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

NCT00676715 | Completed Phase 2 Results

• 3 other identifiers: ACT4422g2007-006338-32WA21493
• Study Type: interventional
• Target: 220
• Locations: 18 countries
• Sites: 84

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).

Conditions

Multiple Sclerosis, Relapsing-Remitting

Outcome Measures

Primary Outcomes (1)

• Total Number of Gadolinium-Enhancing T1 Lesions Observed on Magnetic Resonance Imaging (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 Outcomes (5)

• Annualized Protocol Defined Relapse Rate at Week 24

  Week 24

• Percentage of Participants Who Remained Relapse Free at Week 24

  Week 24

• Change From Baseline in Total Volume of T2 Lesions on MRI Scans of the Brain at Week 24

  Baseline, Week 24

• Total Number of New Gadolinium-Enhancing T1 Lesions Observed by MRI Scans of the Brain

  Weeks 4 to Week 24

• Total Number of Gadolinium-Enhancing T1 Lesions

  Weeks 4 to Week 24

Study Arms (4)

Placebo

PLACEBO COMPARATOR

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

Ocrelizumab 600 mg

EXPERIMENTAL

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 1000 mg

EXPERIMENTAL

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

Avonex

ACTIVE COMPARATOR

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

Interventions

Placebo DRUG

Placebo matching to ocrelizumab administered as IV infision in Cycle 1 Day 1.

Placebo

Ocrelizumab DRUG

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.

Also known as: RO4964913

Ocrelizumab 1000 mg; Ocrelizumab 600 mg

Avonex DRUG

Avonex was administered weekly intramuscular injections of 30 mcg in cycle 1 Day 1.

Also known as: Interferon-beta-alpha1

Avonex

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead
• Roche Pharma AG: collaborator

Study Sites (84)

Phoenix Neurological Associates Ltd

Phoenix, Arizona, 85006, United States

Location

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

East Bay Physicians Med Group;Sutter East Bay Med Foundation

Berkeley, California, 94705, United States

Location

University of California San Francisco

San Francisco, California, 94117, United States

Location

Advanced Neurology of Colorado, LLC

Fort Collins, Colorado, 80528, United States

Location

Bradenton Research Center

Bradenton, Florida, 34205, United States

Location

MS Center of Vero Beach

Vero Beach, Florida, 32960, United States

Location

Shepherd Center; Multiple Sclerosis Center

Atlanta, Georgia, 30309, United States

Location

University of Chicago; Neurology

Chicago, Illinois, 60637, United States

Location

Kansas University Medical Center

Kansas City, Kansas, 66103, United States

Location

John Hopkins University

Baltimore, Maryland, 21205, United States

Location

Michigan Institute for Neurological Disorders

Farmington Hills, Michigan, 48334, United States

Location

Dartmouth-Hitchcock Medical Center; Dept of Neurology

Lebanon, New Hampshire, 03756, United States

Location

Columbia University Medical Center; The Neurological Institute of New York

New York, New York, 10032, United States

Location

Island Neurological Associates, P.C.

Plainview, New York, 11803, United States

Location

Suny At Stony Brook; Department Of Neurology

Stony Brook, New York, 11794, United States

Location

The Neurological Institute PA

Charlotte, North Carolina, 28204, United States

Location

Clinical Research of Winston Salem

Winston-Salem, North Carolina, 27103, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44106, United States

Location

Ohio State University Med Ctr; MS Center

Columbus, Ohio, 43221, United States

Location

Legacy Health System; Clinical Research & Tech Ctr

Tualatin, Oregon, 97062, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Integra Clinical Research, Llc

San Antonio, Texas, 78229, United States

Location

Fletcher Allen Health Care/University of Vermont

Burlington, Vermont, 5405, United States

Location

University of Virginia - Fontain Research Park

Charlottesville, Virginia, 22903, United States

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

First MHAT; Clinic of Neurology

Sofia, 1000, Bulgaria

Location

Shat of Cardiovascular Diseases; Clinic of Neurology

Sofia, 1309, Bulgaria

Location

ACIBADEM CITY CLINIC TOKUDA HOSPITAL EAD; Clinic of Neurology and Sleep Medicine

Sofia, 1407, Bulgaria

Location

UMHAT Tzaritza Yoanna Sofia; CLINIC OF NEUROLOGY

Sofia, 1527, Bulgaria

Location

CCB Medical institute, Ministry of Interior Sofia; CLINIC OF NEUROLOGY

Sofia, 1606, Bulgaria

Location

Military Medical Academy; Neurology

Sofia, 1606, Bulgaria

Location

Uni of British Columbia Hospital; Ms Clinical Research Group

Vancouver, British Columbia, V6T 2B5, Canada

Location

St. Michael'S Hospital

Toronto, Ontario, M5B 1W8, Canada

Location

McGill University; Montreal Neurological Institute; Neurological and Psychiatric

Montreal, Quebec, H3A 2B4, Canada

Location

Fakultni Nemocnice Ostrava; Klinika hematoonkologie FNO a LF OU

Ostrava, 708 52, Czechia

Location

Krajska Nemocnice Pardubice Neurologicka Klinika

Pardubice, 532 03, Czechia

Location

Fakultni nemocnice Motol; Neurologicka klinika

Prague, 150 06, Czechia

Location

Nemocnice Teplice; Neurologicke Oddeleni - Ms Centrum

Teplice, 415 29, Czechia

Location

Aarhus Universitetshospital; Neurologisk Afd. F, Skleroseklinikken

Aarhus N, 8200, Denmark

Location

Hopital Pellegrin-CHU de Bordeaux; Service de Neurologie

Bordeaux, 33076, France

Location

CHU De Caen; Service De Neurologie Dejerine

Caen, 14033, France

Location

Hopital Gabriel Montpied CHU de Clermont-Ferrand; Service de Neurologie B

Clermont-Ferrand, 63003, France

Location

CHU De Nimes, Hopital Caremeau; Service De Neurologie Du Prof. Pierre Labauge

Nîmes, 30029, France

Location

St. Joseph-Krankenhaus

Berlin, 13088, Germany

Location

Jüdisches Krankenhaus Berlin; Abteilung fur Neurologie

Berlin, 13347, Germany

Location

Asklepios Klinik Nord-Heidberg; Neurologie

Hamburg, 22417, Germany

Location

Universitatsklinikum Marburg; Zentrum für Nervenheilkunde, Klinik für Psychiatrie+Psychotherapie

Marburg, 35039, Germany

Location

Ospedale S.Andrea-Universita di Roma; Centro Sclerosi Multipla

Rome, Lazio, 00189, Italy

Location

Hospital CIMA, Sta. Engracia

Monterrey, Nuevo León, 64060, Mexico

Location

Instituto Biomedico De Investigacion A.C.

Aguascalientes, 20127, Mexico

Location

Unidad de Investigacion CIMA SC

Chihuahua City, 31200, Mexico

Location

Hospital Cima Chihauhau

Chihuahua City, 31328, Mexico

Location

Spitalul Clinic Colentina; Clinica de Neurologie

Bucharest, 020125, Romania

Location

Spitalul Clinic Judetean de Urgenta Targu Mures; Clinica Neurologie

Târgu Mureş, 540136, Romania

Location

Central Clinical Hospital #2 N.A. Semashko OAO RJHD

Moskva, Moscow Oblast, 107150, Russia

Location

Municipal City Hospital #33; Neurology

Nizhny Novgorod, Niznij Novgorod, 603076, Russia

Location

SHI Sverdlovsk Regional Clinical Hospital #1;Neurology

Yekaterinburg, Sverdlovsk Oblast, 620102, Russia

Location

LLC Research Medical Complex Vashe Zdorovie

Kazan', Tatarstan Republic, 4420029, Russia

Location

Regional Multiple Sclerosis Centre b/o CC ECM Neftyanik; Neurology

Tyumen, Tyumen Oblast, 625048, Russia

Location

MRC for Oncology and Neurology; Neurology

Novosibirsk, 630090, Russia

Location

Clinical Center of Serbia; Institute of Neurology

Belgrade, 11000, Serbia

Location

Clinical Center Nis; Clinic for Mental Health

Niš, 18000, Serbia

Location

Clinic of Neurology

Nova Sad, 21000, Serbia

Location

Fakultna Nemocnica F. D. Roosevelta; Ii. Neurologicka Klinika Szu

Banská Bystrica, 975 17, Slovakia

Location

Fakultna Nemocnica, Pracovisko Stare Mesto; Neurology

Bratislava, 813 69, Slovakia

Location

Fakultna Nemocnica Paterua, Pracovisko Trieda Snp1 Kosice; Neurologicka Klinika

Košice, 041 66, Slovakia

Location

Fakultna Nemocnica Nitra; Neurologicka Klinika

Nitra, 949 01, Slovakia

Location

Nemocnica s Poliklinikou Spisska Nova Ves, a.s.

Spišská Nová Ves, 05201, Slovakia

Location

Hospital Universitari Vall d'Hebron; Servicio de Neumo-Inmunologia

Barcelona, 08035, Spain

Location

Hospital Clinic i Provincial; Servicio de Neurologia

Barcelona, 08036, Spain

Location

Hospital Ramon y Cajal; Servicio de Neurologia

Madrid, 28034, Spain

Location

Hospital Regional Universitario Carlos Haya; Servicio de Neurologia

Málaga, 29010, Spain

Location

Hospital Universitario Virgen Macarena; Servicio de Neurologia

Seville, 41009, Spain

Location

Hospital Universitario La Fe; Unidad de Esclerosis Multiple

Valencia, 46026, Spain

Location

Universitätsspital Basel; Neurologie

Basel, 4031, Switzerland

Location

Ams of Ukraine; Inst. of Neurology, Psychiatry & Narcology

Kharkiv, 61068, Ukraine

Location

City Clin.Hosp #4; Dept. of Neurology

Kyiv, 03110, Ukraine

Location

Ukr.State Inst. of Med and Social Probl. Disab; Dept of Neur and Border states

Propetrovsk, 49027, Ukraine

Location

Vin.Reg.Psych.Hosp.N.A Yuschenko O.I., Vnmu N.A. Pyrogov; Department of Nervous Diseases

Vinnytsia, 21005, Ukraine

Location

Walton Centre NHS Foundation Trust, Neuroscience Research Centre; CLINICAL TRIALS UNIT

Liverpool, L9 7LJ, United Kingdom

Location

Uni Hospital Queens Medical Centre; Neurology

Nottingham, NG7 2UH, United Kingdom

Location

Royal Hallamshire Hospital; Neurology

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 22047971 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

ocrelizumab; Interferon beta-1a

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interferon-beta; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2008
• First Posted: May 13, 2008
• Study Start: July 17, 2008
• Primary Completion: March 9, 2012
• Study Completion: November 8, 2023
• Last Updated: December 31, 2024
• Results First Posted: May 11, 2017

Record last verified: 2024-12

Locations

US (26); CZ (4); ME (4); CA (3); SE (3); SL (5); UA (4); GB (3); IT (1); RO (2); DK (1); FR (4); DE (4); ES (6); CH (1); BU (6); RU (6); BE (1)