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)

Last updated: May 7, 2024
Sponsor: Genentech, Inc.
Overall Status: Completed

Phase

3

Condition

Memory Loss

Scar Tissue

Multiple Sclerosis

Treatment

Lumbar Puncture

Methyloprednisolone

Ocrelizumab

Clinical Study ID

NCT02688985
ML29966
2015-004616-37
  • Ages 18-55
  • All Genders

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

General Inclusion Criteria:

  • For women of childbearing potential: agreement to remain abstinent (refrain fromheterosexual intercourse) or use contraceptive methods that result in a failure rateof <1 percent (%) per year during the treatment period and for at least 24 weeksafter 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, atScreening

  • Disease duration from the onset of multiple sclerosis symptoms less than (<) 15years 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 oneT1-weighted Gadolinium (Gd)-enhancing lesion in the past year and/or at least onenew 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 treatingand/or study physician must agree that the participant is eligible to remain on thesame dose and regimen of their current standard of care at Screening, or to receiveno treatment if the participant is treatment-naïve, for 12 weeks after studyenrollment

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 inparticipants with an EDSS at Screening less than or equal to (</=) 5.0

  • Documented history of either elevated immunoglobulin G (IgG) Index or one or moreIgG oligoclonal bands (OCBs) detected by isoelectric focusing

Exclusion

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., humanimmunodeficiency virus [HIV], syphilis, tuberculosis)

  • History of recurrent aspiration pneumonia requiring antibiotic therapy

  • History of cancer, including solid tumors and hematological malignancies (exceptbasal cell, in situ squamous cell carcinomas of the skin, and in situ carcinoma ofthe cervix of the uterus that have been excised and resolved with documented cleanmargins 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 murinemonoclonal antibodies

  • History of alcohol or other drug abuse within 24 weeks prior to enrollment

  • Known presence or history of other neurologic disorders Significant, uncontrolleddisease, such as cardiovascular (including cardiac arrhythmia), pulmonary (includingchronic obstructive pulmonary disease), renal, hepatic, endocrine, gastrointestinal,or any other significant disease

  • Congestive heart failure (according to New York Heart Association III or IVfunctional severity)

  • Known active bacterial, viral, fungal, mycobacterial infection, or any major episodeof infection requiring hospitalization or treatment with IV antibiotics

  • Any concomitant disease that may require chronic treatment with systemiccorticosteroids or immunosuppressants during the course of the study

  • Contraindications or intolerance to oral or IV corticosteroids, including IVmethylprednisolone, 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 bonemarrow transplantation

  • Treatment with fingolimod/Gilenya®, dimethyl fumarate/Tecfidera®, or similartreatment 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 withany experimental procedure for multiple sclerosis (such as treatment for chroniccerebrospinal 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 Design

Total Participants: 131
Treatment Group(s): 4
Primary Treatment: Lumbar Puncture
Phase: 3
Study Start date:
April 29, 2016
Estimated Completion Date:
April 11, 2023

Connect with a study center

  • University of Alberta Hospital

    Edmonton, Alberta T6G1Z1
    Canada

    Site Not Available

  • University of British Columbia Hospital Site; Djavad Mowafaghian Centre for Brain Health

    Vancouver, British Columbia V6T 1Z3
    Canada

    Site Not Available

  • McGill University; Montreal Neurological Institute; Neurological and Psychiatric

    Montreal, Quebec H3A 2B4
    Canada

    Site Not Available

  • Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden

    Dresden, 01307
    Germany

    Site Not Available

  • Universitätsmedizin Göttingen Georg-August-Universität

    Göttingen, 37075
    Germany

    Site Not Available

  • Karolinska Universitetssjukhuset, Solna

    Stockholm, 113 41
    Sweden

    Site Not Available

  • Stanford University

    Palo Alto, California 94303
    United States

    Site Not Available

  • University of California at San Francisco

    San Francisco, California 94115
    United States

    Site Not Available

  • University Of Colorado

    Aurora, Colorado 80045
    United States

    Site Not Available

  • Yale University School of Medicine ; Pulmonary & Critical Care

    New Haven, Connecticut 06510
    United States

    Site Not Available

  • University of Massachusetts Medical School

    Worcester, Massachusetts 01655
    United States

    Site Not Available

  • Washington University; Wash Uni. Sch. Of Med

    Saint Louis, Missouri 63110
    United States

    Site Not Available

  • Empire Neurology, PC

    Latham, New York 12210
    United States

    Site Not Available

  • Weill Cornell MC-NY Presbyter; Dept. of Neurology/Neuroscience, Judith Jaffe Multiple Sclerosis Ctr

    New York, New York 63110
    United States

    Site Not Available

  • University of North Carolina at Chapel Hill

    Chapel Hill, North Carolina 27599
    United States

    Site Not Available

  • Ohio State University

    Columbus, Ohio 43210
    United States

    Site Not Available

  • Oklahoma Medical Research Foundation; MS Center of Excellence

    Oklahoma City, Oklahoma 73104
    United States

    Site Not Available

  • University of Texas Southwestern Medical Center

    Dallas, Texas 75390-0001
    United States

    Site Not Available

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