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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)

This study is currently recruiting participants.
Verified November 2017 by Genentech, Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02688985
First Posted: February 23, 2016
Last Update Posted: November 28, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Genentech, Inc.
  Purpose
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.

Condition Intervention Phase
Relapsing Multiple Sclerorsis Multiple Sclerosis, Primary Progressive Drug: Ocrelizumab Procedure: Lumber Puncture Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, Biomarker Study to Explore the Mechanism of Action of Ocrelizumab and B-Cell Biology in Patients With Relapsing Multiple Sclerosis or Primary Progressive Multiple Sclerosis

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Change From Baseline in Neurofilament Light (NfL) Levels in Cerebrospinal Fluid (CSF) Post-Treatment With Ocrelizumab [ Time Frame: From Baseline to post-treatment (Week 12, 24, or 52 according to randomization) ]
  • Change From Baseline in Number of Cluster of Differentiation (CD) 19+ B-Cells in CSF Post-Treatment with Ocrelizumab [ Time Frame: From Baseline to post-treatment (Week 12, 24, or 52 according to randomization) ]
  • Change From Baseline in Number of CD3+ T-Cells in CSF Post-Treatment With Ocrelizumab [ Time Frame: From Baseline to post-treatment (Week 12, 24, or 52 according to randomization) ]

Secondary Outcome Measures:
  • Percentage of Participants With Anti-Drug Antibodies (ADAs) to Ocrelizumab [ Time Frame: Predose (Hour 0) on Day 1 of Weeks 1, 24, 48; early termination (up to Week 52); every 24 weeks after Week 48 dose for 48 weeks or until B-cell count returns to baseline value or to lower limit of normal range (up to 3.5 years overall) ]
  • Percentage of Participants With Adverse Events [ Time Frame: From baseline up to approximately 3.5 years ]
  • Serum Concentration of Ocrelizumab [ Time Frame: Predose (Hour 0) on Day 1 of Weeks 1,24,48; at Weeks 12, 52; at early termination (up to Week 52); every 24 weeks after Week 48 dose for 48 weeks or until B-cell count returns to baseline value or to lower limit of normal range (up to 3.5 years overall) ]
  • Ocrelizumab Levels in CSF [ Time Frame: Baseline up to Week 52 (detailed timeframe is provided in outcome description) ]
    RMS Cohort (Arms 1, 2, 3): predose (Hour 0) on Week 1 (baseline), at Weeks 12, 24, or 52 (according to randomization); RMS Cohort (Arm 4): Week -12 (pre-treatment baseline), predose (Hour 0) on Week 1 (treatment baseline), Week 12 (optional); PPMS Cohort: predose (Hour 0) on Week 1 (baseline) and Week 52.


Estimated Enrollment: 104
Actual Study Start Date: April 30, 2016
Estimated Study Completion Date: September 30, 2018
Estimated Primary Completion Date: September 30, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RMS Cohort Arm 1: Ocrelizumab + LP at Weeks 1 and 12
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.
Drug: Ocrelizumab
Ocrelizumab will be administered as IV infusion.
Other Name: RO4964913
Procedure: Lumber Puncture
Participants will receive LP as specified in individual arms.
Experimental: RMS Cohort Arm 2: Ocrelizumab + LP at Weeks 1 and 24
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.
Drug: Ocrelizumab
Ocrelizumab will be administered as IV infusion.
Other Name: RO4964913
Procedure: Lumber Puncture
Participants will receive LP as specified in individual arms.
Experimental: RMS Cohort Arm 3: Ocrelizumab + LP at Weeks 1 and 52
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.
Drug: Ocrelizumab
Ocrelizumab will be administered as IV infusion.
Other Name: RO4964913
Procedure: Lumber Puncture
Participants will receive LP as specified in individual arms.
Experimental: RMS Cohort Arm 4: Ocrelizumab + LP at Week -12 and Week 1
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).
Drug: Ocrelizumab
Ocrelizumab will be administered as IV infusion.
Other Name: RO4964913
Procedure: Lumber Puncture
Participants will receive LP as specified in individual arms.
Experimental: PPMS Cohort: Ocrelizumab + LP at Weeks 1 and 52
Participants with PPMS will receive ocrelizumab 600 mg 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.
Drug: Ocrelizumab
Ocrelizumab will be administered as IV infusion.
Other Name: RO4964913
Procedure: Lumber Puncture
Participants will receive LP as specified in individual arms.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 (human immunodeficiency virus [HIV], syphilis, tuberculosis)
  • 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)
  • Known presence or history of other neurologic disorders
  • 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
  • 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
  • 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

  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02688985


Contacts
Contact: Reference Study ID Number: ML29966 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

Locations
United States, California
Stanford University Active, not recruiting
Palo Alto, California, United States, 94305
University of California at San Francisco Active, not recruiting
San Francisco, California, United States, 94115
United States, Colorado
University Of Colorado Recruiting
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale University School of Medicine ; Pulmonary & Critical Care Active, not recruiting
New Haven, Connecticut, United States, 06510
United States, Massachusetts
University of Massachusetts Medical School Active, not recruiting
Worcester, Massachusetts, United States, 01655
United States, Missouri
Washington University Active, not recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
Empire Neurology, PC Active, not recruiting
Latham, New York, United States, 12210
International MS Management Practice Withdrawn
New York, New York, United States, 10019
Weill Cornell MC-NY Presbyter; Dept. of Neurology/Neuroscience, Judith Jaffe Multiple Sclerosis Ctr Active, not recruiting
New York, New York, United States, 63110
United States, North Carolina
University of North Carolina at Chapel Hill Completed
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
United States, Oklahoma
Oklahoma Medical Research Foundation; MS Center of Excellence Recruiting
Oklahoma City, Oklahoma, United States, 73104
United States, Texas
University of Texas Southwestern Medical Center Active, not recruiting
Dallas, Texas, United States, 75390
Canada, Alberta
University of Alberta Hospital Withdrawn
Edmonton, Alberta, Canada, T6G1Z1
Canada, British Columbia
University of British Columbia Hospital Site; Djavad Mowafaghian Centre for Brain Health Active, not recruiting
Vancouver, British Columbia, Canada, V6T 1Z3
Canada, Quebec
McGill University; Montreal Neurological Institute; Neurological and Psychiatric Recruiting
Montreal, Quebec, Canada, H3A 2B4
Germany
Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden Recruiting
Dresden, Germany, 01307
Universitätsmedizin Göttingen Georg-August-Universität Recruiting
Göttingen, Germany, 37075
Sweden
Karolinska Universitetssjukhuset, Solna Recruiting
Stockholm, Sweden, 171 76
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT02688985     History of Changes
Other Study ID Numbers: ML29966
2015-004616-37 ( EudraCT Number )
First Submitted: February 18, 2016
First Posted: February 23, 2016
Last Update Posted: November 28, 2017
Last Verified: November 2017

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases