Multiple Sclerosis Clinical Trial

Study to Explore the Mechanism of Action of Ocrelizumab and B-Cell Biology in Participants With Relapsing Multiple Sclerosis (RMS) or Primary Progressive Multiple Sclerosis (PPMS)

Summary

This is an open-label, multicenter, biomarker study designed to be hypothesis-generating in order to better understand the mechanism of action of ocrelizumab and B-cell biology in RMS or PPMS. The study will be conducted in two cohorts i.e. RMS cohort (4 arm group) and PPMS cohort (one arm group). RMS cohort: Ocrelizumab will be administered as two intravenous (IV) infusions of 300 milligrams (mg) on Days 1 and 15. Subsequent doses will be given as single 600-mg infusions at Weeks 24 and 48. Participants will be randomized in 1:1:1 ratio to receive lumbar puncture (LP) post-treatment at Week 12, 24, or 52 following the first dose of ocrelizumab in three arm groups. A fourth RMS arm with delayed treatment start (Arm 4 [control group]) will not be a part of the randomization and will be recruited separately, wherein treatment with ocrelizumab will be delayed for 12 weeks from pre-treatment baseline. PPMS cohort: Ocrelizumab 600 mg will be administered as two 300-mg IV infusions separated by 14 days at a scheduled interval of every 24 weeks. Participants will receive a LP at the start of the study before dosing with ocrelizumab and second LP at Week 52 following the first dose of ocrelizumab. A long-term extension will be conducted for participants that complete the study and continue to receive ocrelizumab. Treatment with ocrelizumab in the entire study will continue for approximately 4.5 years after the first infusion.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

General Inclusion Criteria:

For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of <1 percent (%) per year during the treatment period and for at least 24 weeks after the last dose of study treatment or until their B-cells have repleted, whichever is longer

Inclusion Criteria Specific to RMS Participants:

Diagnosis of RMS in accordance with the 2010 revised McDonald criteria
Expanded Disability Status Scale (EDSS) score of 0 to 5.5 points, inclusive, at Screening
Disease duration from the onset of multiple sclerosis symptoms less than (<) 15 years in participants with an EDSS score greater than (>) 5.0 at Screening
Either treatment-naive or receiving treatment with disease-modifying therapies, including prior use of interferon (IFN)-beta-1a (Avonex®, Rebif®), IFN-beta-1b (Betaseron®/Betaferon), or glatiramer acetate (Copaxone®).
At least one clinically documented relapse in the past year and/or at least one T1-weighted Gadolinium (Gd)-enhancing lesion in the past year and/or at least one new T2 lesion in the past year at the time of enrollment

Inclusion Criteria Specific to RMS Cohort Arm 4 Participants:

Must meet inclusion criteria for the RMS cohort
Separate signed Informed Consent Form for the RMS Delayed Time to Start Control Arm (Arm 4)
Must be willing to remain on the same dose and regimen of current standard of care, or no treatment if treatment-naïve, for 12 weeks after study enrollment The treating and/or study physician must agree that the participant is eligible to remain on the same dose and regimen of their current standard of care at Screening, or to receive no treatment if the participant is treatment-naïve, for 12 weeks after study enrollment

Inclusion Criteria Specific to PPMS Participants:

Diagnosis of PPMS in accordance with the 2010 revised McDonald criteria
EDSS score of 3.0 - 6.5 points, inclusive, at Screening
Disease duration from the onset of multiple sclerosis symptoms <10 years in participants with an EDSS at Screening less than or equal to ( Documented history of either elevated immunoglobulin G (IgG) Index or one or more IgG oligoclonal bands (OCBs) detected by isoelectric focusing

Exclusion Criteria:

Diagnosis of secondary progressive multiple sclerosis without relapses for at least 1 year
History or known presence of recurrent or chronic infection (e.g., human immunodeficiency virus [HIV], syphilis, tuberculosis)
History of recurrent aspiration pneumonia requiring antibiotic therapy
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 with documented clean margins on pathology)
History of or currently active primary or secondary immunodeficiency
History of coagulation disorders
History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
History of alcohol or other drug abuse within 24 weeks prior to enrollment
Known presence or history of other neurologic disorders Significant, uncontrolled disease, such as cardiovascular (including cardiac arrhythmia), pulmonary (including chronic obstructive pulmonary disease), renal, hepatic, endocrine, gastrointestinal, or any other significant disease
Congestive heart failure (according to New York Heart Association III or IV functional severity)
Known active bacterial, viral, fungal, mycobacterial infection, or any major episode of infection requiring hospitalization or treatment with IV antibiotics
Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
Contraindications or intolerance to oral or IV corticosteroids, including IV methylprednisolone, according to the country label
Contraindication for LP
Previous treatment with B cell-targeted therapies (such as rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab)
Previous treatment with natalizumab/Tysabri®, alemtuzumab, anti-CD4 agents, cladribine, teriflunomide, cyclophosphamide, mitoxantrone, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, total body irradiation, or bone marrow transplantation
Treatment with fingolimod/Gilenya®, dimethyl fumarate/Tecfidera®, or similar treatment within 6 months prior to enrollment
Receipt of a live vaccine within 6 weeks prior to enrollment
Systemic corticosteroid therapy within 4 weeks prior to Baseline
Previous or concurrent treatment with any investigational agent or treatment with any experimental procedure for multiple sclerosis (such as treatment for chronic cerebrospinal venous insufficiency)
Certain laboratory abnormalities or findings at Screening
Inability to complete an MRI
Lack of peripheral venous access
Pregnant or lactating, or intending to become pregnant during the study

Exclusion Criteria Specific to RMS Participants:

Diagnosis of PPMS or secondary progressive multiple sclerosis without relapses

Study is for people with:

Multiple Sclerosis

Phase:

Phase 3

Estimated Enrollment:

132

Study ID:

NCT02688985

Recruitment Status:

Completed

Sponsor:

Genentech, Inc.

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There are 16 Locations for this study

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Stanford University
Palo Alto California, 94303, United States
University of California at San Francisco
San Francisco California, 94115, United States
University Of Colorado
Aurora Colorado, 80045, United States
Yale University School of Medicine ; Pulmonary & Critical Care
New Haven Connecticut, 06510, United States
University of Massachusetts Medical School
Worcester Massachusetts, 01655, United States
Washington University; Wash Uni. Sch. Of Med
Saint Louis Missouri, 63110, United States
Empire Neurology, PC
Latham New York, 12210, United States
Weill Cornell MC-NY Presbyter; Dept. of Neurology/Neuroscience, Judith Jaffe Multiple Sclerosis Ctr
New York New York, 63110, United States
University of North Carolina at Chapel Hill
Chapel Hill North Carolina, 27599, United States
Ohio State University
Columbus Ohio, 43210, United States
Oklahoma Medical Research Foundation; MS Center of Excellence
Oklahoma City Oklahoma, 73104, United States
University of Texas Southwestern Medical Center
Dallas Texas, 75390, United States
University of British Columbia Hospital Site; Djavad Mowafaghian Centre for Brain Health
Vancouver British Columbia, V6T 1, Canada
McGill University; Montreal Neurological Institute; Neurological and Psychiatric
Montreal Quebec, H3A 2, Canada
Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden
Dresden , 01307, Germany
Universitätsmedizin Göttingen Georg-August-Universität
Göttingen , 37075, Germany
Karolinska Universitetssjukhuset, Solna
Stockholm , 113 4, Sweden

How clear is this clinincal trial information?

Study is for people with:

Multiple Sclerosis

Phase:

Phase 3

Estimated Enrollment:

132

Study ID:

NCT02688985

Recruitment Status:

Completed

Sponsor:


Genentech, Inc.

How clear is this clinincal trial information?

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