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Trial record 1 of 1 for:    NCT02637856 | Multiple Sclerosis
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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)

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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:
Information provided by (Responsible Party):
Genentech, Inc.

Tracking Information
First Submitted Date  ICMJE December 18, 2015
First Posted Date  ICMJE December 22, 2015
Results First Submitted Date  ICMJE April 15, 2020
Results First Posted Date  ICMJE May 26, 2020
Last Update Posted Date May 26, 2020
Actual Study Start Date  ICMJE February 11, 2016
Actual Primary Completion Date May 3, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 8, 2020)
  • 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.
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: December 18, 2015)
Percentage of participants Without Any Protocol-defined Events During 96-week Period [ Time Frame: 96 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 8, 2020)
  • 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.
  • 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.
  • 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)
  • 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.
  • Time to Onset of First T1 Gd-Enhanced Lesion as Detected by Brain MRI [ Time Frame: Baseline up to Week 96 ]
  • Time to Onset of First New and/or Enlarging T2 Lesion as Detected by Brain MRI [ Time Frame: 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 [ Time Frame: Baseline up to Week 96 ]
  • 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.
  • 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.
  • Total Number of New and/or Enlarging T2 Lesions as Detected by Brain MRI [ Time Frame: Weeks 24, 48, and 96 ]
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: December 18, 2015)
  • Percentage of participants Without Any Protocol-defined Events During 24-week Period and 48-week Period [ Time Frame: 24 weeks and 48 weeks ]
  • Time to Protocol-defined Event [ Time Frame: 96 weeks ]
  • Annualized Protocol-defined Relapse Rate at Week 96 [ Time Frame: Week 96 ]
  • Time to Onset of First Relapse [ Time Frame: 96 weeks ]
  • Time to Onset of First T1 Gadolinium-enhanced (Gd-enhanced) Lesion [ Time Frame: 96 weeks ]
  • Time to Onset of First New and/or Enlarging T2 Lesion [ Time Frame: 96 weeks ]
  • Time to Onset of Confirmed Disability Progression for at least 24 Weeks [ Time Frame: 96 weeks ]
  • Total Number of T1 Gadolinium-enhancing (Gd-enhancing) Lesions as Detected by Brain MRI at Weeks 24, 48, and 96 [ Time Frame: Weeks 24, 48, and 96 ]
  • Change From Baseline in Total T2 Lesion Volume Detected by Brain MRI at Weeks 24, 48, and 96 [ Time Frame: Baseline, Weeks 24, 48, and 96 ]
  • Total Number of New and/or Enlarging T2 Lesions Detected by Brain MRI at Weeks 24, 48, and 96 [ Time Frame: Weeks 24, 48, and 96 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Sclerosis, Relapsing-Remitting
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • 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).
    Intervention: Drug: Ocrelizumab
  • 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)
    Intervention: Drug: Ocrelizumab
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 8, 2020)
608
Original Estimated Enrollment  ICMJE
 (submitted: December 18, 2015)
600
Actual Study Completion Date  ICMJE May 3, 2019
Actual Primary Completion Date May 3, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 55 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02637856
Other Study ID Numbers  ICMJE MN30035
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Genentech, Inc.
Study Sponsor  ICMJE Genentech, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Genentech, Inc.
Verification Date May 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP