A Study of Ocrelizumab in Participants With Relapsing Remitting Multiple Sclerosis (RRMS) Who Have Had a Suboptimal Response to an Adequate Course of Disease-Modifying Treatment (DMT)

An Open-Label Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Patients With Relapsing Remitting Multiple Sclerosis Who Have Had a Suboptimal Response to an Adequate Course of Disease-Modifying Treatment

This study will evaluate the efficacy and safety of ocrelizumab in participants with RRMS who have had a suboptimal response to an adequate course of DMT. Participants will receive ocrelizumab as an initial dose of two 300-milligrams (mg) intravenous (IV) infusions (600 mg total) separated by 14 days followed by one 600-mg IV infusion for a maximum of 4 doses (up to 96 weeks). Anticipated time on study treatment is 96 weeks.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis, Relapsing-Remitting
• Intervention / Treatment: Drug: Ocrelizumab; Drug: Ocrelizumab

Detailed Description

Participants who complete their Week 72 ocrelizumab infusion and do not experience any serious infusion related reaction (IRR) throughout the main study will be eligible to enroll in an optional, open-label, non-randomized substudy to MN30035 and receive one additional shorter infusion of ocrelizumab at the Week 96 visit. This substudy will enroll approximately 100 patients from MN30035 main study.

• Study Type: Interventional
• Enrollment (Actual): 608
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1J 1Z4
    • Chu de Quebec Universite Laval
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Centre; Centre Dept of Medical Clinical Neuroscience
    • Edmonton, Alberta, Canada, T6C 2G3
      • University of Alberta; Divison of Pulmonary Medicine, Dept. of Medicine,
  • British Columbia
    • Burnaby, British Columbia, Canada, V5G 2X6
      • Fraser Health Multiple Sclerosis Clinic; Burnaby Hospital Pharmacy
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Horizon Health Network - Multiple Sclerosis Clinic
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 4K4
      • Dalhousie Multiple Sclerosis Research Unit
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton General Hospital
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital - General Campus; Department of Neurology - Multiple Sclerosis
    • Toronto, Ontario, Canada
      • St. Michael's Hospital MS Clinic, MS Research Centre
  • Quebec
    • Gatineau, Quebec, Canada, J8Y 1W2
      • Clinique NeuroOutaouais
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • Recherche Sepmus, Inc.
    • Levis, Quebec, Canada, G6V 3Z1
      • Hopital Hotel Dieu de Levis
    • Montreal, Quebec, Canada, H3A 2B4
      • McGill University; Montreal Neurological Institute; Neurological and Psychiatric
    • Montreal, Quebec, Canada, H2X 0A9
      • Chum Campus Notre Dame
    • Trois Rivieres, Quebec, Canada, G8Z 3R9
      • MS Clinic Mauricie Bois Francs
• United States
  • Alabama
    • Cullman, Alabama, United States, 35058
      • North Central Neurology Associates
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurological Institute
    • Phoenix, Arizona, United States, 85006
      • Phoenix Neurological Associates Ltd
    • Tucson, Arizona, United States, 85704
      • Territory Neurology and Research Institute
  • California
    • Carlsbad, California, United States, 92011
      • The Research Center of Southern California, LLC
    • Carmichael, California, United States, 95608
      • Mercy Medical Group; MS Centre Nurse
    • Fullerton, California, United States, 92835
      • Fullerton Neurology and Headache Center
    • La Jolla, California, United States, 92037
      • Scripps Health
    • San Francisco, California, United States, CA94158
      • UCSF- Multiple Sclerosis Centre; Department of Neurology
    • Torrance, California, United States, 90502
      • Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
  • Colorado
    • Basalt, Colorado, United States, 81621
      • Mountain Neurological Research Center; Roaring Fork Neurologt, P.C.
    • Centennial, Colorado, United States, 80112
      • IMMUNOe Research Centers
    • Englewood, Colorado, United States, 80113
      • Colorado Neurological Institute
    • Fort Collins, Colorado, United States, 80528
      • Advanced Neurology of Colorado, LLC
  • Connecticut
    • Fairfield, Connecticut, United States, 06824
      • Associated Neurologists of Southern CT PC
    • Stamford, Connecticut, United States, 06905
      • KI Health Partners, LLC; New England Institute for Clinical Research
  • Florida
    • Maitland, Florida, United States, 32751
      • Neurology Associates PA
    • Miami, Florida, United States, 33136
      • University of Miami Miller School of Medicine; Clinical Reseach Building
    • Port Charlotte, Florida, United States, 33952
      • Neurostudies Inc
    • Sunrise, Florida, United States, 33351
      • Infinity Clinical Research, LLC
    • Tampa, Florida, United States, 33609
      • Axiom Clinical Research of Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida - Bradenton
  • Georgia
    • Atlanta, Georgia, United States, 30327
      • MS Center of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Hospital
    • Northbrook, Illinois, United States, 60062
      • Consultants in Neurology Ltd
  • Indiana
    • Avon, Indiana, United States, 46123
      • American Health Network Institute, LLC
    • Indianapolis, Indiana, United States, 46256
      • Josephson Wallack Munshower Neurology PC
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center; Division of Nuclear Medicine
  • Kentucky
    • Lexington, Kentucky, United States, 02421
      • Lahey Clinic Med Ctr
    • Lexington, Kentucky, United States, 40513
      • Associates in Neurology PSC
    • Louisville, Kentucky, United States, 40207
      • Community Medical Associates Inc.; d.b.a. Norton Neurology Services MS Services
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center; Department of Neurology
    • Baltimore, Maryland, United States, 21287
      • John Hopkins University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Med Ctr; Neurology/MS Center
    • Wellesley, Massachusetts, United States, 02481
      • Dragonfly Research, LLC
    • Worcester, Massachusetts, United States, 01655
      • UMass Memorial Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University; Department of Neurology
  • Minnesota
    • Golden Valley, Minnesota, United States, 55422
      • Minneapolis Clinic of Neurology
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine; Department of Neurology
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Cleveland Clinic Lou Ruvo; Center for Brain Research
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Rutgers New Jersey Medical School
    • Teaneck, New Jersey, United States, 07666
      • Holy Name Hospital; Institute For Clinical Research
  • New York
    • Buffalo, New York, United States, 14203
      • Jacobs Neurological Institute
    • Latham, New York, United States, 12110
      • The MS Center of Northeastern New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Patchogue, New York, United States, 11772
      • South Shore Neurologic Associates P.C.
    • Plainview, New York, United States, 11803
      • Island Neurological Associates, P.C.
  • North Carolina
    • Raleigh, North Carolina, United States, 27607-6520
      • Raleigh Neurology Associates
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • UC Health Clinical Trials Office
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation; Cleveland Clinic Cancer Center/I40
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Wexner Medical Center; Department of Neurology
    • Dayton, Ohio, United States, 45417
      • Neurology Specialists, Inc
    • Westerville, Ohio, United States, 43081
      • Neurology and Neuroscience Assoc., Inc.
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma Medical Research Foundation
  • Oregon
    • Portland, Oregon, United States, 97225
      • Providence Multiple Sclerosis Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • Allegheny Neurological Associates
  • Tennessee
    • Cordova, Tennessee, United States, 38018
      • Neurology Clinic PC
    • Knoxville, Tennessee, United States, 37922
      • Hope Neurology
  • Texas
    • Houston, Texas, United States, 77030
      • Uni of Texas Health Science Center At Houston
    • Lubbock, Texas, United States, 79410
      • Bhupesh Dihenia M.D. P.A.
    • Round Rock, Texas, United States, 78681
      • Central Texas Neurology Consultants
    • San Antonio, Texas, United States, 78212
      • Neurology Center of San Antonio
  • Utah
    • Salt Lake City, Utah, United States, 84103
      • Rocky Mountain MS Clinic
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Neuroscience Institute
    • Tacoma, Washington, United States, 98405
      • MultiCare Health System Institute for Research and Innovation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of multiple sclerosis (specifically RRMS), in accordance with the revised 2010 McDonald criteria
• Disease duration from first symptom of less than or equal to (</=) 12 years
• Treated with an adequate course of treatment with no more than three prior DMT regimens of greater than or equal to (>/=) 6 months, and the discontinuation of the most recent adequately used DMT was due to suboptimal response
• Suboptimal response while the participant was on his/her last adequately used DMT for >/=6 months (defined by having one of the following qualifying events despite being on a stable dose of the same DMT for at least 6 months: one or more clinically reported relapses, one or more T1 Gd-enhanced lesions, or two or more new or enlarging T2 lesions on MRI); these qualifying events must have occurred while on the last adequately used DMT. In participants receiving stable doses of the same approved DMT for more than a year, the event must have occurred within the last 12 months of treatment with this DMT from the date of screening

Exclusion Criteria:

• History of primary progressive multiple sclerosis (PPMS), progressive relapsing multiple sclerosis (PRMS), or secondary progressive multiple sclerosis (SPMS)
• Contraindications for MRI
• Known presence of other neurological disorders that may mimic multiple sclerosis
• Pregnancy or lactation, or intention to become pregnant during the study
• Requirement for chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
• History of or currently active primary or secondary immunodeficiency
• Lack of peripheral venous access
• History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
• Active infection, or history of or known presence of recurrent or chronic infection such as human immunodeficiency virus (HIV), syphilis, or tuberculosis
• History of progressive multifocal leukoencephalopathy
• Contraindications to or intolerance of oral or IV corticosteroids
• Previous treatment with fingolimod (Gilenya®) or dimethyl fumarate (Tecfidera®) in participants whose lymphocyte count is below the lower limit of normal (LLN)
• Treatment with alemtuzumab (Lemtrada®)
• Previous treatment with systemic cyclophosphamide, azathioprine, mycophenolate mofetil, cyclosporine, or methotrexate
• Previous treatment with natalizumab within 12 months prior to screening unless failure was due to confirmed, persistent anti-drug antibodies (ADAs). Participants previously treated with natalizumab will be eligible for this study only if duration of treatment with natalizumab was less than (<) 1 year and natalizumab was not used in the 12 months prior to screening. Anti-John Cunningham virus (JCV) antibody status (positive or negative) and titer (both assessed within the year of screening) must be documented prior to enrollment
• Treatment with dalfampridine (Ampyra®) unless on stable dose for >/=30 days prior to screening
• Treatment with a B-cell targeted therapies (e.g., rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab)
• Treatment with a drug that is experimental (Exception: treatment with an experimental drug that was subsequently approved in the participant's country is allowed)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ocrelizumab; Participants will receive ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks).	Drug: Ocrelizumab; Participants will receive ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks).; Other Names: RO4964913; Drug: Ocrelizumab; Participants will receive an additional single 600-mg dose IV infusion at a shorter infusion rate (approximately 2 hours instead of 3.5 hours); Other Names: RO4964913
Experimental: Ocrelizumab (substudy); Participants with no serious IRR throughout the main study will be eligible to enroll in an optional substudy and receive one additional shorter infusion of ocrelizumab at the Week 96 visit. Ocrelizumab will be administered IV as a single 600-mg dose at a shorter infusion rate (approximately 2 hours instead of 3.5 hours)	Drug: Ocrelizumab; Participants will receive ocrelizumab as an initial dose of two 300-mg IV infusions (600 mg total) separated by 14 days (on Days 1 and 15) followed by one 600-mg IV infusion every 24 weeks for a maximum of 4 doses (up to 96 weeks).; Other Names: RO4964913; Drug: Ocrelizumab; Participants will receive an additional single 600-mg dose IV infusion at a shorter infusion rate (approximately 2 hours instead of 3.5 hours); Other Names: RO4964913

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Without Any Protocol-Defined Events During 96-Week Period	Protocol-defined event is the occurrence of either protocol-defined relapse (occurrence of new or worsening neurological symptoms attributable to multiple sclerosis) or T1 gadolinium (Gd)-enhanced lesion on brain magnetic resonance imaging (MRI) or new and/or enlarging T2 lesion on brain MRI or confirmed disability progression at 24 weeks.	Baseline up to Week 96
Percentage of Participants With Infusion Related Reactions (IRRs) in Optional Substudy	Rate and frequency of Grade 3 or 4 IRRs with onset on or after the shorter ocrelizumab infusion	Week 96 to Week 100

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Without Any Protocol-Defined Events During 24-Week and 48-Week Period	Protocol-defined event is the occurrence of either protocol-defined relapse (occurrence of new or worsening neurological symptoms attributable to multiple sclerosis) or T1 Gd-enhanced lesion on brain MRI or new and/or enlarging T2 lesion on brain MRI or confirmed disability progression at 24 weeks.	Baseline up to Weeks 24 and 48
Time to Protocol-Defined Event	Protocol-defined event is the occurrence of either protocol-defined relapse (occurrence of new or worsening neurological symptoms attributable to multiple sclerosis) or T1 Gd-enhanced lesion on brain MRI or new and/or enlarging T2 lesion on brain MRI or confirmed disability progression at 24 weeks.	Baseline up to Week 96
Total Number of Protocol-Defined Relapses Per Participant Year During 96-week Period	Protocol-defined relapse is an occurrence of new or worsening neurological symptoms attributable to multiple sclerosis which must persist for greater than (>) 24 hours and should not be attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications) and immediately preceded by a stable or improving neurological state for least 30 days. The Adjusted Annualized Relapse Rate was adjusted by baseline Expanded Disability Status Scale (EDSS <2.5 vs. >=2.5) and number of previous disease-modifying treatments (DMTs =1 vs. >1)	Baseline up to Week 96
Time to Onset of First Protocol-Defined Relapse	Protocol-defined relapse is an occurrence of new or worsening neurological symptoms attributable to multiple sclerosis which must persist for >24 hours and should not be attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications) and immediately preceded by a stable or improving neurological state for least 30 days.	Baseline up to Week 96
Time to Onset of First T1 Gd-Enhanced Lesion as Detected by Brain MRI		Baseline up to Week 96
Time to Onset of First New and/or Enlarging T2 Lesion as Detected by Brain MRI		Baseline up to Week 96
Time to Onset of Confirmed Disability Progression (CDP) for at Least 24 Weeks According to Expanded Disability Status Scale (EDSS) Score		Baseline up to Week 96
Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI	The analyses included participants who had an interpretable MRI at the time point of interest. Participants having 0, 1, 2, 3, and greater than 3 lesions at weeks 24, 48, and 96 were included in the analysis.	Weeks 24, 48, and 96
Change From Baseline in Total T2 Lesion Volume as Detected by Brain MRI	Baseline data is represented as mean; post-Baseline date are represented as mean changes.	Baseline, Weeks 24, 48, and 96
Total Number of New and/or Enlarging T2 Lesions as Detected by Brain MRI		Weeks 24, 48, and 96
Percentage of Participants With Adverse Events	An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.	Baseline up to 100 weeks

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2016
• Primary Completion (Actual): May 3, 2019
• Study Completion (Actual): May 3, 2019

Study Registration Dates

• First Submitted: December 18, 2015
• First Submitted That Met QC Criteria: December 18, 2015
• First Posted (Estimate): December 22, 2015

Study Record Updates

• Last Update Posted (Actual): May 26, 2020
• Last Update Submitted That Met QC Criteria: May 8, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Immunologic Factors; Ocrelizumab
• Other Study ID Numbers: MN30035

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No