Clinical trial NCT02637856: 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)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Multiple Sclerosis, Relapsing-Remitting
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2015-12-22
Enrollment: 608
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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)

Primary outcomes:
measure: Percentage of Participants Without Any Protocol-Defined Events During 96-Week Period
timeFrame: Baseline up to Week 96
measure: Percentage of Participants With Infusion Related Reactions (IRRs) in Optional Substudy
timeFrame: Week 96 to Week 100
Secondary outcomes:
measure: Percentage of Participants Without Any Protocol-Defined Events During 24-Week and 48-Week Period
timeFrame: Baseline up to Weeks 24 and 48
measure: Time to Protocol-Defined Event
timeFrame: Baseline up to Week 96
measure: Total Number of Protocol-Defined Relapses Per Participant Year During 96-week Period
timeFrame: Baseline up to Week 96
measure: Time to Onset of First Protocol-Defined Relapse
timeFrame: Baseline up to Week 96
measure: Time to Onset of First T1 Gd-Enhanced Lesion as Detected by Brain MRI
timeFrame: Baseline up to Week 96
measure: Time to Onset of First New and/or Enlarging T2 Lesion as Detected by Brain MRI
timeFrame: Baseline up to Week 96
measure: Time to Onset of Confirmed Disability Progression (CDP) for at Least 24 Weeks According to Expanded Disability Status Scale (EDSS) Score
timeFrame: Baseline up to Week 96
measure: Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI
timeFrame: Weeks 24, 48, and 96
measure: Change From Baseline in Total T2 Lesion Volume as Detected by Brain MRI
timeFrame: Baseline, Weeks 24, 48, and 96
measure: Total Number of New and/or Enlarging T2 Lesions as Detected by Brain MRI
timeFrame: Weeks 24, 48, and 96
measure: Percentage of Participants With Adverse Events
timeFrame: Baseline up to 100 weeks
Other outcomes:
Locations:
city: Cullman
country: United States
facility: North Central Neurology Associates
state: Alabama
city: Phoenix
country: United States
facility: Phoenix Neurological Associates Ltd
state: Arizona
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
city: Tucson
country: United States
facility: Territory Neurology and Research Institute
state: Arizona
city: Carlsbad
country: United States
facility: The Research Center of Southern California, LLC
state: California
city: Carmichael
country: United States
facility: Mercy Medical Group; MS Centre Nurse
state: California
city: Fullerton
country: United States
facility: Fullerton Neurology and Headache Center
state: California
city: La Jolla
country: United States
facility: Scripps Health
state: California
city: San Francisco
country: United States
facility: UCSF- Multiple Sclerosis Centre; Department of Neurology
state: California
city: Torrance
country: United States
facility: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
state: California
city: Basalt
country: United States
facility: Mountain Neurological Research Center; Roaring Fork Neurologt, P.C.
state: Colorado
city: Centennial
country: United States
facility: IMMUNOe Research Centers
state: Colorado
city: Englewood
country: United States
facility: Colorado Neurological Institute
state: Colorado
city: Fort Collins
country: United States
facility: Advanced Neurology of Colorado, LLC
state: Colorado
city: Fairfield
country: United States
facility: Associated Neurologists of Southern CT PC
state: Connecticut
city: Stamford
country: United States
facility: KI Health Partners, LLC; New England Institute for Clinical Research
state: Connecticut
city: Maitland
country: United States
facility: Neurology Associates PA
state: Florida
city: Miami
country: United States
facility: University of Miami Miller School of Medicine; Clinical Reseach Building
state: Florida
city: Port Charlotte
country: United States
facility: Neurostudies Inc
state: Florida
city: Sunrise
country: United States
facility: Infinity Clinical Research, LLC
state: Florida
city: Tampa
country: United States
facility: Axiom Clinical Research of Florida
state: Florida
city: Tampa
country: United States
facility: University of South Florida - Bradenton
state: Florida
city: Atlanta
country: United States
facility: Ms Center Of Atlanta
state: Georgia
city: Chicago
country: United States
facility: University of Chicago Hospital
state: Illinois
city: Northbrook
country: United States
facility: Consultants in Neurology Ltd
state: Illinois
city: Avon
country: United States
facility: American Health Network Institute, LLC
state: Indiana
city: Indianapolis
country: United States
facility: Josephson Wallack Munshower Neurology PC
state: Indiana
city: Kansas City
country: United States
facility: University of Kansas Medical Center; Division of Nuclear Medicine
state: Kansas
city: Lexington
country: United States
facility: Lahey Clinic Med Ctr
state: Kentucky
city: Lexington
country: United States
facility: Associates in Neurology PSC
state: Kentucky
city: Louisville
country: United States
facility: Community Medical Associates Inc.; d.b.a. Norton Neurology Services MS Services
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center; Department of Neurology
state: Maryland
city: Baltimore
country: United States
facility: John Hopkins University School of Medicine
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Med Ctr; Neurology/MS Center
state: Massachusetts
city: Wellesley
country: United States
facility: Dragonfly Research, LLC
state: Massachusetts
city: Worcester
country: United States
facility: UMASS Memorial Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University; Department of Neurology
state: Michigan
city: Golden Valley
country: United States
facility: Minneapolis Clinic of Neurology
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine; Department of Neurology
state: Missouri
city: Las Vegas
country: United States
facility: Cleveland Clinic Lou Ruvo; Center for Brain Research
state: Nevada
city: Newark
country: United States
facility: Rutgers New Jersey Medical School
state: New Jersey
city: Teaneck
country: United States
facility: Holy Name Hospital; Institute For Clinical Research
state: New Jersey
city: Buffalo
country: United States
facility: Jacobs Neurological Institute
state: New York
city: Latham
country: United States
facility: The MS Center of Northeastern New York
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Patchogue
country: United States
facility: South Shore Neurologic Associates P.C.
state: New York
city: Plainview
country: United States
facility: Island Neurological Associates, P.C.
state: New York
city: Raleigh
country: United States
facility: Raleigh Neurology Associates
state: North Carolina
city: Cincinnati
country: United States
facility: UC Health Clinical Trials Office
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation; Cleveland Clinic Cancer Center/I40
state: Ohio
city: Columbus
country: United States
facility: The Ohio State University Wexner Medical Center; Department of Neurology
state: Ohio
city: Dayton
country: United States
facility: Neurology Specialists, Inc
state: Ohio
city: Westerville
country: United States
facility: Neurology and Neuroscience Assoc., Inc.
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Medical Research Foundation
state: Oklahoma
city: Portland
country: United States
facility: Providence Multiple Sclerosis Center
state: Oregon
city: Pittsburgh
country: United States
facility: Allegheny Neurological Associates
state: Pennsylvania
city: Cordova
country: United States
facility: Neurology Clinic PC
state: Tennessee
city: Knoxville
country: United States
facility: Hope Neurology
state: Tennessee
city: Houston
country: United States
facility: Uni of Texas Health Science Center At Houston
state: Texas
city: Lubbock
country: United States
facility: Bhupesh Dihenia M.D. P.A.
state: Texas
city: Round Rock
country: United States
facility: Central Texas Neurology Consultants
state: Texas
city: San Antonio
country: United States
facility: Neurology Center of San Antonio
state: Texas
city: Salt Lake City
country: United States
facility: Rocky Mountain MS Clinic
state: Utah
city: Seattle
country: United States
facility: Swedish Neuroscience Institute
state: Washington
city: Tacoma
country: United States
facility: MultiCare Health System Institute for Research and Innovation
state: Washington
city: Calgary
country: Canada
facility: Foothills Medical Centre; Centre Dept of Medical Clinical Neuroscience
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta; Divison of Pulmonary Medicine, Dept. of Medicine,
state: Alberta
city: Burnaby
country: Canada
facility: Fraser Health Multiple Sclerosis Clinic; Burnaby Hospital Pharmacy
state: British Columbia
city: Saint John
country: Canada
facility: Horizon Health Network - Multiple Sclerosis Clinic
state: New Brunswick
city: Halifax
country: Canada
facility: Dalhousie Multiple Sclerosis Research Unit
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus; Department of Neurology - Multiple Sclerosis
state: Ontario
city: Toronto
country: Canada
facility: St. Michael's Hospital MS Clinic, MS Research Centre
state: Ontario
city: Gatineau
country: Canada
facility: Clinique NeuroOutaouais
state: Quebec
city: Greenfield Park
country: Canada
facility: Recherche Sepmus, Inc.
state: Quebec
city: Levis
country: Canada
facility: Hopital Hotel Dieu de Levis
state: Quebec
city: Montreal
country: Canada
facility: Chum Campus Notre Dame
state: Quebec
city: Montreal
country: Canada
facility: McGill University; Montreal Neurological Institute; Neurological and Psychiatric
state: Quebec
city: Trois Rivieres
country: Canada
facility: MS Clinic Mauricie Bois Francs
state: Quebec
city: Quebec
country: Canada
facility: CHU De Quebec Universite Laval
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: