A Single Arm, Open Label Multicentre Extension Study To Evaluate The Effectiveness And Safety Of Ocrelizumab In Patients With Multiple Sclerosis Previously Enrolled In A F. Hoffmann-La Roche Sponsored Ocrelizumab Phase IIIb/IV Clinical Trials
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,055
- 试验地点
- 317
- 主要终点
- Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 Weeks From CASTING Baseline to LIBERTO Week 96
研究概览
简要总结
This extension study will evaluate the effectiveness and safety of ocrelizumab in multiple sclerosis (MS) participants who were previously enrolled in a F. Hoffmann-La Roche (Roche) sponsored ocrelizumab phase IIIb/IV trial (i.e. the Parent, P-trial).
详细描述
This is a single arm, open label, multicenter extension study in participants who completed treatment period with ocrelizumab in the Roche P-trials. Participants will receive treatment with ocrelizumab as single 600 mg infusions every 24 weeks for two years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed Informed Consent Form
- •Able to comply with the study protocol, in the investigator's judgment
- •Completed the treatment period of Roche sponsored ocrelizumab P-trials
排除标准
- •Hypersensitivity to ocrelizumab or to any of its excipients.
- •Participantss in a severely immunocompromised state until the condition resolves.
- •Evidence of any adverse event potentially attributable to ocrelizumab, for which the local label recommends permanent discontinuation.
- •Existence of a contra-indication as per SmPC
- •Prohibited concomitant medication as specified in protocol
- •Participants intending to become pregnant during the study or within 6 months after the last dose of the study drug in the parent study
研究组 & 干预措施
Ocrelizumab
Participants will receive a single 600-mg infusion of Ocrelizumab every 24 weeks up to Week 72 of this study.
干预措施: Ocrelizumab (Drug)
结局指标
主要结局
Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 Weeks From CASTING Baseline to LIBERTO Week 96
时间窗: From CASTING Baseline to LIBERTO Week 96 (up to 4 years)
Disability progression was defined as an increase of ≥ 1.0 point from the baseline Expanded Disability Status Scale (EDSS) score that was not attributable to another etiology (e.g., fever, concurrent illness, or concomitant medication) when the baseline score was 5.5 or less, \& ≥ 0.5 when the baseline score was above 5.5. For participants with an EDSS of 0, progression is defined as a change ≥1.5 points. Disability progression was considered confirmed when increase in EDSS was confirmed at a regularly scheduled visit at least 24 weeks after initial documentation of neurological worsening. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated \& scored as Functional Systems Score (FSSs). Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Median was analysed using Kaplan-Meier(K-M) method.
Time to Onset of CDP Sustained for at Least 24 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
时间窗: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Disability progression was defined as an increase of ≥ 1.0 point from the baseline EDSS score that was not attributable to another etiology (e.g., fever, concurrent illness, or concomitant medication) when the baseline score was 5.5 or less, \& ≥ 0.5 when the baseline score was above 5.5. For participants with an EDSS of 0, progression is defined as a change ≥1.5 points. Disability progression was considered confirmed when increase in EDSS was confirmed at a regularly scheduled visit at least 24 weeks after initial documentation of neurological worsening. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated \& scored as FSSs. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Median was analysed using K-M method.
Time to Onset of CDP Sustained for at Least 48 Weeks From CASTING Baseline to LIBERTO Week 96
时间窗: From CASTING Baseline to LIBERTO Week 96 (up to 4 years)
Disability progression was defined as an increase of ≥ 1.0 point from the baseline EDSS score that was not attributable to another etiology (e.g., fever, concurrent illness, or concomitant medication) when the baseline score was 5.5 or less, \& ≥ 0.5 when the baseline score was above 5.5. For participants with an EDSS of 0, progression is defined as a change ≥1.5 points. Disability progression was considered confirmed when increase in EDSS was confirmed at two scheduled visit at least 48 weeks after initial documentation of neurological worsening. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated \& scored as FSSs. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Median was analysed using K-M method.
Time to Onset of CDP Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
时间窗: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Disability progression was defined as an increase of ≥ 1.0 point from the baseline EDSS score that was not attributable to another etiology (e.g., fever, concurrent illness, or concomitant medication) when the baseline score was 5.5 or less, \& ≥ 0.5 when the baseline score was above 5.5. For participants with an EDSS of 0, progression is defined as a change ≥1.5 points. isability progression was considered confirmed when increase in EDSS was confirmed at two scheduled visit at least 48 weeks after initial documentation of neurological worsening. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated \& scored as FSSs. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Median was analysed using K-M method.
Percentage of Participants Who Had CDP Sustained for at Least 24 Weeks From CASTING Baseline to LIBERTO Week 96
时间窗: From CASTING Baseline to LIBERTO Week 96 (up to 4 years)
Disability progression was defined as an increase of ≥ 1.0 point from the baseline EDSS score that was not attributable to another etiology (e.g., fever, concurrent illness, or concomitant medication) when the baseline score was 5.5 or less, \& ≥ 0.5 when the baseline score was above 5.5. For participants with an EDSS of 0, progression is defined as a change ≥1.5 points. Disability progression was considered confirmed when increase in EDSS was confirmed at a regularly scheduled visit at least 24 weeks after initial documentation of neurological worsening. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated \& scored as FSSs. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Percentages are rounded off.
Percentage of Participants Who Had CDP Sustained for at Least 24 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
时间窗: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Disability progression was defined as an increase of ≥ 1.0 point from the baseline EDSS score that was not attributable to another etiology (e.g., fever, concurrent illness, or concomitant medication) when the baseline score was 5.5 or less, \& ≥ 0.5 when the baseline score was above 5.5. For participants with an EDSS of 0, progression is defined as a change ≥1.5 points. Disability progression was considered confirmed when increase in EDSS was confirmed at a regularly scheduled visit at least 24 weeks after initial documentation of neurological worsening. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated \& scored as FSSs. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Percentages are rounded off.
Percentage of Participants Who Had CDP Sustained for at Least 48 Weeks From CASTING Baseline to LIBERTO Week 96
时间窗: From CASTING Baseline to LIBERTO Week 96 (up to 4 years)
Disability progression was defined as an increase of ≥ 1.0 point from the baseline EDSS score that was not attributable to another etiology (e.g., fever, concurrent illness, or concomitant medication) when the baseline score was 5.5 or less, \& ≥ 0.5 when the baseline score was above 5.5. For participants with an EDSS of 0, progression is defined as a change ≥1.5 points. isability progression was considered confirmed when increase in EDSS was confirmed at two scheduled visit at least 48 weeks after initial documentation of neurological worsening. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated \& scored as FSSs. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Percentages are rounded off.
Percentage of Participants Who Had CDP Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
时间窗: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Disability progression was defined as an increase of ≥ 1.0 point from the baseline EDSS score that was not attributable to another etiology (e.g., fever, concurrent illness, or concomitant medication) when the baseline score was 5.5 or less, \& ≥ 0.5 when the baseline score was above 5.5. For participants with an EDSS of 0, progression is defined as a change ≥1.5 points. isability progression was considered confirmed when increase in EDSS was confirmed at two scheduled visit at least 48 weeks after initial documentation of neurological worsening. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated \& scored as FSSs. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Percentages are rounded off.
Percentage of Participants Who Had Confirmed Disability Improvement (CDI) Sustained for at Least 24 Weeks From CASTING Baseline to LIBERTO Week 96
时间窗: From CASTING Baseline to LIBERTO Week 96 (up to 4 years)
CDI was defined as an improvement of ≥1 point on the EDSS score confirmed at a regular scheduled visit at least 24 weeks after the initial documentation of neurological status when the baseline score is 5.5 or less, and ≥ 0.5 when the baseline score is above 5.5. The CDI was measured only participants with a baseline EDSS of ≥2.0. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated \&scored as FSS. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Percentages are rounded off.
Percentage of Participants Who Had CDI Sustained for at Least 24 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
时间窗: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
CDI was defined as an improvement of ≥1 point on the EDSS score confirmed at a regular scheduled visit at least 24 weeks after the initial documentation of neurological status when the baseline score is 5.5 or less, and ≥ 0.5 when the baseline score is above 5.5. The CDI was measured only participants with a baseline EDSS of ≥2.0. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated \&scored as FSS. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Percentages are rounded off.
Percentage of Participants Who Had CDI Sustained for at Least 48 Weeks From CASTING Baseline to LIBERTO Week 96
时间窗: From CASTING Baseline to LIBERTO Week 96 (up to 4 years)
CDI was defined as an improvement of ≥1 point on the EDSS score confirmed at two scheduled visits at least 48 weeks after the initial documentation of neurological status when the baseline score is 5.5 or less, and ≥ 0.5 when the baseline score is above 5.5. The CDI was measured only participants with a baseline EDSS of ≥2.0. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated \& scored as FSS. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Percentages are rounded off.
Percentage of Participants Who Had CDI Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
时间窗: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
CDI was defined as an improvement of ≥1 point on the EDSS score confirmed at two scheduled visits at least 48 weeks after the initial documentation of neurological status when the baseline score is 5.5 or less, and ≥ 0.5 when the baseline score is above 5.5. The CDI was measured only participants with a baseline EDSS of ≥2.0. The EDSS is based on a standard neurological examination, incorporating 7 functional systems that were rated \& scored as FSS. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Percentages are rounded off.
Percentage of Participants Who Had Improved, Stable or Worsened Disability Compared With CASTING Baseline in EDSS Category at LIBERTO Week 96
时间窗: At LIBERTO Week 96
The EDSS is based on a standard neurological examination, incorporating 7 functional systems (pyramidal, cerebellar, brainstem, sensory, bowel \& bladder, visual, \& cerebral) rated \&scored as FSSs. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. These ratings were then used in conjunction with observations \& information concerning ambulation \& use of assistive devices to determine the EDSS score. The EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Participants were considered stable when the change from baseline in score was between -0.5 and +0.5, worsened when the change was \> 0.5, and improved when the change in score was \< -0.5. Percentages are rounded off.
Percentage of Participants Who Had Stable or Worsened Disability Compared With ENSEMBLE Baseline in EDSS Category at LIBERTO Week 96
时间窗: At LIBERTO Week 96
The EDSS is based on a standard neurological examination, incorporating 7 functional systems (pyramidal, cerebellar, brainstem, sensory, bowel \& bladder, visual, \& cerebral) rated \&scored as FSSs. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. These ratings were then used in conjunction with observations \& information concerning ambulation \& use of assistive devices to determine the EDSS score. The EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Participants were considered stable when the change from baseline in score was between -0.5 and +0.5 and worsened when the change was \> 0.5. Percentages are rounded off.
Change From CASTING Baseline in EDSS Score to LIBERTO Week 96
时间窗: CASTING Baseline to LIBERTO Week 96 (up to 4 years)
The EDSS is based on a standard neurological examination, incorporating 7 functional systems (pyramidal, cerebellar, brainstem, sensory, bowel \& bladder, visual, \& cerebral) rated \&scored as Functional Systems Score (FSSs). Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. These ratings were then used in conjunction with observations \& information concerning ambulation \& use of assistive devices to determine the EDSS score. The EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Estimates are from analysis based on mixed-effect model of repeated measures (MMRM).
Change From ENSEMBLE Baseline in EDSS Score to LIBERTO Week 96
时间窗: ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
The EDSS is based on a standard neurological examination, incorporating 7 functional systems (pyramidal, cerebellar, brainstem, sensory, bowel \& bladder, visual, \& cerebral) rated \&scored as FSSs. Each FSS was ordinal clinical rating scale ranging from 0 to 5 or 6. These ratings were then used in conjunction with observations \& information concerning ambulation \& use of assistive devices to determine the EDSS score. The EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death). Estimates are from analysis based on MMRM.
Time to ≥ 20% Increase in 25-foot Walk Test (T25FWT) Sustained for at Least 24 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
时间窗: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Sustained T25FWT was defined as a 24-week T25FWT still has a confirmed 20% increase until the last available visit. T25FWT test is a performance measure used to assess walking speed based on a timed 25-foot walk. The participant was directed to start at one end of a clearly marked 25-foot course and was instructed to walk 25 feet as quickly and safely as possible. The Examining Investigator timed the participants from the start of the walk to the end of the 25 feet. The task was immediately administered again by having the participant walk back the same distance. Participants could use assistive devices (e.g., cane, crutch, or rollator) when performing the task. Score was the average of the two completed trials, measured in seconds. The longer it takes to walk, higher the score, indicating deterioration. Median was analysed using K-M method.
Time to ≥ 20% Increase in 25FWT Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
时间窗: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Sustained T25FWT was defined as a 48-week T25FWT still has a confirmed 20% increase until the last available visit. T25FWT test is a performance measure used to assess walking speed based on a timed 25-foot walk. The participant was directed to start at one end of a clearly marked 25-foot course and was instructed to walk 25 feet as quickly and safely as possible. The Examining Investigator timed the participants from the start of the walk to the end of the 25 feet. The task was immediately administered again by having the participant walk back the same distance. Participants could use assistive devices (e.g., cane, crutch, or rollator) when performing the task. Score was the average of the two completed trials, measured in seconds. The longer it takes to walk, higher the score, indicating deterioration. Median was analysed using K-M method.
Time to ≥ 20% Increase in 9 Hole Peg Test (9HPT) Sustained for at Least 24 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
时间窗: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Sustained 9HPT was defined as a 24-week 9HPT still has a confirmed 20% increase until the last available visit. In 9-HPT, participants had to place \& remove pegs 1 by 1 into 9 holes arranged in a board \& complete 2 successful trials for each hand \& the amount of time (in seconds) required was recorded. The longer it took complete test, higher the scores, indicating deterioration. Median was analysed using K-M method.
Time to ≥ 20% Increase in 9HPT Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
时间窗: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Sustained 9HPT was defined as a 48-week 9HPT still has a confirmed 20% increase until the last available visit. In 9-HPT, participants had to place \& remove pegs 1 by 1 into 9 holes arranged in a board \& complete 2 successful trials for each hand \& the amount of time (in seconds) required was recorded. The longer it took complete test, higher the scores, indicating deterioration. Median was analysed using K-M method.
Percentage of Participants With ≥ 20% Increase in T25FWT Sustained for at Least 24 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
时间窗: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Sustained T25FWT was defined as a 24-week T25FWT still has a confirmed 20% increase until the last available visit. T25FWT test is a performance measure used to assess walking speed based on a timed 25-foot walk. The participant was directed to start at one end of a clearly marked 25-foot course and was instructed to walk 25 feet as quickly and safely as possible. The Examining Investigator timed the participants from the start of the walk to the end of the 25 feet. The task was immediately administered again by having the participant walk back the same distance. Participants could use assistive devices (e.g., cane, crutch, or rollator) when performing the task. Score was the average of the two completed trials, measured in seconds. The longer it takes to walk, higher the score, indicating deterioration. Percentage is rounded off.
Percentage of Participants With ≥ 20% Increase in T25FWT Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
时间窗: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Sustained T25FWT was defined as a 48-week T25FWT still has a confirmed 20% increase until the last available visit. T25FWT test is a performance measure used to assess walking speed based on a timed 25-foot walk. The participant was directed to start at one end of a clearly marked 25-foot course and was instructed to walk 25 feet as quickly and safely as possible. The Examining Investigator timed the participants from the start of the walk to the end of the 25 feet. The task was immediately administered again by having the participant walk back the same distance. Participants could use assistive devices (e.g., cane, crutch, or rollator) when performing the task. Score was the average of the two completed trials, measured in seconds. The longer it takes to walk, higher the score, indicating deterioration. Percentage is rounded off.
Percentage of Participants With ≥ 20% Increase in 9HPT Sustained for at Least 24 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
时间窗: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Sustained 9HPT was defined as a 24-week 9HPT still has a confirmed 20% increase until the last available visit. In 9-HPT, participants had to place \& remove pegs 1 by 1 into 9 holes arranged in a board \& complete 2 successful trials for each hand \& the amount of time (in seconds) required was recorded. The longer it took complete test, higher the scores, indicating deterioration. Percentage is rounded off.
Percentage of Participants With ≥ 20% Increase in 9HPT Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
时间窗: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Sustained 9HPT was defined as a 48-week 9HPT still has a confirmed 20% increase until the last available visit. In 9-HPT, participants had to place \& remove pegs 1 by 1 into 9 holes arranged in a board \& complete 2 successful trials for each hand \& the amount of time (in seconds) required was recorded. The longer it took complete test, higher the scores, indicating deterioration. Percentage is rounded off.
Mean change from inclusion in parent study in EDSS score over the course of the treatment
时间窗: Up to 2 years
Time to onset of CDP sustained for at least 24 weeks and for at least 48 weeks
时间窗: Up to 2 Years
Percentage of participants who have confirmed disability improvement (CDI), CDP for at least 24 weeks and for at least 48 weeks yearly and over the duration of the treatment
时间窗: Up to 2 years
Percentage of participants who have improved, stable or worsened disability compared with baseline
时间窗: Up to 2 years
Improved, stable or worsened disability is measured by expanded disability status scale (EDSS) (annually/by epoch and over duration of the study) Stable EDSS is defined as EDSS change +/- 0.5. Worsening is \> 0.5 increase of EDSS, Improvement is \>0.5 decrease of EDSS
Time to 20% increase in timed 25-foot walk test (T25FWT)
时间窗: Up to 2 years
Time to 20% increase in timed nine-hole peg test (9HPT) sustained for at least 24 weeks and for at least 48 weeks, and proportion of patients achieving a sustained increase assessed yearly and at the end treatment
次要结局
- Time to First Protocol-Defined Event of Disease Activity(From CASTING Baseline to LIBERTO Week 96 (up to 4 years); From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years))
- Time to First Relapse(From CASTING Baseline to LIBERTO Week 96 (up to 4 years); From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years))
- Annualized Protocol-Defined Relapse Rate(From CASTING Baseline to LIBERTO Week 96 (up to 4 years); From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years))
- Percentage of Relapse Free Participants(From CASTING Baseline to LIBERTO Week 96 (up to 4 years); From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years))
- Percentage of Participants With No Protocol-Defined Event of Disease Activity (NEDA) for CASTING Rollover Cohort(From CASTING Baseline to LIBERTO Week 96 (up to 4 years))
- Percentage of Participants With NEDA for ENSEMBLE Cohort(From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years))
- Percentage of Participants With No Evidence of Progression (NEP) From ENSEMBLE Baseline to LIBERTO Week 96(From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years))
- Percentage of Participants With No Evidence of Progression Sustained for at Least 24 Weeks and Disease Activity (NEPAD) From ENSEMBLE Baseline ENSEMBLE to LIBERTO Week 96(From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years))
- Change From Baseline in Symbol Digit Modalities Test (SDMT) Score for CASTING Rollover Cohort(CASTING Baseline to LIBERTO Week 96 (up to 4 years))
- Time to 8-point Improvement Change in the SDMT Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96(From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years))
- Rate of Gadolinium-enhancing Lesions on T1Gd+ Lesions as Detected by Brain MRI(From CASTING Week 24 to LIBERTO Week 96 (up to 184 weeks); From ENSEMBLE Week 24 to LIBERTO Week 96 (up to 264 weeks))
- Rate of New or Enlarging T2 Lesions as Detected by Brain MRI(From CASTING Week 24 to LIBERTO Week 96 (up to 184 weeks); From ENSEMBLE Week 24 to LIBERTO Week 96 (up to 264 weeks))
- Change in Total T1 Hypointense Lesion Volume Detected by Brain MRI(At LIBERTO Week 96)
- Rate of Fluid-Attenuated Inversion Recovery (FLAIR) Late Enhancing Lesions With Leakage as Detected by Brain MRI Over Time(From LIBERTO Week 24 to LIBERTO Week 96; From ENSEMBLE Week 24 to LIBERTO Week 96 (up to 264 weeks))
- Percentage Change in Brain Volume as Detected by Brain MRI Over Time(From Week 8 of CASTING and ENSEMBLE Cohorts up to LIBERTO Week 96 (CASTING Cohort: up to 3.8 years and ENSEMBLE Cohort: up to 5.8 years))
- Percentage Change in White Matter Volume as Detected by Brain MRI Over Time(From Week 8 of CASTING and ENSEMBLE Cohorts up to LIBERTO Week 96 (CASTING Cohort: up to 3.8 years and ENSEMBLE Cohort: up to 5.8 years))
- Percentage Change in Cortical Grey Matter Volume as Detected by Brain MRI Over Time(From Week 8 of CASTING and ENSEMBLE Cohorts up to LIBERTO Week 96 (CASTING Cohort: up to 3.8 years and ENSEMBLE Cohort: up to 5.8 years))
- Time to Treatment Discontinuation(From LIBERTO Baseline to LIBERTO Week 96 (up to 6 years))
- Mean Work Productivity and Activity Impairment (WPAI) Score for CASTING Rollover Cohort(CASTING Baseline to LIBERTO Week 96 (up to 4 years))
- Mean WPAI Score for ENSEMBLE Rollover Cohort(ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years))
- Change From CASTING Baseline in SymptoMScreen Score to LIBERTO Week 96(CASTING Baseline to LIBERTO Week 96 (up to 4 years))
- Change From ENSEMBLE Baseline in SymptoMScreen Score to LIBERTO Week 96(ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years))
- Change From CASTING Baseline in Multiple Sclerosis Impact Scale (MSIS-29), Physical Scale Score to LIBERTO Week 96(CASTING Baseline to LIBERTO Week 96 (up to 4 years))
- Change From ENSEMBLE Baseline in MSIS-29, Physical Scale Score to LIBERTO Week 96(ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years))
- Change From CASTING Baseline in MSIS-29, Psychological Scale Score to LIBERTO Week 96(CASTING Baseline to LIBERTO Week 96 (up to 4 years))
- Change From ENSEMBLE Baseline in MSIS-29, Psychological Scale Score to LIBERTO Week 96(ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years))
- Number of Participants With Adverse Events (AEs)(From CASTING Baseline to LIBERTO SFU (up to 4.9 years); From ENSEMBLE Baseline to LIBERTO SFU (up to 6.9 years))
- Time to first relapse(Up to 2 Years)
- Change in total T1 hypointense lesion volume over time(Up to 2 Years)
- Time to treatment discontinuation/switch(Up to 2 Years)
- Participant reported outcomes: Employment status (Work Productivity and Activity Impairment Questionnaire [WPAI])(Up to 2 Years)
- Total number of FLAIR late enhancing lesions as detected by brain MRI at the end of the treatment period(Up to 2 years)
- Time to first protocol-defined event of disease activity(Up to 2 Years)
- Annualized relapse rate(Up to 2 Years)
- Percentage of participants relapse free, yearly and over the course of the treatment(Up to 2 Years)
- Percentage of participants with no evidence of protocol-defined disease activity (NEDA) yearly and over the duration of the treatment(Up to 2 Years)
- Percentage of participants with no evidence of progression (NEP)(Up to 2 Years)
- Presence and evolution of leptomeningeal follicles as detected by MRI(Up to 2 Years)
- Percentage of participants with no evidence of progression sustained for at least 24 weeks and no active disease (NEPAD)(Up to 2 Years)
- Change from baseline in cognitive performance as measured by the Symbol digit modalities test (SDMT)(Up to 2 Years)
- Total number of T1 Gd-enhancing lesions as detected by brain MRI over time(Up to 2 Years)
- Total number of new and/or enlarging T2 lesion as detected by brain MRI over time(Up to 2 Years)
- Participant reported outcomes: SymptoMScreen Score(Up to 2 Years)
- Participant reported outcomes: Quality of life (QoL) (Multiple Sclerosis Impact Scale [MSIS]-29)(Up to 2 Years)
- Percentage of Participants with Adverse Events(Up to 2 Years)
- Total number of fluid-attenuated inversion-recovery (FLAIR) late enhancing lesions as detected by brain MRI over time(Up to 2 Years)
- Change in brain volume (grey and white matter) as detected by brain MRI over time(Up to 2 Years)