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)

Multiple Sclerosis, Relapsing-Remitting Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02637856
• Other study ID #: MN30035
• Status: Completed
• Phase: Phase 3
• Start date: February 11, 2016
• Est. completion date: May 3, 2019

Study information

• Verified date: May 2020
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 608
• Est. completion date: May 3, 2019
• Est. primary completion date: May 3, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

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)

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

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).
• 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)

Locations

Country	Name	City	State
Canada	Fraser Health Multiple Sclerosis Clinic; Burnaby Hospital Pharmacy	Burnaby	British Columbia
Canada	Foothills Medical Centre; Centre Dept of Medical Clinical Neuroscience	Calgary	Alberta
Canada	University of Alberta; Divison of Pulmonary Medicine, Dept. of Medicine,	Edmonton	Alberta
Canada	Clinique NeuroOutaouais	Gatineau	Quebec
Canada	Recherche Sepmus, Inc.	Greenfield Park	Quebec
Canada	Dalhousie Multiple Sclerosis Research Unit	Halifax	Nova Scotia
Canada	Hamilton General Hospital	Hamilton	Ontario
Canada	Hopital Hotel Dieu de Levis	Levis	Quebec
Canada	Chum Campus Notre Dame	Montreal	Quebec
Canada	McGill University; Montreal Neurological Institute; Neurological and Psychiatric	Montreal	Quebec
Canada	The Ottawa Hospital - General Campus; Department of Neurology - Multiple Sclerosis	Ottawa	Ontario
Canada	CHU De Quebec Universite Laval	Quebec
Canada	Horizon Health Network - Multiple Sclerosis Clinic	Saint John	New Brunswick
Canada	St. Michael's Hospital MS Clinic, MS Research Centre	Toronto	Ontario
Canada	MS Clinic Mauricie Bois Francs	Trois Rivieres	Quebec
United States	Ms Center Of Atlanta	Atlanta	Georgia
United States	American Health Network Institute, LLC	Avon	Indiana
United States	John Hopkins University School of Medicine	Baltimore	Maryland
United States	University of Maryland Medical Center; Department of Neurology	Baltimore	Maryland
United States	Mountain Neurological Research Center; Roaring Fork Neurologt, P.C.	Basalt	Colorado
United States	Beth Israel Deaconess Med Ctr; Neurology/MS Center	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Jacobs Neurological Institute	Buffalo	New York
United States	The Research Center of Southern California, LLC	Carlsbad	California
United States	Mercy Medical Group; MS Centre Nurse	Carmichael	California
United States	IMMUNOe Research Centers	Centennial	Colorado
United States	University of Chicago Hospital	Chicago	Illinois
United States	UC Health Clinical Trials Office	Cincinnati	Ohio
United States	Cleveland Clinic Foundation; Cleveland Clinic Cancer Center/I40	Cleveland	Ohio
United States	The Ohio State University Wexner Medical Center; Department of Neurology	Columbus	Ohio
United States	Neurology Clinic PC	Cordova	Tennessee
United States	North Central Neurology Associates	Cullman	Alabama
United States	Neurology Specialists, Inc	Dayton	Ohio
United States	Wayne State University; Department of Neurology	Detroit	Michigan
United States	Colorado Neurological Institute	Englewood	Colorado
United States	Associated Neurologists of Southern CT PC	Fairfield	Connecticut
United States	Advanced Neurology of Colorado, LLC	Fort Collins	Colorado
United States	Fullerton Neurology and Headache Center	Fullerton	California
United States	Minneapolis Clinic of Neurology	Golden Valley	Minnesota
United States	Uni of Texas Health Science Center At Houston	Houston	Texas
United States	Josephson Wallack Munshower Neurology PC	Indianapolis	Indiana
United States	University of Kansas Medical Center; Division of Nuclear Medicine	Kansas City	Kansas
United States	Hope Neurology	Knoxville	Tennessee
United States	Scripps Health	La Jolla	California
United States	Cleveland Clinic Lou Ruvo; Center for Brain Research	Las Vegas	Nevada
United States	The MS Center of Northeastern New York	Latham	New York
United States	Associates in Neurology PSC	Lexington	Kentucky
United States	Lahey Clinic Med Ctr	Lexington	Kentucky
United States	Community Medical Associates Inc.; d.b.a. Norton Neurology Services MS Services	Louisville	Kentucky
United States	Bhupesh Dihenia M.D. P.A.	Lubbock	Texas
United States	Neurology Associates PA	Maitland	Florida
United States	University of Miami Miller School of Medicine; Clinical Reseach Building	Miami	Florida
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Columbia University Medical Center	New York	New York
United States	Rutgers New Jersey Medical School	Newark	New Jersey
United States	Consultants in Neurology Ltd	Northbrook	Illinois
United States	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma
United States	South Shore Neurologic Associates P.C.	Patchogue	New York
United States	Barrow Neurological Institute	Phoenix	Arizona
United States	Phoenix Neurological Associates Ltd	Phoenix	Arizona
United States	Allegheny Neurological Associates	Pittsburgh	Pennsylvania
United States	Island Neurological Associates, P.C.	Plainview	New York
United States	Neurostudies Inc	Port Charlotte	Florida
United States	Providence Multiple Sclerosis Center	Portland	Oregon
United States	Raleigh Neurology Associates	Raleigh	North Carolina
United States	Central Texas Neurology Consultants	Round Rock	Texas
United States	Washington University School of Medicine; Department of Neurology	Saint Louis	Missouri
United States	Rocky Mountain MS Clinic	Salt Lake City	Utah
United States	Neurology Center of San Antonio	San Antonio	Texas
United States	UCSF- Multiple Sclerosis Centre; Department of Neurology	San Francisco	California
United States	Swedish Neuroscience Institute	Seattle	Washington
United States	KI Health Partners, LLC; New England Institute for Clinical Research	Stamford	Connecticut
United States	Infinity Clinical Research, LLC	Sunrise	Florida
United States	MultiCare Health System Institute for Research and Innovation	Tacoma	Washington
United States	Axiom Clinical Research of Florida	Tampa	Florida
United States	University of South Florida - Bradenton	Tampa	Florida
United States	Holy Name Hospital; Institute For Clinical Research	Teaneck	New Jersey
United States	Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center	Torrance	California
United States	Territory Neurology and Research Institute	Tucson	Arizona
United States	Dragonfly Research, LLC	Wellesley	Massachusetts
United States	Neurology and Neuroscience Assoc., Inc.	Westerville	Ohio
United States	UMASS Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Time to Onset of First T1 Gd-Enhanced Lesion as Detected by Brain MRI		Baseline up to Week 96
Secondary	Time to Onset of First New and/or Enlarging T2 Lesion as Detected by Brain MRI		Baseline up to Week 96
Secondary	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
Secondary	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
Secondary	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
Secondary	Total Number of New and/or Enlarging T2 Lesions as Detected by Brain MRI		Weeks 24, 48, and 96
Secondary	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