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)

• ClinicalTrials.gov Identifier: NCT02637856
• Recruitment Status: Completed
• First Posted: December 22, 2015
• Results First Posted: May 26, 2020
• Last Update Posted: May 26, 2020
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Multiple Sclerosis, Relapsing-Remitting	Drug: Ocrelizumab	Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 608 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: February 11, 2016
• Actual Primary Completion Date: May 3, 2019
• Actual Study Completion Date: May 3, 2019

Arms and Interventions

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 Name: 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 an additional single 600-mg dose IV infusion at a shorter infusion rate (approximately 2 hours instead of 3.5 hours); Other Name: RO4964913

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants Without Any Protocol-Defined Events During 96-Week Period [ Time Frame: Baseline up to Week 96 ]
   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.
2. Percentage of Participants With Infusion Related Reactions (IRRs) in Optional Substudy [ Time Frame: Week 96 to Week 100 ]
   Rate and frequency of Grade 3 or 4 IRRs with onset on or after the shorter ocrelizumab infusion

Secondary Outcome Measures :

1. Percentage of Participants Without Any Protocol-Defined Events During 24-Week and 48-Week Period [ Time Frame: Baseline up to Weeks 24 and 48 ]
   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.
2. Time to Protocol-Defined Event [ Time Frame: Baseline up to Week 96 ]
   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.
3. Total Number of Protocol-Defined Relapses Per Participant Year During 96-week Period [ Time Frame: Baseline up to Week 96 ]
   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)
4. Time to Onset of First Protocol-Defined Relapse [ Time Frame: Baseline up to Week 96 ]
   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.
5. Time to Onset of First T1 Gd-Enhanced Lesion as Detected by Brain MRI [ Time Frame: Baseline up to Week 96 ]
6. Time to Onset of First New and/or Enlarging T2 Lesion as Detected by Brain MRI [ Time Frame: Baseline up to Week 96 ]
7. Time to Onset of Confirmed Disability Progression (CDP) for at Least 24 Weeks According to Expanded Disability Status Scale (EDSS) Score [ Time Frame: Baseline up to Week 96 ]
8. Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI [ Time Frame: Weeks 24, 48, and 96 ]
   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.
9. Change From Baseline in Total T2 Lesion Volume as Detected by Brain MRI [ Time Frame: Baseline, Weeks 24, 48, and 96 ]
   Baseline data is represented as mean; post-Baseline date are represented as mean changes.
10. Total Number of New and/or Enlarging T2 Lesions as Detected by Brain MRI [ Time Frame: Weeks 24, 48, and 96 ]
11. Percentage of Participants With Adverse Events [ Time Frame: Baseline up to 100 weeks ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 55 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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)

Contacts and Locations

Locations

United States, Alabama

North Central Neurology Associates

Cullman, Alabama, United States, 35058

United States, Arizona

Phoenix Neurological Associates Ltd

Phoenix, Arizona, United States, 85006

Barrow Neurological Institute

Phoenix, Arizona, United States, 85013

Territory Neurology and Research Institute

Tucson, Arizona, United States, 85704

United States, California

The Research Center of Southern California, LLC

Carlsbad, California, United States, 92011

Mercy Medical Group; MS Centre Nurse

Carmichael, California, United States, 95608

Fullerton Neurology and Headache Center

Fullerton, California, United States, 92835

Scripps Health

La Jolla, California, United States, 92037

UCSF- Multiple Sclerosis Centre; Department of Neurology

San Francisco, California, United States, CA94158

Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center

Torrance, California, United States, 90502

United States, Colorado

Mountain Neurological Research Center; Roaring Fork Neurologt, P.C.

Basalt, Colorado, United States, 81621

IMMUNOe Research Centers

Centennial, Colorado, United States, 80112

Colorado Neurological Institute

Englewood, Colorado, United States, 80113

Advanced Neurology of Colorado, LLC

Fort Collins, Colorado, United States, 80528

United States, Connecticut

Associated Neurologists of Southern CT PC

Fairfield, Connecticut, United States, 06824

KI Health Partners, LLC; New England Institute for Clinical Research

Stamford, Connecticut, United States, 06905

United States, Florida

Neurology Associates PA

Maitland, Florida, United States, 32751

University of Miami Miller School of Medicine; Clinical Reseach Building

Miami, Florida, United States, 33136

Neurostudies Inc

Port Charlotte, Florida, United States, 33952

Infinity Clinical Research, LLC

Sunrise, Florida, United States, 33351

Axiom Clinical Research of Florida

Tampa, Florida, United States, 33609

University of South Florida - Bradenton

Tampa, Florida, United States, 33612

United States, Georgia

Ms Center Of Atlanta

Atlanta, Georgia, United States, 30327

United States, Illinois

University of Chicago Hospital

Chicago, Illinois, United States, 60637

Consultants in Neurology Ltd

Northbrook, Illinois, United States, 60062

United States, Indiana

American Health Network Institute, LLC

Avon, Indiana, United States, 46123

Josephson Wallack Munshower Neurology PC

Indianapolis, Indiana, United States, 46256

United States, Kansas

University of Kansas Medical Center; Division of Nuclear Medicine

Kansas City, Kansas, United States, 66160

United States, Kentucky

Lahey Clinic Med Ctr

Lexington, Kentucky, United States, 02421

Associates in Neurology PSC

Lexington, Kentucky, United States, 40513

Community Medical Associates Inc.; d.b.a. Norton Neurology Services MS Services

Louisville, Kentucky, United States, 40207

United States, Louisiana

Ochsner Clinic Foundation

New Orleans, Louisiana, United States, 70121

United States, Maryland

University of Maryland Medical Center; Department of Neurology

Baltimore, Maryland, United States, 21201

John Hopkins University School of Medicine

Baltimore, Maryland, United States, 21287

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Beth Israel Deaconess Med Ctr; Neurology/MS Center

Boston, Massachusetts, United States, 02215

Dragonfly Research, LLC

Wellesley, Massachusetts, United States, 02481

UMASS Memorial Medical Center

Worcester, Massachusetts, United States, 01655

United States, Michigan

Wayne State University; Department of Neurology

Detroit, Michigan, United States, 48201

United States, Minnesota

Minneapolis Clinic of Neurology

Golden Valley, Minnesota, United States, 55422

United States, Missouri

Washington University School of Medicine; Department of Neurology

Saint Louis, Missouri, United States, 63110

United States, Nevada

Cleveland Clinic Lou Ruvo; Center for Brain Research

Las Vegas, Nevada, United States, 89106

United States, New Jersey

Rutgers New Jersey Medical School

Newark, New Jersey, United States, 07103

Holy Name Hospital; Institute For Clinical Research

Teaneck, New Jersey, United States, 07666

United States, New York

Jacobs Neurological Institute

Buffalo, New York, United States, 14203

The MS Center of Northeastern New York

Latham, New York, United States, 12110

Columbia University Medical Center

New York, New York, United States, 10032

South Shore Neurologic Associates P.C.

Patchogue, New York, United States, 11772

Island Neurological Associates, P.C.

Plainview, New York, United States, 11803

United States, North Carolina

Raleigh Neurology Associates

Raleigh, North Carolina, United States, 27607-6520

United States, Ohio

UC Health Clinical Trials Office

Cincinnati, Ohio, United States, 45267

Cleveland Clinic Foundation; Cleveland Clinic Cancer Center/I40

Cleveland, Ohio, United States, 44195

The Ohio State University Wexner Medical Center; Department of Neurology

Columbus, Ohio, United States, 43210

Neurology Specialists, Inc

Dayton, Ohio, United States, 45417

Neurology and Neuroscience Assoc., Inc.

Westerville, Ohio, United States, 43081

United States, Oklahoma

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, United States, 73104

United States, Oregon

Providence Multiple Sclerosis Center

Portland, Oregon, United States, 97225

United States, Pennsylvania

Allegheny Neurological Associates

Pittsburgh, Pennsylvania, United States, 15212

United States, Tennessee

Neurology Clinic PC

Cordova, Tennessee, United States, 38018

Hope Neurology

Knoxville, Tennessee, United States, 37922

United States, Texas

Uni of Texas Health Science Center At Houston

Houston, Texas, United States, 77030

Bhupesh Dihenia M.D. P.A.

Lubbock, Texas, United States, 79410

Central Texas Neurology Consultants

Round Rock, Texas, United States, 78681

Neurology Center of San Antonio

San Antonio, Texas, United States, 78212

United States, Utah

Rocky Mountain MS Clinic

Salt Lake City, Utah, United States, 84103

United States, Washington

Swedish Neuroscience Institute

Seattle, Washington, United States, 98122

MultiCare Health System Institute for Research and Innovation

Tacoma, Washington, United States, 98405

Canada, Alberta

Foothills Medical Centre; Centre Dept of Medical Clinical Neuroscience

Calgary, Alberta, Canada, T2N 2T9

University of Alberta; Divison of Pulmonary Medicine, Dept. of Medicine,

Edmonton, Alberta, Canada, T6C 2G3

Canada, British Columbia

Fraser Health Multiple Sclerosis Clinic; Burnaby Hospital Pharmacy

Burnaby, British Columbia, Canada, V5G 2X6

Canada, New Brunswick

Horizon Health Network - Multiple Sclerosis Clinic

Saint John, New Brunswick, Canada, E2L 4L2

Canada, Nova Scotia

Dalhousie Multiple Sclerosis Research Unit

Halifax, Nova Scotia, Canada, B3H 4K4

Canada, Ontario

Hamilton General Hospital

Hamilton, Ontario, Canada, L8L 2X2

The Ottawa Hospital - General Campus; Department of Neurology - Multiple Sclerosis

Ottawa, Ontario, Canada, K1H 8L6

St. Michael's Hospital MS Clinic, MS Research Centre

Toronto, Ontario, Canada

Canada, Quebec

Clinique NeuroOutaouais

Gatineau, Quebec, Canada, J8Y 1W2

Recherche Sepmus, Inc.

Greenfield Park, Quebec, Canada, J4V 2J2

Hopital Hotel Dieu de Levis

Levis, Quebec, Canada, G6V 3Z1

Chum Campus Notre Dame

Montreal, Quebec, Canada, H2X 0A9

McGill University; Montreal Neurological Institute; Neurological and Psychiatric

Montreal, Quebec, Canada, H3A 2B4

MS Clinic Mauricie Bois Francs

Trois Rivieres, Quebec, Canada, G8Z 3R9

Canada

CHU De Quebec Universite Laval

Quebec, Canada, G1J 1Z4

Sponsors and Collaborators

Genentech, Inc.

Investigators

• Study Director: Clinical Trials; Hoffmann-La Roche

  Study Documents (Full-Text)

Documents provided by Genentech, Inc.:

Study Protocol  [PDF] June 19, 2018

Statistical Analysis Plan  [PDF] April 30, 2019

More Information

• Responsible Party: Genentech, Inc.
• ClinicalTrials.gov Identifier: NCT02637856
• Other Study ID Numbers: MN30035
• First Posted: December 22, 2015
• Results First Posted: May 26, 2020
• Last Update Posted: May 26, 2020
• Last Verified: May 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Ocrelizumab; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Immunologic Factors; Physiological Effects of Drugs