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)
Relapsing Multiple Sclerorsis, Multiple Sclerosis, Primary Progressive
About this trial
This is an interventional treatment trial for Relapsing Multiple Sclerorsis
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 (</=) 5.0
- 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
Sites / Locations
- Stanford University
- University of California at San Francisco
- University Of Colorado
- Yale University School of Medicine ; Pulmonary & Critical Care
- University of Massachusetts Medical School
- Washington University; Wash Uni. Sch. Of Med
- Empire Neurology, PC
- Weill Cornell MC-NY Presbyter; Dept. of Neurology/Neuroscience, Judith Jaffe Multiple Sclerosis Ctr
- University of North Carolina at Chapel Hill
- Ohio State University
- Oklahoma Medical Research Foundation; MS Center of Excellence
- University of Texas Southwestern Medical Center
- University of British Columbia Hospital Site; Djavad Mowafaghian Centre for Brain Health
- McGill University; Montreal Neurological Institute; Neurological and Psychiatric
- Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden
- Universitätsmedizin Göttingen Georg-August-Universität
- Karolinska Universitetssjukhuset, Solna
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Experimental
Experimental
Experimental
Experimental
Experimental
RMS Cohort Arm 1: Ocrelizumab + LP
RMS Cohort Arm 2: Ocrelizumab + LP
RMS Cohort Arm 3: Ocrelizumab + LP
RMS Cohort Arm 4: Ocrelizumab + LP
PPMS Cohort: Ocrelizumab + LP
Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP before the start of dosing (Week 1, treatment baseline) with ocrelizumab and a second LP at Week 12. Participants will be asked to have an additional optional LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72.
Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP before the start of dosing (Week 1, treatment baseline) with ocrelizumab and a second LP at Week 24. Participants will be asked to have an additional optional LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72.
Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP before the start of dosing (Week 1, treatment baseline) with ocrelizumab and a second LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72.
Ocrelizumab treatment will be delayed for 12 weeks from pre-treatment baseline. Participants with RMS will receive ocrelizumab as two 300-mg IV infusion on Days 1 and 15 then as single infusion of 600 mg on Weeks 24 and 48. Participants will receive a LP at Week -12 (pre-treatment baseline) and a second LP before the start of dosing (Week 1, treatment baseline). Participants will be asked to have an additional optional LP at Week 52. Participants that complete the study and continue to receive ocrelizumab will receive single infusions every 24 weeks starting from Week 72.
For the PPMS cohort, ocrelizumab will be administered as two 300-mg IV infusions separated by 14 days at a scheduled interval of every 24 weeks during the treatment period and then as a single 600-mg dose every 24 weeks starting week 72 during the Long-Term Extension period.