observed by MRI scans of the brain were reported.	Weeks 4 to Week 24
Total Number of Gadolinium-Enhancing T1 Lesions at Weeks	Total number of gadolinium-enhancing T1 lesions at weeks were reported.	Weeks 4 to Week 24

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Collaborators: Roche Pharma AG
• Investigators: Study Director: Clinical Trials, Genentech, Inc.

Publications and helpful links

General Publications

• Kappos L, Li D, Calabresi PA, O'Connor P, Bar-Or A, Barkhof F, Yin M, Leppert D, Glanzman R, Tinbergen J, Hauser SL. Ocrelizumab in relapsing-remitting multiple sclerosis: a phase 2, randomised, placebo-controlled, multicentre trial. Lancet. 2011 Nov 19;378(9805):1779-87. doi: 10.1016/S0140-6736(11)61649-8. Epub 2011 Oct 31.

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2008
• Primary Completion (Actual): March 9, 2012
• Study Completion (Actual): November 8, 2023

Study Registration Dates

• First Submitted: May 9, 2008
• First Submitted That Met QC Criteria: May 9, 2008
• First Posted (Estimated): May 13, 2008

Study Record Updates

• Last Update Posted (Estimated): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 17, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Anti-Infective Agents; Antiviral Agents; Antineoplastic Agents; Immunologic Factors; Interferons; Ocrelizumab; Interferon-beta
• Other Study ID Numbers: ACT4422g; 2007-006338-32 (EudraCT Number); WA21493 (Other Identifier: Hoffmann-La Roche)