Multiple Sclerosis, Relapsing-Remitting
Conditions
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.
Interventions
BIOLOGICALOcrelizumab
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.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| Annualized Protocol-defined Relapse Rate at Week 96 | Week 96 | — |
| Time to Onset of 24-week Confirmed Disability Progression | Baseline up to 96 Weeks | — |
| 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 |
| Time to Onset of First New and/or Enlarging T2 Lesion | Baseline up to 96 Weeks | — |
| 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 |
| Change From Baseline to Week 96 in Total T2 Lesion Volume Detected by Brain MRI From | Baseline, Week 96 | — |
| Percentage Change From Baseline to Week 96 in Total T2 Lesion Volume Detected by Brain MRI | Baseline, Week 96 | — |
| 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 |
| 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 at Week 48 and 96 in T1 Hypointense Lesion Volume | Weeks 48, 96 | — |
| Percentage Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume | Weeks 48, 96 | — |
| Adjusted Mean Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume | Weeks 48, 96 | — |
| Adjusted Mean Percentage Change From Baseline in Brain Volume | Weeks 24, 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 | — |
| 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. |
| 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. |
| 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. |
| 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 | — |
| 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. |
Countries
Australia, Belgium, Czechia, Denmark, Estonia, Finland, France, Germany, Ireland, Italy, Netherlands, Norway, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom
Participant flow
Recruitment details
One additional participant was initially enrolled in error and the information provided is based on the ITT population.
Participants by arm
| Arm | Count |
|---|---|
| Ocrelizumab Participants received Ocrelizumab 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. | 680 |
| Total | 680 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Primary Analysis | Adverse Event | 7 |
| Primary Analysis | Commercial ocrelizumab | 3 |
| Primary Analysis | Death | 1 |
| Primary Analysis | Lack of Efficacy | 3 |
| Primary Analysis | Physician Decision | 2 |
| Primary Analysis | Pregnancy | 4 |
| Primary Analysis | Protocol Violation | 2 |
| Primary Analysis | Study Terminated By Sponsor | 3 |
| Primary Analysis | Withdrawal by Subject | 14 |
| Safety Follow-up | Adverse Event | 1 |
| Safety Follow-up | Commercial ocrelizumab | 36 |
| Safety Follow-up | Physician Decision | 1 |
| Safety Follow-up | Pregnancy | 1 |
| Safety Follow-up | Roll-over to a long term extension study | 1 |
| Safety Follow-up | Study terminated by sponsor | 1 |
| Safety Follow-up | Withdrawal by Subject | 9 |
Baseline characteristics
| Characteristic | Ocrelizumab |
|---|---|
| Age, Continuous | 34.2 Years STANDARD_DEVIATION 8.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 579 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 74 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 49 Participants |
| Race (NIH/OMB) White | 625 Participants |
| Sex: Female, Male Female | 436 Participants |
| Sex: Female, Male Male | 244 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 680 | 0 / 64 |
| other Total, other adverse events | 531 / 680 | 14 / 64 |
| serious Total, serious adverse events | 49 / 680 | 6 / 64 |
Outcome results
Primary
Percentage of Participants With No Evidence of Disease Activity (NEDA) as Per Protocol Defined Events During a 96-Week Period
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 frame: Week 96
Population: The modified intent-to-treat (mITT) population was defined as all participants from the ITT population excluding participants with both screening and the baseline EDSS scores missing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ocrelizumab | Percentage of Participants With No Evidence of Disease Activity (NEDA) as Per Protocol Defined Events During a 96-Week Period | 74.8 Percentage of Participants |
Secondary
Absolute Change From Baseline in EDSS Category at 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 frame: Up to Week 96
Population: The modified intent-to-treat (mITT) population was defined as all participants from the ITT population excluding participants with both screening and the baseline EDSS scores missing.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab | Absolute Change From Baseline in EDSS Category at Week 96 | Worsened (>0.5) | 13.4 Percentage of Participants |
| Ocrelizumab | Absolute Change From Baseline in EDSS Category at Week 96 | Stable (Change <= 0.5 and >= -0.5) | 72.2 Percentage of Participants |
| Ocrelizumab | Absolute Change From Baseline in EDSS Category at Week 96 | Improved (<-0.5) | 14.4 Percentage of Participants |
Secondary
Adjusted Mean Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume
Time frame: Weeks 48, 96
Population: All enrolled participants who received any dose of ocrelizumab were included in the ITT population. Participants who prematurely withdrew from the study for any reason and who did not perform any assessment for any reason were also included in the ITT population. Here number of analyzed participants represents participants with data available at given timepoint.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Ocrelizumab | Adjusted Mean Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume | Week 48 | -461.8 mL |
| Ocrelizumab | Adjusted Mean Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume | Week 96 | -576.5 mL |
Secondary
Adjusted Mean Percentage Change From Baseline in Brain Volume
Time frame: Weeks 24, 48, 96
Population: All enrolled participants who received any dose of ocrelizumab were included in the ITT population. Participants who prematurely withdrew from the study for any reason and who did not perform any assessment for any reason were also included in the ITT population. Here number of analyzed participants represents participants with data available at given timepoint.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Ocrelizumab | Adjusted Mean Percentage Change From Baseline in Brain Volume | Week 24 | -0.153 Mean percentage change from baseline |
| Ocrelizumab | Adjusted Mean Percentage Change From Baseline in Brain Volume | Week 48 | -0.445 Mean percentage change from baseline |
| Ocrelizumab | Adjusted Mean Percentage Change From Baseline in Brain Volume | Week 96 | -0.805 Mean percentage change from baseline |
Secondary
Adjusted Mean Percentage Change From Baseline in Cortical Grey Matter Volume
Time frame: Weeks 48, 96
Population: All enrolled participants who received any dose of ocrelizumab were included in the ITT population. Participants who prematurely withdrew from the study for any reason and who did not perform any assessment for any reason were also included in the ITT population. Here number of analyzed participants represents participants with data available at given timepoint.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Ocrelizumab | Adjusted Mean Percentage Change From Baseline in Cortical Grey Matter Volume | Week 48 | -0.312 Mean percentage change from baseline |
| Ocrelizumab | Adjusted Mean Percentage Change From Baseline in Cortical Grey Matter Volume | Week 96 | -0.618 Mean percentage change from baseline |
Secondary
Adjusted Mean Percentage Change From Baseline in White Matter Volume
Time frame: Weeks 48, 96
Population: All enrolled participants who received any dose of ocrelizumab were included in the ITT population. Participants who prematurely withdrew from the study for any reason and who did not perform any assessment for any reason were also included in the ITT population. Here number of analyzed participants represents participants with data available at given timepoint.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Ocrelizumab | Adjusted Mean Percentage Change From Baseline in White Matter Volume | Week 48 | -0.382 Mean percentage change from baseline |
| Ocrelizumab | Adjusted Mean Percentage Change From Baseline in White Matter Volume | Week 96 | -0.745 Mean percentage change from baseline |
Secondary
Annualized Protocol-defined Relapse Rate at Week 96
Time frame: Week 96
Population: All enrolled participants who received any dose of ocrelizumab were included in the ITT population. Participants who prematurely withdrew from the study for any reason and who did not perform any assessment for any reason were also included in the ITT population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ocrelizumab | Annualized Protocol-defined Relapse Rate at Week 96 | 0.030 Relapses per participant per year |
Secondary
Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume
Time frame: Weeks 48, 96
Population: All enrolled participants who received any dose of ocrelizumab were included in the ITT population. Participants who prematurely withdrew from the study for any reason and who did not perform any assessment for any reason were also included in the ITT population. Here number of analyzed participants represents participants with data available at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ocrelizumab | Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume | Week 48 | -416.5 mL | Standard Deviation 1224.3 |
| Ocrelizumab | Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume | Week 96 | -528.5 mL | Standard Deviation 1144.7 |
Secondary
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
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.
Time frame: Baseline, Weeks 48, 96
Population: All enrolled participants who received any dose of ocrelizumab were included in the ITT population. Participants who prematurely withdrew from the study for any reason and who did not perform any assessment for any reason were also included in the ITT population. Here number of analyzed participants represents participants with data available at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ocrelizumab | 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 | Week 96 | -1.5 Points on scale | Standard Deviation 5.4 |
| Ocrelizumab | 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 | 25.0 Points on scale | Standard Deviation 6.3 |
| Ocrelizumab | 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 | Week 48 | -1.9 Points on scale | Standard Deviation 5.3 |
Secondary
Change From Baseline to Week 96 in Expanded Disability Status Scale (EDSS)
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 frame: Baseline, Weeks: 24, 48, 72, 96
Population: The modified intent-to-treat (mITT) population was defined as all participants from the ITT population excluding participants with both screening and the baseline EDSS scores missing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ocrelizumab | Change From Baseline to Week 96 in Expanded Disability Status Scale (EDSS) | Week 72 | -0.03 Points on scale | Standard Deviation 0.85 |
| Ocrelizumab | Change From Baseline to Week 96 in Expanded Disability Status Scale (EDSS) | Week 96 | -0.01 Points on scale | Standard Deviation 0.85 |
| Ocrelizumab | Change From Baseline to Week 96 in Expanded Disability Status Scale (EDSS) | Baseline | 2.09 Points on scale | Standard Deviation 1.06 |
| Ocrelizumab | Change From Baseline to Week 96 in Expanded Disability Status Scale (EDSS) | Week 24 | -0.02 Points on scale | Standard Deviation 0.64 |
| Ocrelizumab | Change From Baseline to Week 96 in Expanded Disability Status Scale (EDSS) | Week 48 | 0.01 Points on scale | Standard Deviation 0.82 |
Secondary
Change From Baseline to Week 96 in Total T2 Lesion Volume Detected by Brain MRI From
Time frame: Baseline, Week 96
Population: All enrolled participants who received any dose of ocrelizumab were included in the ITT population. Participants who prematurely withdrew from the study for any reason and who did not perform any assessment for any reason were also included in the ITT population. Here number of analyzed participants represents participants with data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ocrelizumab | Change From Baseline to Week 96 in Total T2 Lesion Volume Detected by Brain MRI From | -558.6 mL | Standard Deviation 1194.6 |
Secondary
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
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.
Time frame: Baseline, Weeks: 48, 96
Population: All enrolled participants who received any dose of ocrelizumab were included in the ITT population. Participants who prematurely withdrew from the study for any reason and who did not perform any assessment for any reason were also included in the ITT population. Here number of analyzed participants represents participants with data available at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ocrelizumab | 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 | 53.8 Correct responses over 90 seconds | Standard Deviation 13 |
| Ocrelizumab | 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 | Week 48 | 2.5 Correct responses over 90 seconds | Standard Deviation 9.8 |
| Ocrelizumab | 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 | Week 96 | 1.3 Correct responses over 90 seconds | Standard Deviation 10.2 |
Secondary
Mean Number of New and/or Enlarging T2 Hyperintense Lesions Per MRI Scan
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
Time frame: Weeks 24, 48, 96
Population: All enrolled participants who received any dose of ocrelizumab were included in the ITT population. Participants who prematurely withdrew from the study for any reason and who did not perform any assessment for any reason were also included in the ITT population. Here number of analyzed participants represents participants with data available at given timepoint.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Ocrelizumab | Mean Number of New and/or Enlarging T2 Hyperintense Lesions Per MRI Scan | Week 24 | 0.053 Lesions per scan |
| Ocrelizumab | Mean Number of New and/or Enlarging T2 Hyperintense Lesions Per MRI Scan | Week 48 | 0.009 Lesions per scan |
| Ocrelizumab | Mean Number of New and/or Enlarging T2 Hyperintense Lesions Per MRI Scan | Week 96 | 0.011 Lesions per scan |
Secondary
Mean Number of T1 Gd-enhancing Lesions Per MRI Scan at Weeks 24, 48 and 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
Time frame: Weeks: 24, 48, 96
Population: All enrolled participants who received any dose of ocrelizumab were included in the ITT population. Participants who prematurely withdrew from the study for any reason and who did not perform any assessment for any reason were also included in the ITT population. Here number of analyzed participants represents participants with data available at given timepoint.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Ocrelizumab | Mean Number of T1 Gd-enhancing Lesions Per MRI Scan at Weeks 24, 48 and 96 | Week 24 | 0.004 Lesions per scan |
| Ocrelizumab | Mean Number of T1 Gd-enhancing Lesions Per MRI Scan at Weeks 24, 48 and 96 | Week 48 | 0.004 Lesions per scan |
| Ocrelizumab | Mean Number of T1 Gd-enhancing Lesions Per MRI Scan at Weeks 24, 48 and 96 | Week 96 | NA Lesions per scan |
Secondary
Percentage Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume
Time frame: Weeks 48, 96
Population: All enrolled participants who received any dose of ocrelizumab were included in the ITT population. Participants who prematurely withdrew from the study for any reason and who did not perform any assessment for any reason were also included in the ITT population. Here number of analyzed participants represents participants with data available at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ocrelizumab | Percentage Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume | Week 48 | -4.0 Percentage change from baseline | Standard Deviation 149.7 |
| Ocrelizumab | Percentage Change From Baseline at Week 48 and 96 in T1 Hypointense Lesion Volume | Week 96 | -12.5 Percentage change from baseline | Standard Deviation 21.1 |
Secondary
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
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.
Time frame: Baseline, Weeks 48, 96
Population: All enrolled participants who received any dose of ocrelizumab were included in the ITT population. Participants who prematurely withdrew from the study for any reason and who did not perform any assessment for any reason were also included in the ITT population. Here number of analyzed participants represents participants with data available at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ocrelizumab | 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 | Week 96 | 4.8 Percentage change from baseline | Standard Deviation 30.6 |
| Ocrelizumab | 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 | Week 48 | 7.2 Percentage change from baseline | Standard Deviation 30.8 |
Secondary
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
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.
Time frame: Baseline, Weeks: 48, 96
Population: All enrolled participants who received any dose of ocrelizumab were included in the ITT population. Participants who prematurely withdrew from the study for any reason and who did not perform any assessment for any reason were also included in the ITT population. Here number of analyzed participants represents participants with data available at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ocrelizumab | 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 | Week 48 | -4.4 Percentage change from baseline | Standard Deviation 31.1 |
| Ocrelizumab | 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 | Week 96 | -2.0 Percentage change from baseline | Standard Deviation 33.7 |
Secondary
Percentage Change From Baseline to Week 96 in Total T2 Lesion Volume Detected by Brain MRI
Time frame: Baseline, Week 96
Population: All enrolled participants who received any dose of ocrelizumab were included in the ITT population. Participants who prematurely withdrew from the study for any reason and who did not perform any assessment for any reason were also included in the ITT population. Here number of analyzed participants represents participants with data available.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ocrelizumab | Percentage Change From Baseline to Week 96 in Total T2 Lesion Volume Detected by Brain MRI | -8.5 Percentage Change From Baseline | Standard Deviation 18.2 |
Secondary
Percentage of Participants Free From a Protocol-Defined Event of Disease Activity During 24 Weeks Period
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 frame: Baseline up to 24 weeks
Population: The modified intent-to-treat (mITT) population was defined as all participants from the ITT population excluding participants with both screening and the baseline EDSS scores missing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ocrelizumab | Percentage of Participants Free From a Protocol-Defined Event of Disease Activity During 24 Weeks Period | 87.1 Percentage of Participants |
Secondary
Percentage of Participants Free From a Protocol-Defined Event of Disease Activity During 48 Weeks Period
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 frame: Baseline up to 48 weeks
Population: The modified intent-to-treat (mITT) population was defined as all participants from the ITT population excluding participants with both screening and the baseline EDSS scores missing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ocrelizumab | Percentage of Participants Free From a Protocol-Defined Event of Disease Activity During 48 Weeks Period | 82.6 Percentage of Participants |
Secondary
Percentage of Participants With a Baseline EDSS Score ≥2 With CDI at 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 frame: Week 96
Population: The modified intent-to-treat (mITT) population was defined as all participants from the ITT population excluding participants with both screening and the baseline EDSS scores missing.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ocrelizumab | Percentage of Participants With a Baseline EDSS Score ≥2 With CDI at Week 96 | 17.3 Percentage of Participants |
Secondary
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
Population: Safety analyses were done on the ITT population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ocrelizumab | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Malignancies | 0.4 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs leading to study drug discontinuation | 0.7 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Pregnancies | 0.7 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Infusion-related reactions (IRRs) | 43.2 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 89.1 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs leading to study drug discontinuation | 1.0 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE | 7.2 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious IRRs | 0.1 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Deaths | 0.1 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious infections | 1.6 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Infections | 66.9 Percentage of Participants |
| Ocrelizumab | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs leading to dose modification/interruptionb | 15.0 Percentage of Participants |
| Ocrelizumab Safety Follow-up | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Infections | 28.1 Percentage of Participants |
| Ocrelizumab Safety Follow-up | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs leading to study drug discontinuation | NA Percentage of Participants |
| Ocrelizumab Safety Follow-up | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAEs leading to study drug discontinuation | NA Percentage of Participants |
| Ocrelizumab Safety Follow-up | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AEs leading to dose modification/interruptionb | NA Percentage of Participants |
| Ocrelizumab Safety Follow-up | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Infusion-related reactions (IRRs) | 0 Percentage of Participants |
| Ocrelizumab Safety Follow-up | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious infections | 0 Percentage of Participants |
| Ocrelizumab Safety Follow-up | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Malignancies | 0 Percentage of Participants |
| Ocrelizumab Safety Follow-up | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Pregnancies | 1.5 Percentage of Participants |
| Ocrelizumab Safety Follow-up | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 57.8 Percentage of Participants |
| Ocrelizumab Safety Follow-up | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | SAE | 9.4 Percentage of Participants |
| Ocrelizumab Safety Follow-up | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Serious IRRs | 0 Percentage of Participants |
| Ocrelizumab Safety Follow-up | Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Deaths | 0 Percentage of Participants |
Secondary
Time to First Protocol-Defined Event of Disease Activity
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.
Time frame: Baseline up to 96 Weeks
Population: The modified intent-to-treat (mITT) population was defined as all participants from the ITT population excluding participants with both screening and the baseline EDSS scores missing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ocrelizumab | Time to First Protocol-Defined Event of Disease Activity | NA Weeks |
Secondary
Time to Onset of 24-week Confirmed Disability Progression
Time frame: Baseline up to 96 Weeks
Population: The modified intent-to-treat (mITT) population was defined as all participants from the ITT population excluding participants with both screening and the baseline EDSS scores missing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ocrelizumab | Time to Onset of 24-week Confirmed Disability Progression | NA Weeks |
Secondary
Time to Onset of First New and/or Enlarging T2 Lesion
Time frame: Baseline up to 96 Weeks
Population: All enrolled participants who received any dose of ocrelizumab were included in the ITT population. Participants who prematurely withdrew from the study for any reason and who did not perform any assessment for any reason were also included in the ITT population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ocrelizumab | Time to Onset of First New and/or Enlarging T2 Lesion | NA Weeks |
Secondary
Time to Onset of First Protocol-Defined Relapse
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 frame: Baseline up to 96 Weeks
Population: The modified intent-to-treat (mITT) population was defined as all participants from the ITT population excluding participants with both screening and the baseline EDSS scores missing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ocrelizumab | Time to Onset of First Protocol-Defined Relapse | NA Weeks |
Secondary
Volume of New and/or Enlarging T2 Hyperintense Lesions Volume of Lesions Per MRI Scan at 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.
Time frame: Weeks 24, 48, 96
Population: All enrolled participants who received any dose of ocrelizumab were included in the ITT population. Participants who prematurely withdrew from the study for any reason and who did not perform any assessment for any reason were also included in the ITT population. Here number of analyzed participants represents participants with data available at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ocrelizumab | Volume of New and/or Enlarging T2 Hyperintense Lesions Volume of Lesions Per MRI Scan at Weeks 24, 48, 96 | Week 24 | 21.4 uL | Standard Deviation 241.7 |
| Ocrelizumab | Volume of New and/or Enlarging T2 Hyperintense Lesions Volume of Lesions Per MRI Scan at Weeks 24, 48, 96 | Week 48 | 23.1 uL | Standard Deviation 510.2 |
| Ocrelizumab | Volume of New and/or Enlarging T2 Hyperintense Lesions Volume of Lesions Per MRI Scan at Weeks 24, 48, 96 | Week 96 | 3.7 uL | Standard Deviation 41.6 |