Clinical trial NCT00676715: A Study of the Efficacy and Safety of Ocrelizumab in Patients With Relapsing-Remitting Multiple Sclerosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Sclerosis, Relapsing-Remitting
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Roche Pharma AG
First posted: 2008-05-13
Enrollment: 220
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 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).


Eligibility criteria: 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

Primary outcomes:
measure: Total Number of Gadolinium-Enhancing T1 Lesions Observed on Magnetic Resonance Imaging (MRI) Scans of the Brain
timeFrame: Week 12 to Week 24
Secondary outcomes:
measure: Annualized Protocol Defined Relapse Rate at Week 24
timeFrame: Week 24
measure: Percentage of Participants Who Remained Relapse Free at Week 24
timeFrame: Week 24
measure: Change From Baseline in Total Volume of T2 Lesions on MRI Scans of the Brain at Week 24
timeFrame: Baseline, Week 24
measure: Total Number of New Gadolinium-Enhancing T1 Lesions Observed by MRI Scans of the Brain
timeFrame: Weeks 4 to Week 24
measure: Total Number of Gadolinium-Enhancing T1 Lesions
timeFrame: Weeks 4 to Week 24
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Neurological Associates Ltd
state: Arizona
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Berkeley
country: United States
facility: East Bay Physicians Med Group;Sutter East Bay Med Foundation
state: California
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Fort Collins
country: United States
facility: Advanced Neurology of Colorado, LLC
state: Colorado
city: Bradenton
country: United States
facility: Bradenton Research Center
state: Florida
city: Vero Beach
country: United States
facility: MS Center of Vero Beach
state: Florida
city: Atlanta
country: United States
facility: Shepherd Center; Multiple Sclerosis Center
state: Georgia
city: Chicago
country: United States
facility: University of Chicago; Neurology
state: Illinois
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Baltimore
country: United States
facility: John Hopkins University
state: Maryland
city: Farmington Hills
country: United States
facility: Michigan Institute for Neurological Disorders
state: Michigan
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center; Dept of Neurology
state: New Hampshire
city: New York
country: United States
facility: Columbia University Medical Center; The Neurological Institute of New York
state: New York
city: Plainview
country: United States
facility: Island Neurological Associates, P.C.
state: New York
city: Stony Brook
country: United States
facility: Suny At Stony Brook; Department Of Neurology
state: New York
city: Charlotte
country: United States
facility: The Neurological Institute PA
state: North Carolina
city: Winston-Salem
country: United States
facility: Clinical Research of Winston Salem
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Med Ctr; MS Center
state: Ohio
city: Tualatin
country: United States
facility: Legacy Health System; Clinical Research & Tech Ctr
state: Oregon
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: Integra Clinical Research, Llc
state: Texas
city: Burlington
country: United States
facility: Fletcher Allen Health Care/University of Vermont
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia - Fontain Research Park
state: Virginia
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Sofia
country: Bulgaria
facility: First MHAT; Clinic of Neurology
city: Sofia
country: Bulgaria
facility: Shat of Cardiovascular Diseases; Clinic of Neurology
city: Sofia
country: Bulgaria
facility: ACIBADEM CITY CLINIC TOKUDA HOSPITAL EAD; Clinic of Neurology and Sleep Medicine
city: Sofia
country: Bulgaria
facility: UMHAT Tzaritza Yoanna Sofia; CLINIC OF NEUROLOGY
city: Sofia
country: Bulgaria
facility: CCB Medical institute, Ministry of Interior Sofia; CLINIC OF NEUROLOGY
city: Sofia
country: Bulgaria
facility: Military Medical Academy; Neurology
city: Vancouver
country: Canada
facility: Uni of British Columbia Hospital; Ms Clinical Research Group
state: British Columbia
city: Toronto
country: Canada
facility: St. Michael'S Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University; Montreal Neurological Institute; Neurological and Psychiatric
state: Quebec
city: Ostrava
country: Czechia
facility: Fakultni Nemocnice Ostrava; Klinika hematoonkologie FNO a LF OU
city: Pardubice
country: Czechia
facility: Krajska Nemocnice Pardubice Neurologicka Klinika
city: Praha
country: Czechia
facility: Fakultni nemocnice Motol; Neurologicka klinika
city: Teplice
country: Czechia
facility: Nemocnice Teplice; Neurologicke Oddeleni - Ms Centrum
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital; Neurologisk Afd. F, Skleroseklinikken
city: Bordeaux
country: France
facility: Hopital Pellegrin-CHU de Bordeaux; Service de Neurologie
city: Caen
country: France
facility: CHU De Caen; Service De Neurologie Dejerine
city: Clermont-Ferrand
country: France
facility: Hopital Gabriel Montpied CHU de Clermont-Ferrand; Service de Neurologie B
city: Nimes
country: France
facility: CHU De Nimes, Hopital Caremeau; Service De Neurologie Du Prof. Pierre Labauge
city: Berlin
country: Germany
facility: St. Joseph-Krankenhaus
city: Berlin
country: Germany
facility: Jüdisches Krankenhaus Berlin; Abteilung fur Neurologie
city: Hamburg
country: Germany
facility: Asklepios Klinik Nord-Heidberg; Neurologie
city: Marburg
country: Germany
facility: Universitatsklinikum Marburg; Zentrum für Nervenheilkunde, Klinik für Psychiatrie+Psychotherapie
city: Roma
country: Italy
facility: Ospedale S.Andrea-Universita di Roma; Centro Sclerosi Multipla
state: Lazio
city: Monterrey
country: Mexico
facility: Hospital CIMA, Sta. Engracia
state: Nuevo LEON
city: Aguascalientes
country: Mexico
facility: Instituto Biomedico De Investigacion A.C.
city: Chihuahua
country: Mexico
facility: Unidad de Investigacion CIMA SC
city: Chihuahua
country: Mexico
facility: Hospital Cima Chihauhau
city: Bucuresti
country: Romania
facility: Spitalul Clinic Colentina; Clinica de Neurologie
city: Targu Mures
country: Romania
facility: Spitalul Clinic Judetean de Urgenta Targu Mures; Clinica Neurologie
city: Moskva
country: Russian Federation
facility: Central Clinical Hospital #2 N.A. Semashko OAO RJHD
state: Moskovskaja Oblast
city: Nizhny Novgorod
country: Russian Federation
facility: Municipal City Hospital #33; Neurology
state: Niznij Novgorod
city: Yekaterinburg
country: Russian Federation
facility: SHI Sverdlovsk Regional Clinical Hospital #1;Neurology
state: Sverdlovsk
city: Kazan
country: Russian Federation
facility: LLC Research Medical Complex Vashe Zdorovie
state: Tatarstan
city: Tyumen
country: Russian Federation
facility: Regional Multiple Sclerosis Centre b/o CC ECM Neftyanik; Neurology
state: Tjumen
city: Novosibirsk
country: Russian Federation
facility: MRC for Oncology and Neurology; Neurology
city: Belgrade
country: Serbia
facility: Clinical Center of Serbia; Institute of Neurology
city: NIS
country: Serbia
facility: Clinical Center Nis; Clinic for Mental Health
city: Nova Sad
country: Serbia
facility: Clinic of Neurology
city: Banska Bystrica
country: Slovakia
facility: Fakultna Nemocnica F. D. Roosevelta; Ii. Neurologicka Klinika Szu
city: Bratislava
country: Slovakia
facility: Fakultna Nemocnica, Pracovisko Stare Mesto; Neurology
city: Kosice
country: Slovakia
facility: Fakultna Nemocnica Paterua, Pracovisko Trieda Snp1 Kosice; Neurologicka Klinika
city: Nitra
country: Slovakia
facility: Fakultna Nemocnica Nitra; Neurologicka Klinika
city: Spisska Nova Ves
country: Slovakia
facility: Nemocnica s Poliklinikou Spisska Nova Ves, a.s.
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron; Servicio de Neumo-Inmunologia
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial; Servicio de Neurologia
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal; Servicio de Neurologia
city: Malaga
country: Spain
facility: Hospital Regional Universitario Carlos Haya; Servicio de Neurologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena; Servicio de Neurologia
city: Valencia
country: Spain
facility: Hospital Universitario La Fe; Unidad de Esclerosis Multiple
city: Basel
country: Switzerland
facility: Universitätsspital Basel; Neurologie
city: Kharkov
country: Ukraine
facility: Ams of Ukraine; Inst. of Neurology, Psychiatry & Narcology
city: Kyiv
country: Ukraine
facility: City Clin.Hosp #4; Dept. of Neurology
city: Propetrovsk
country: Ukraine
facility: Ukr.State Inst. of Med and Social Probl. Disab; Dept of Neur and Border states
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: Nottingham
country: United Kingdom
facility: Uni Hospital Queens Medical Centre; Neurology
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital; Neurology
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.