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)

Phase 3

Completed

Conditions: Multiple Sclerosis, Relapsing-Remitting

Registration Number: NCT02861014

Lead Sponsor: Hoffmann-La Roche

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 available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 681

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With No Evidence of Disease Activity (NEDA) as Per Protocol Defined Events During a 96-Week Period	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 Outcome Measures

Name	Time	Method
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	The EDSS is an ordinal clinical rating scale ranging from 0 (normal neurologic examination) to 10 (death due to MS) in half-point increments.
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	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
Percentage of Participants With a Baseline EDSS Score ≥2 With CDI at Week 96	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.
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	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	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.
Change From Baseline to Week 96 in Expanded Disability Status Scale (EDSS)	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.
Time to Onset of First Protocol-Defined Relapse	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
Volume of New and/or Enlarging T2 Hyperintense Lesions Volume of Lesions Per MRI Scan at Weeks 24, 48, 96	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.
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	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.
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	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	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	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.
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	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 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	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.

Trial Locations

Locations (163): St George Hospital
🇦🇺
Kogarah, New South Wales, New South Wales, Australia
Hospital Erasme
🇧🇪
Bruxelles, Belgium
Cliniques Universitaires St-Luc
🇧🇪
Bruxelles, Belgium
UZ Antwerpen
🇧🇪
Edegem, Belgium
UZ Gent
🇧🇪
Gent, Belgium
CHU Tivoli
🇧🇪
La Louvière, Belgium
UZ Leuven Gasthuisberg
🇧🇪
Leuven, Belgium
Nationaal MS Centrum
🇧🇪
Melsbroek, Belgium
Revalidatie en MS Centrum
🇧🇪
Overpelt, Belgium
Fakultni nemocnice u sv. Anny; Neurologicka klinika
🇨🇿
Brno, Czechia
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St George Hospital
🇦🇺Kogarah, New South Wales, New South Wales, Australia