Clinical Trial: Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Participants With Early Stage Relapsing Remitting Multiple Sclerosis (RRMS)

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: An Open-Label, Single-Arm Study to Evaluate the Effectiveness and Safety of Ocrelizumab in Patients With Early Stage Relapsing Remitting Multiple Sclerosis

Brief Summary: This is a prospective, multicenter, open-label, single-arm, phase 3b study which evaluates effectiveness and safety of ocrelizumab in participants with early stage RRMS. The study will consist of an open-label treatment period of 192 weeks and follow-up period of at least 48 weeks.

Detailed Summary:
Sponsor: Hoffmann-La Roche

Current Primary Outcome:

  • Time to Onset of Confirmed Disability Progression (CDP) Sustained fo at Least 24 and 48 Weeks, As Measured Using Expanded Disability Status Scale (EDSS) [ Time Frame: Baseline up to 4 years ]
  • Percentage of Participants With Confirmed Disability Improvement (CDI) at Year 1, As Measured Using EDSS [ Time Frame: Year 1 ]
  • Percentage of Participants With CDP Sustained for At Least 24 and 48 Weeks at Year 1, As Measured Using EDSS [ Time Frame: Year 1 ]
  • Percentage of Participants With CDI at Year 2, As Measured Using EDSS [ Time Frame: Year 2 ]
  • Percentage of Participants With CDP Sustained for At Least 24 and 48 Weeks at Year 2, As Measured Using EDSS [ Time Frame: Year 2 ]
  • Percentage of Participants With CDI at Year 4, As Measured Using EDSS [ Time Frame: Year 4 ]
  • Percentage of Participants With CDP Sustained for At Least 24 and 48 Weeks at Year 4, As Measured Using EDSS [ Time Frame: Year 4 ]
  • Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 1, As Measured Using EDSS [ Time Frame: Year 1 ]
  • Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 2, As Measured Using EDSS [ Time Frame: Year 2 ]
  • Percentage of Participants Who Have Improved, Stable, or Worsened Disability Compared to Baseline at Year 3, As Measured Using EDSS [ Time Frame: Year 3 ]
  • Percentage of Parti

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Percentage of Participants Who Are Relapse Free [ Time Frame: Weeks 48, 96, 144, 192 ]
      Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment.
    • Percentage of Participants With No Evidence of Protocol Defined Disease Activity [ Time Frame: Weeks 96, 144, 192 ]
      Protocol-defined disease activity is defined as having at least one of the following: (1). protocol defined relapse (occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis [MS], as determined using EDSS/Functional Systems Score [FSS] assessment). (2). CDP, as determined using EDSS. (3). a T1 Gd-enhanced lesion after Week 8. (4). a new and/or enlarging T2 hyperintense lesion on magnetic resonance imaging (MRI) after Week 8 compared to the Week 8 MRI scan.
    • Percentage of Participants With no Evidence of Progression (NEP) [ Time Frame: Weeks 96, 192 ]
      NEP is defined as no progression sustained for at least 24 weeks on all of the following three components (CDP; 20 percent [%] increase from baseline in timed 25 Foot Walk Test [T25FWT]; 20% increase from baseline in timed 9 hole peg test [9HPT]). CDP will be assessed using EDSS.
    • Percentage of Participants With no Evidence of Progression Sustained for At Least 24 Weeks and no Active Disease (NEPAD) [ Time Frame: Weeks 96, 192 ]
      NEPAD is defined as no progression on all of the three components of NEP (CDP, T25FWT, 9HPT), no new relapse and no enlarging or new T2 or T1 Gd-enhancing lesion. CDP will be assessed using EDSS. Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment.
    • Change from Baseline in Multiple Sclerosis Functional Composite (MSFC) Total Score [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192 ]
    • Change from Baseline in MSFC Composite (T25FW) Score [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192 ]
    • Change from Baseline in MSFC Composite (9HPT) Score [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192 ]
    • Change from Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192 ]
    • Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI [ Time Frame: Baseline, Weeks 8, 24, 48, 96, 144, 192 ]
    • Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI [ Time Frame: Baseline, Weeks 8, 24, 48, 96, 144, 192 ]
    • Change From Baseline in T1 Volume as Detected by Brain MRI [ Time Frame: Baseline, Weeks 8, 24, 48, 96, 144, 192 ]
    • Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI [ Time Frame: Baseline, Weeks 8, 24, 48, 96, 144, 192 ]
    • Change From Baseline in Brain Volume as Detected by Brain MRI [ Time Frame: Baseline, Weeks 8, 24, 48, 96, 144, 192 ]
    • Time to Treatment Discontinuation [ Time Frame: Baseline up to 4 years ]
    • Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score [ Time Frame: Baseline, Weeks 24, 48, 96, 120, 144, 192 ]
    • SymptoMScreen Composite Score [ Time Frame: Baseline, Weeks 24, 48, 96, 120, 144, 192 ]
    • Quality of Life: Multiple Sclerosis Impact Scale (MSIS)-29 Questionnaire Score [ Time Frame: Baseline, Weeks 24, 48, 96, 120, 144, 192 ]
    • Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 4 years ]
      Short term safety related to the infusion (infusion-related reactions [IRRs], during infusion and up to 24h after) the overall safety is measured continuously at clinical visits and including every 8 week telephone visits up to 48 weeks post study.


    Original Secondary Outcome:

    • Percentage of Participants Who Are Relapse Free [ Time Frame: Weeks 48, 96, 144, 192 ]
      Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment.
    • Percentage of Participants With No Evidence of Protocol Defined Disease Activity [ Time Frame: Weeks 96, 144, 192 ]
      Protocol-defined disease activity is defined as having at least one of the following: (1). protocol defined relapse (occurrence of new or worsening neurological symptoms attributable to Multiple Sclerosis [MS], as determined using EDSS/Functional Systems Score [FSS] assessment). (2). CDP, as determined using EDSS. (3). a T1 Gd-enhanced lesion after Week 8. (4). a new and/or enlarging T2 hyperintense lesion on magnetic resonance imaging (MRI) after Week 8 compared to the Week 8 MRI scan.
    • Percentage of Participants With no Evidence of Progression (NEP) [ Time Frame: Weeks 96, 192 ]
      NEP is defined as no progression sustained for at least 24 weeks on all of the following three components (CDP; 20 percent [%] increase from baseline in timed 25 Foot Walk Test [T25FWT]; 20% increase from baseline in timed 9 hole peg test [9HPT]). CDP will be assessed using EDSS.
    • Percentage of Participants With no Evidence of Progression Sustained for At Least 24 Weeks and no Active Disease (NEPAD) [ Time Frame: Weeks 96, 192 ]
      NEPAD is defined as no progression on all of the three components of NEP (CDP, T25FWT, 9HPT), no new relapse and no enlarging or new T2 or T1 Gdenhancing lesion. CDP will be assessed using EDSS. Relapse is defined as occurrence of new or worsening neurological symptoms attributable to MS, as determined using EDSS/FSS assessment.
    • Change from Baseline in Multiple Sclerosis Functional Composite (MSFC) Total Score [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192 ]
    • Change from Baseline in MSFC Composite (T25FW) Score [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192 ]
    • Change from Baseline in MSFC Composite (9HPT) Score [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192 ]
    • Change from Baseline in MSFC Composite (Paced Auditory Serial Addition Test [PASAT]) Score [ Time Frame: Baseline, Weeks 24, 48, 72, 96, 120, 144, 168, 192 ]
    • Total Number of T1 Gd-Enhancing Lesions as Detected by Brain MRI [ Time Frame: Baseline, Weeks 8, 24, 48, 96, 144, 192 ]
    • Total Number of New and/or Enlarging T2 Lesion as Detected by Brain MRI [ Time Frame: Baseline, Weeks 8, 24, 48, 96, 144, 192 ]
    • Change From Baseline in T1 Volume as Detected by Brain MRI [ Time Frame: Baseline, Weeks 8, 24, 48, 96, 144, 192 ]
    • Total Number of Fluid-Attenuated Inversion-Recovery (FLAIR) Lesion as Detected by Brain MRI [ Time Frame: Baseline, Weeks 8, 24, 48, 96, 144, 192 ]
    • Change From Baseline in Brain Volume as Detected by Brain MRI [ Time Frame: Baseline, Weeks 8, 24, 48, 96, 144, 192 ]
    • Time to Treatment Discontinuation [ Time Frame: Baseline up to 4 years ]
    • Employment Status: Work Productivity and Activity Impairment Questionnaire (WAPI) Score [ Time Frame: Baseline, Weeks 24, 48, 96, 120, 144, 192 ]
    • SymptoMScreen Composite Score [ Time Frame: Baseline, Weeks 24, 48, 96, 120, 144, 192 ]
    • Quality of Life: Multiple Sclerosis Impact Scale (MSIS)-29 Questionnaire Score [ Time Frame: Baseline, Weeks 24, 48, 96, 120, 144, 192 ]
    • Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 4 years ]
      Short term safety related to the infusion (infusion-related reactions [IRRs], during infusion and up to 24h after) the overall safety is measured continously at clinical visits and including every 8 week telephone visits up to 48 weeks post study.


    Information By: Hoffmann-La Roche

    Dates:
    Date Received: March 16, 2017
    Date Started: March 27, 2017
    Date Completion: January 19, 2022
    Last Updated: May 8, 2017
    Last Verified: May 2017