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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: NCT02861014
Recruitment Status : Completed
First Posted : August 10, 2016
Results First Posted : February 3, 2021
Last Update Posted : March 26, 2021
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE August 5, 2016
First Posted Date  ICMJE August 10, 2016
Results First Submitted Date  ICMJE October 13, 2020
Results First Posted Date  ICMJE February 3, 2021
Last Update Posted Date March 26, 2021
Actual Study Start Date  ICMJE September 9, 2016
Actual Primary Completion Date October 25, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 13, 2021)
Percentage of Participants With No Evidence of Disease Activity (NEDA) as Per Protocol Defined Events During a 96-Week Period [ Time Frame: Week 96 ]
A protocol-defined event of disease activity was defined by the occurrence of at least one of the following while on treatment with ocrelizumab:
  • A protocol-defined relapse (PDR)
  • 24-week CDP based on increase in EDSS while on treatment with ocrelizumab
  • A T1 Gd-enhanced lesion after Week 8
  • A new and/or enlarging T2 hyperintense lesion on MRI after Week 8 compared to the Week 8 MRI scan
Original Primary Outcome Measures  ICMJE
 (submitted: August 5, 2016)
Percentage of Participants With No Evidence of Disease Activity (NEDA) as Per Protocol Defined Events During a 96-Week Period [ Time Frame: 96 weeks ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 13, 2021)
  • Percentage of Participants Free From a Protocol-Defined Event of Disease Activity During 24 Weeks Period [ Time Frame: Baseline up to 24 weeks ]
    A protocol-defined event of disease activity was defined by the occurrence of at least one of the following while on treatment with ocrelizumab:
    • A protocol-defined relapse (PDR)
    • 24-week CDP based on increase in EDSS while on treatment with ocrelizumab
    • A T1 Gd-enhanced lesion after Week 8
    • A new and/or enlarging T2 hyperintense lesion on MRI after Week 8 compared to the Week 8 MRI scan
  • Percentage of Participants Free From a Protocol-Defined Event of Disease Activity During 48 Weeks Period [ Time Frame: Baseline up to 48 weeks ]
    A protocol-defined event of disease activity was defined by the occurrence of at least one of the following while on treatment with ocrelizumab:
    • A protocol-defined relapse (PDR)
    • 24-week CDP based on increase in EDSS while on treatment with ocrelizumab
    • A T1 Gd-enhanced lesion after Week 8
    • A new and/or enlarging T2 hyperintense lesion on MRI after Week 8 compared to the Week 8 MRI scan
  • Time to First Protocol-Defined Event of Disease Activity [ Time Frame: Baseline up to 96 Weeks ]
    The definition of a protocol-defined event of disease activity is the occurrence of at least one of the following while on treatment with ocrelizumab:
    • A protocol-defined relapse defined as: Symptoms must persist for >24 hours and should not be attributable to confounding clinical factors; Symptoms should be preceded by neurological stability for at least 30 days; Symptoms should be accompanied by new objective neurological worsening determined with a timely EDSS/ Functional Systems Score (FSS) assessment
    • 24 weeks confirmed disability progression based on increases in EDSS while on treatment with ocrelizumab
    • A T1 Gd-enhanced lesion after Week 8
    • A new and/or enlarging T2 hyperintense lesion on MRI after Week 8 compared to the Week 8 MRI scan.
  • Change From Baseline to Week 96 in Expanded Disability Status Scale (EDSS) [ Time Frame: Baseline, Weeks: 24, 48, 72, 96 ]
    The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.
  • Absolute Change From Baseline in EDSS Category at Week 96 [ Time Frame: Up to Week 96 ]
    The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.
  • Percentage of Participants With a Baseline EDSS Score ≥2 With CDI at Week 96 [ Time Frame: Week 96 ]
    The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.
  • Annualized Protocol-defined Relapse Rate at Week 96 [ Time Frame: Week 96 ]
  • Time to Onset of 24-week Confirmed Disability Progression [ Time Frame: Baseline up to 96 Weeks ]
  • Time to Onset of First Protocol-Defined Relapse [ Time Frame: Baseline up to 96 Weeks ]
    A protocol-defined multiple sclerosis (MS) relapse is an occurrence of new or worsening neurological symptoms attributable to MS that meets the following criteria:
    • Symptoms must persist for >24 hours and should not be attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications)
    • Symptoms should be preceded by neurological stability for at least 30 days
    • Symptoms should be accompanied by new objective neurological worsening determined with a timely EDSS/ Functional Systems Score (FSS) assessment, consistent with an increase of at least:
      • ≥ 0.5 points on EDSS scale
      • or ≥ 2 points on one of the following FSS scales: pyramidal, ambulation, cerebellar, brainstem, sensory, or visual
      • or ≥ 1 point on two or more of the following FSS scales: pyramidal, ambulation, cerebellar, brainstem, sensory, or visual
  • Time to Onset of First New and/or Enlarging T2 Lesion [ Time Frame: Baseline up to 96 Weeks ]
  • Mean Number of T1 Gd-enhancing Lesions Per MRI Scan at Weeks 24, 48 and 96 [ Time Frame: Weeks: 24, 48, 96 ]
    Mean number of T1 Gd-enhancing lesions per MRI scan: Total number of T1 Gd-enhanced lesions divided by the total number of interpretable MRI scans
  • Change From Baseline to Week 96 in Total T2 Lesion Volume Detected by Brain MRI From [ Time Frame: Baseline, Week 96 ]
  • Percentage Change From Baseline to Week 96 in Total T2 Lesion Volume Detected by Brain MRI [ Time Frame: Baseline, Week 96 ]
  • Volume of New and/or Enlarging T2 Hyperintense Lesions Volume of Lesions Per MRI Scan at Weeks 24, 48, 96 [ Time Frame: Weeks 24, 48, 96 ]
    The number of new and/or enlarging T2 lesions at week 24, 48 and 96 is calculated as the sum of the individual number of new and/or enlarging lesions at each visit. Data from other unscheduled assessments is included in this summary or analysis.
  • Mean Number of New and/or Enlarging T2 Hyperintense Lesions Per MRI Scan [ Time Frame: Weeks 24, 48, 96 ]
    Mean number of new and/or enlarging T2 hyperintense lesions per MRI scan: Total number of new and/or enlarging T2 hyperintense lesions divided by the total number of interpretable MRI scans
  • Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume [ Time Frame: Weeks 48, 96 ]
  • Percentage Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume [ Time Frame: Weeks 48, 96 ]
  • Adjusted Mean Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume [ Time Frame: Weeks 48, 96 ]
  • Adjusted Mean Percentage Change From Baseline in Brain Volume [ Time Frame: Weeks 24, 48, 96 ]
  • Adjusted Mean Percentage Change From Baseline in Cortical Grey Matter Volume [ Time Frame: Weeks 48, 96 ]
  • Adjusted Mean Percentage Change From Baseline in White Matter Volume [ Time Frame: Weeks 48, 96 ]
  • Mean Change From Baseline in Cognitive Performance (Processing Speed/Working Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Symbol Digit Modalities Test (SDMT) Score [ Time Frame: Baseline, Weeks: 48, 96 ]
    Brief International Cognitive Assessment for MS (BICAMS) is assessing cognitive processing speed and verbal and visual memory. Symbol Digits Modalities Test (SDMT) is assessing processing speed/working memory. The SDMT presents a series of nine symbols, each paired with a single digit in a key at the top of a standard sheet of paper. Participants are asked to voice the digit associated with each symbol as rapidly as possible for 90 sec. There is a single outcome measure - the number correct over the 90 sec time span. The higher the results, the better processing speed/working memory.
  • Change From Baseline in Cognitive Performance (Visuospatial Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Brief Visuospatial Memory Test-Revised (BVMT-R) Score [ Time Frame: Baseline, Weeks 48, 96 ]
    Brief International Cognitive Assessment for MS (BICAMS) is assessing cognitive processing speed and verbal and visual memory. Brief Visuospatial Memory Test-Revised (BVMT-R) is assessing visuospatial memory. In this test, six abstract designs are presented for 10 sec. The display is removed from view and patients render the stimuli via pencil on paper manual responses. Each design receives from 0 to 2 points representing accuracy and location. There are three learning trials, and the outcome measure is the total number of points earned over the three learning trials, thus the scale range is 0-36. The higher the result, the better visual/spatial memory.
  • Percentage Change From Baseline in Cognitive Performance (Processing Speed/Working Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Symbol Digit Modalities Test (SDMT) Score [ Time Frame: Baseline, Weeks 48, 96 ]
    Brief International Cognitive Assessment for MS (BICAMS) is assessing cognitive processing speed and verbal and visual memory. Symbol Digits Modalities Test (SDMT) is assessing processing speed/working memory. The SDMT presents a series of nine symbols, each paired with a single digit in a key at the top of a standard sheet of paper. Participants are asked to voice the digit associated with each symbol as rapidly as possible for 90 sec. There is a single outcome measure - the number correct over the 90 sec time span.
  • Percentage Change From Baseline in Cognitive Performance (Visuospatial Memory) at Week 48 and Week 96 as Measured by the Brief International Cognitive Assessment for MS - Brief Visuospatial Memory Test-Revised (BVMT-R) Score [ Time Frame: Baseline, Weeks: 48, 96 ]
    Brief International Cognitive Assessment for MS (BICAMS) is assessing cognitive processing speed and verbal and visual memory. Brief Visuospatial Memory Test-Revised (BVMT-R) is assessing visuospatial memory. In this test, six abstract designs are presented for 10 sec. The display is removed from view and patients render the stimuli via pencil on paper manual responses. Each design receives from 0 to 2 points representing accuracy and location. There are three learning trials, and the outcome measure is the total number of points earned over the three learning trials, thus the scale range is 0-36. The higher the result, the better visual/spatial memory.
  • Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to to 96 weeks after the end of the Treatment Period ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 5, 2016)
  • Percentage of Participants Free From a Protocol-Defined Event of Disease Activity During 24 and 48 Weeks Period [ Time Frame: Baseline up to 24 weeks, Baseline up to 48 weeks ]
  • Time to First Protocol-Defined Event of Disease Activity [ Time Frame: Baseline up to Week 96 ]
  • Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Week 96 [ Time Frame: Baseline, Week 96 ]
  • Percentage of Participants With Confirmed Disability Improvement (CDI), Confirmed Disability Progression (CDP), or Stable Disability, as Assessed Using EDSS Scale [ Time Frame: Up to Week 96 ]
  • Annualized Rate of Protocol-Defined Relapses [ Time Frame: Week 96 ]
  • Time to Onset of First Protocol-Defined Relapse [ Time Frame: Up to Week 96 ]
  • Time to Onset of 24 Weeks Confirmed Disability Progression (CDP), as Assessed Using EDSS Scale [ Time Frame: Up to Week 96 ]
  • Time to Onset of First New and/or Enlarging T2 Lesion Detected by Brain Magnetic Resonance Imaging (MRI) [ Time Frame: Up to Week 96 ]
  • Total Number of T1 Gadolinium-Enhanced Lesions Detected by Brain MRI [ 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 ]
  • Change From Baseline in Volume of T1 Hypointense Lesions Detected by Brain MRI at Weeks 24, 48, and 96 [ Time Frame: Baseline, Weeks 24, 48, and 96 ]
  • Change From Baseline in Number of T1 Hypointense Lesions Detected by Brain MRI at Weeks 24, 48, and 96 [ Time Frame: Baseline, Weeks 24, 48, and 96 ]
  • Change From Baseline in Brain Volume Detected by Brain MRI at Weeks 24, 48, and 96 [ Time Frame: Baseline, Weeks 24, 48, and 96 ]
  • Change From Baseline in Cognitive Performance at Week 48 and 96 as Measured by Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) Battery [ Time Frame: Baseline, Weeks 48 and 96 ]
  • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to approximately 4.5 years ]
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 Efficacy and Safety of Ocrelizumab in Patients With Relapsing Multiple Sclerosis Who Have A Suboptimal Response to an Adequate Course of Disease-Modifying Treatment
Brief Summary The purpose of this prospective, multicenter, open-label, efficacy, and safety study is to assess the efficacy and safety of ocrelizumab in participants with Relapsing Remitting Multiple Sclerosis (RRMS) who have had a suboptimal response to an adequate course of a Disease-Modifying Treatment (DMT). The study will consist of a Screening period (up to 4 weeks), an Open-label treatment period (96 weeks; with last dose administered at Week 72), and a Follow-up period of at least 2 years.
Detailed Description Not Provided
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 Biological: Ocrelizumab
Ocrelizumab will be administered as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Other Name: RO4964913
Study Arms  ICMJE Experimental: Ocrelizumab
Ocrelizumab will be administered as two 300 mg IV infusions on Days 1 and 15 followed by one 600 mg IV infusions administered at Weeks 24, 48, and 72.
Intervention: Biological: 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: July 31, 2017)
681
Original Estimated Enrollment  ICMJE
 (submitted: August 5, 2016)
600
Actual Study Completion Date  ICMJE December 15, 2020
Actual Primary Completion Date October 25, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Have a definite diagnosis of RRMS, confirmed as per the revised McDonald 2010 criteria
  • Have a length of disease duration, from first symptom, of less than (<) 10 years
  • Have received no more than two prior DMTs, and the discontinuation of the most recent DMT was due to lack of efficacy
  • Suboptimal disease control while on a DMT
  • Expanded Disability Status Scale (EDSS) of 0.0 to 4.0, inclusive, at Screening
  • For women of childbearing potential: agreement to use an acceptable birth control method during the treatment period and for at least 6 months after the last dose of study drug

Exclusion Criteria:

  • Secondary progressive multiple sclerosis (SPMS) or history of primary progressive or progressive relapsing multiple sclerosis (MS)
  • Inability to complete an Magnetic Resonance Imaging (MRI) procedure
  • Known presence of other neurological disorders
  • Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
  • History or currently active primary or secondary immunodeficiency
  • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies
  • History of opportunistic infections
  • History or known presence of recurrent or chronic infection
  • History of malignancy
  • Congestive heart failure
  • Known active bacterial, viral, fungal, mycobacterial infection or other infection, excluding fungal infection of nail beds
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 Australia,   Belgium,   Czechia,   Denmark,   Estonia,   Finland,   France,   Germany,   Ireland,   Italy,   Netherlands,   Norway,   Spain,   Sweden,   Switzerland,   Turkey,   United Kingdom
Removed Location Countries Czech Republic,   Hong Kong
 
Administrative Information
NCT Number  ICMJE NCT02861014
Other Study ID Numbers  ICMJE MA30005
2015-005597-38 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date March 2021

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