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

Multiple Sclerosis, Relapsing-Remitting Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00676715
• Other study ID #: ACT4422g
• Secondary ID: 2007-006338-32WA
• Status: Completed
• Phase: Phase 2
• Start date: July 17, 2008
• Est. completion date: November 8, 2023

Study information

• Verified date: February 2024
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 220
• Est. completion date: November 8, 2023
• Est. primary completion date: March 9, 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

Drug:
• Placebo
Placebo matching to ocrelizumab administered as IV infision in Cycle 1 Day 1.
• 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.
• Avonex
Avonex was administered weekly intramuscular injections of 30 mcg in cycle 1 Day 1.

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Genentech, Inc.	Roche Pharma AG

Countries where clinical trial is conducted

United States,  Belgium,  Bulgaria,  Canada,  Czechia,  Denmark,  France,  Germany,  Italy,  Mexico,  Romania,  Russian Federation,  Serbia,  Slovakia,  Spain,  Switzerland,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Annualized Protocol Defined Relapse Rate at Week 24	Adjusted annualized relapse rate for geographical region.	Week 24
Secondary	Percentage of Participants Who Remained Relapse Free at Week 24	Percentage of participants who remained relapse free at week 24 were reported.	Week 24
Secondary	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
Secondary	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
Secondary	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