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

Hoffmann-La Roche163 sites in 8 countries681 target enrollmentSeptember 9, 2016

ConditionsMultiple Sclerosis, Relapsing-Remitting

Overview

Phase: Phase 3
Intervention: Not specified
Conditions: Multiple Sclerosis, Relapsing-Remitting
Sponsor: Hoffmann-La Roche
Enrollment: 681
Locations: 163
Primary Endpoint: Percentage of Participants With No Evidence of Disease Activity (NEDA) as Per Protocol Defined Events During a 96-Week Period
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

September 9, 2016

End Date

December 15, 2020

Last Updated

4 years ago

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Hoffmann-La Roche

Responsible Party

Sponsor

Eligibility Criteria

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

Outcomes

Primary Outcomes

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

Secondary Outcomes

Percentage Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume(Weeks 48, 96)
Absolute Change From Baseline in EDSS Category at Week 96(Up to Week 96)
Change From Baseline to Week 96 in Total T2 Lesion Volume Detected by Brain MRI From(Baseline, Week 96)
Adjusted Mean Percentage Change From Baseline in Brain Volume(Weeks 24, 48, 96)
Mean Number of T1 Gd-enhancing Lesions Per MRI Scan at Weeks 24, 48 and 96(Weeks: 24, 48, 96)
Percentage of Participants With a Baseline EDSS Score ≥2 With CDI at Week 96(Week 96)
Time to Onset of First New and/or Enlarging T2 Lesion(Baseline up to 96 Weeks)
Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume(Weeks 48, 96)
Adjusted Mean Percentage Change From Baseline in Cortical Grey Matter Volume(Weeks 48, 96)
Adjusted Mean Percentage Change From Baseline in White Matter Volume(Weeks 48, 96)
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(Baseline, Weeks 48, 96)
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(Baseline, Weeks: 48, 96)
Change From Baseline to Week 96 in Expanded Disability Status Scale (EDSS)(Baseline, Weeks: 24, 48, 72, 96)
Time to Onset of First Protocol-Defined Relapse(Baseline up to 96 Weeks)
Volume of New and/or Enlarging T2 Hyperintense Lesions Volume of Lesions Per MRI Scan at Weeks 24, 48, 96(Weeks 24, 48, 96)
Adjusted Mean Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume(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(Baseline, Weeks: 48, 96)
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Baseline up to to 96 weeks after the end of the Treatment Period)
Percentage of Participants Free From a Protocol-Defined Event of Disease Activity During 24 Weeks Period(Baseline up to 24 weeks)
Percentage of Participants Free From a Protocol-Defined Event of Disease Activity During 48 Weeks Period(Baseline up to 48 weeks)
Time to First Protocol-Defined Event of Disease Activity(Baseline up to 96 Weeks)
Annualized Protocol-defined Relapse Rate at Week 96(Week 96)
Time to Onset of 24-week Confirmed Disability Progression(Baseline up to 96 Weeks)
Percentage Change From Baseline to Week 96 in Total T2 Lesion Volume Detected by Brain MRI(Baseline, Week 96)
Mean Number of New and/or Enlarging T2 Hyperintense Lesions Per MRI Scan(Weeks 24, 48, 96)
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(Baseline, Weeks 48, 96)