A Phase 3 interventional study of Ocrelizumab in Multiple Sclerosis, sponsored by Hoffmann-La Roche. Completed at 161 sites in 26 countries. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2026-09-25.
Sponsored by Hoffmann-La Roche · Phase 3, Interventional, and Treatment
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).
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.
3,264 studies on the registry are indexed under Multiple Sclerosis; 659 are open to participants now.
This study's enrollment of 1,055 is above the median of 50 across 2,201 interventional studies indexed under Multiple Sclerosis.
Browse Multiple Sclerosis studies →Hoffmann-La Roche is the lead sponsor of 2,101 studies on the registry; 87 are open to participants now.
Of its 330 completed or terminated interventional studies of FDA-regulated products, 248 (75%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will receive a single 600-mg infusion of Ocrelizumab every 24 weeks up to Week 72 of this study.
Drug: Ocrelizumab
Participants will receive a 600-mg infusion of Ocrelizumab every 24 months for two years.
Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 Weeks From CASTING Baseline to LIBERTO Week 96
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 frame: From CASTING Baseline to LIBERTO Week 96 (up to 4 years)
Time to Onset of CDP Sustained for at Least 24 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
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 frame: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Time to Onset of CDP Sustained for at Least 48 Weeks From CASTING Baseline to LIBERTO Week 96
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 frame: From CASTING Baseline to LIBERTO Week 96 (up to 4 years)
Time to Onset of CDP Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
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.
Time frame: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Percentage of Participants Who Had CDP Sustained for at Least 24 Weeks From CASTING Baseline to LIBERTO Week 96
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.
Time frame: From CASTING Baseline to LIBERTO Week 96 (up to 4 years)
Percentage of Participants Who Had CDP Sustained for at Least 24 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
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.
Time frame: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Percentage of Participants Who Had CDP Sustained for at Least 48 Weeks From CASTING Baseline to LIBERTO Week 96
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.
Time frame: From CASTING Baseline to LIBERTO Week 96 (up to 4 years)
Percentage of Participants Who Had CDP Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
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.
Time frame: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Percentage of Participants Who Had Confirmed Disability Improvement (CDI) Sustained for at Least 24 Weeks From CASTING Baseline to LIBERTO Week 96
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.
Time frame: From CASTING Baseline to LIBERTO Week 96 (up to 4 years)
Percentage of Participants Who Had CDI Sustained for at Least 24 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
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.
Time frame: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Percentage of Participants Who Had CDI Sustained for at Least 48 Weeks From CASTING Baseline to LIBERTO Week 96
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.
Time frame: From CASTING Baseline to LIBERTO Week 96 (up to 4 years)
Percentage of Participants Who Had CDI Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
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.
Time frame: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Percentage of Participants Who Had Improved, Stable or Worsened Disability Compared With CASTING Baseline in EDSS Category 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.
Time frame: At LIBERTO Week 96
Percentage of Participants Who Had Stable or Worsened Disability Compared With ENSEMBLE Baseline in EDSS Category 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.
Time frame: At LIBERTO Week 96
Change From CASTING Baseline in EDSS Score to 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 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).
Time frame: CASTING Baseline to LIBERTO Week 96 (up to 4 years)
Change From ENSEMBLE Baseline in EDSS Score to 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). Estimates are from analysis based on MMRM.
Time frame: ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Time to ≥ 20% Increase in 25-foot Walk Test (T25FWT) Sustained for at Least 24 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
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 frame: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Time to ≥ 20% Increase in 25FWT Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
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 frame: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Time to ≥ 20% Increase in 9 Hole Peg Test (9HPT) Sustained for at Least 24 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
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 frame: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Time to ≥ 20% Increase in 9HPT Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
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.
Time frame: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Percentage of Participants With ≥ 20% Increase in T25FWT Sustained for at Least 24 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
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.
Time frame: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Percentage of Participants With ≥ 20% Increase in T25FWT Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
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.
Time frame: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Percentage of Participants With ≥ 20% Increase in 9HPT Sustained for at Least 24 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
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.
Time frame: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Percentage of Participants With ≥ 20% Increase in 9HPT Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96
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.
Time frame: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Time to First Protocol-Defined Event of Disease Activity
Disease activity was defined as at least one the following events: protocol defined relapse (occurrence of new or worsening neurological symptoms attributable to MS. Symptoms must persist for \> 24 hours and should not be attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications), and immediately be preceded by neurological stability for at least 30 days.); 24 weeks CDP based on increases in EDSS; a new T1 Gadolinium (Gd)-enhanced lesion; or a new and/or enlarging T2 hyperintense lesion on magnetic resonance imaging (MRI). 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 K-M method.
Time frame: 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
A protocol-defined MS relapse is an occurrence of new or worsening neurological symptoms attributable to MS that meets the following criteria: Symptoms persist for \>24 hours and not attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications); Symptoms preceded by neurological stability for at least 30 days; Symptoms accompanied by new objective neurological worsening determined with a timely EDSS/ FSS, 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. The EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death).
Time frame: 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
ARR=total number of relapses for all participants divided by the total years of drug exposure (from first day of infusion in parent study until LIBERTO week 96). Protocol-defined MS relapse=occurrence of new or worsening neurological symptoms attributable to MS that meets the following criteria: Symptoms persist for \>24 hours \& not attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications); Symptoms preceded by neurological stability for at least 30 days; Symptoms accompanied by new objective neurological worsening determined with a timely EDSS/FSS, consistent with an increase of at least: ≥0.5 points on EDSS scale or ≥2 points on 1 of the FSS scales: pyramidal, ambulation, cerebellar, brainstem, sensory, or visual or ≥1 point on 2 or more of the following FSS scales: pyramidal, ambulation, cerebellar, brainstem, sensory, or visual. EDSS scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Adjusted ARR is reported.
Time frame: 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
A protocol-defined MS relapse is an occurrence of new or worsening neurological symptoms attributable to MS that meets the following criteria: Symptoms persist for \>24 hours and not attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications); Symptoms preceded by neurological stability for at least 30 days; Symptoms accompanied by new objective neurological worsening determined with a timely EDSS/ FSS, 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. The EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death).
Time frame: 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
Percentage of participants with NEDA where disease activity = at least 1 of the following events: protocol defined relapse (PDR); 24 weeks CDP based on increases in EDSS while on treatment with ocrelizumab; a T1 Gd-enhanced lesion on MRI; or a new and/or enlarging T2 hyperintense lesion on MRI. PRD as defined in outcome measure 22. CDP= increase of ≥ 1.0 point from EDSS baseline score (BS) when BS was 5.5 or less, and ≥ 0.5 when BS was above 5.5. Participants with EDSS of 0, progression was defined aschange of ≥1.5 points. EDSS is based on a standard neurological examination, incorporating 7 functional systems rated \& scored as FSSs. EDSS disability scale ranges in 0.5-point steps from 0 (normal)-10 (death).
Time frame: From CASTING Baseline to LIBERTO Week 96 (up to 4 years)
Percentage of Participants With NEDA for ENSEMBLE Cohort
Percentage of participants with NEDA where disease activity = at least 1 of the following events: protocol defined relapse (PDR); 24 weeks CDP based on increases in EDSS while on treatment with ocrelizumab; a T1 Gd-enhanced lesion on MRI; or a new and/or enlarging T2 hyperintense lesion on MRI. PRD as defined in outcome measure 22. CDP= increase of ≥ 1.0 point from EDSS baseline score (BS) when BS was 5.5 or less, and ≥ 0.5 when BS was above 5.5. Participants with EDSS of 0, progression was defined aschange of ≥1.5 points. EDSS is based on a standard neurological examination, incorporating 7 functional systems rated \& scored as FSSs. EDSS disability scale ranges in 0.5-point steps from 0 (normal)-10 (death).
Time frame: 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
Percentage of participants with NEP =no progression sustained for at least 24 weeks on: CDP; 20% increase in timed T25FWT; 20% increase in timed 9HPT yearly \& over the course of the study. CDP= increase of ≥ 1.0 point from the baseline EDSS score when BS= 5.5 or less, \& ≥ 0.5 when the BS= above 5.5. For participants with an EDSS of 0, progression=change ≥1.5 points. EDSS is based on a standard neurological examination, incorporating 7 functional systems rated \& scored as FSSs. The EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). In T25FWT test participants walked to a 25 foot course as quickly \& safely as possible. Score = average of 2 completed trials (in seconds). 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. In T25FWT \& 9-HPT the longer it took complete test= higher scores, indicating deterioration.
Time frame: 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
Percentage of participants with NEPAD=no progression on all of the three components of NEP (CDP, T25FWT, 9HPT), no new relapse \& no enlarging or new T2/ T1 Gd-enhancing lesion yearly \& over the course of treatment. CDP= increase of ≥ 1.0 point from EDSS baseline score (BS) when BS= 5.5 or less, \& ≥ 0.5 when BS= above 5.5. Participants with EDSS of 0, progression=change ≥1.5 points. EDSS is based on a standard neurological examination, incorporating 7 functional systems rated \& scored as FSSs. EDSS disability scale ranges in 0.5-point steps from 0 (normal)-10 (death). In T25FWT test participants walked 25-foot course as quickly \& safely as possible. Score = average of 2 completed trials (in seconds). 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. In T25FWT \& 9-HPT the longer it took to complete test= higher scores, indicating deterioration.
Time frame: 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
SDMT test consists of a sequence of 110 symbols to be displayed in a maximum 90 seconds and a reference key legend (3 versions are available) with 9 symbols in a given order and their respective matching digits from 1 to 9. This test measures the speed (number of correct paired responses) to pair abstract symbols with specific digits in 90 seconds time. Responses were collected orally. The score is the number of correctly paired items in 90 seconds with a maximum score of 110 and minimum of 0. Higher scores indicate improvement.
Time frame: 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
SDMT test consists of a sequence of 110 symbols to be displayed in a maximum 90 seconds and a reference key legend (3 versions are available) with 9 symbols in a given order and their respective matching digits from 1 to 9. This test measures the speed (number of correct paired responses) to pair abstract symbols with specific digits in 90 seconds. Responses were collected orally. The score is the number of correctly paired items in 90 seconds with a maximum score of 110 and a minimum of 0. Higher scores indicate improvement.
Time frame: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Rate of Gadolinium-enhancing Lesions on T1Gd+ Lesions as Detected by Brain MRI
The rate was calculated by dividing the total number of T1 Gd-enhanced lesions for all participants by the total number of brain MRI scans. The adjusted rate has been reported, for casting cohort adjusted for duration since MS symptom onset (continuous variable), presence of T1 Gd-enhancing lesions at screening (Yes/No), presence of relapses prior to screening as per the CRF (Yes/No), and number of previous DMTs (≤1 vs. \>1). For ensemble cohort adjusted by presence or absence of T1 lesions count at ENSEMBLE screening and Baseline EDSS category (\<2.5 vs \>=2.5).
Time frame: 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
The rate was calculated by dividing the total number of new and/or enlarging T2 lesions for all participants by the total number of brain MRI scans. The adjusted rate has been reported, for casting cohort adjusted for duration since MS symptom onset (continuous variable), presence of T1 Gd-enhancing lesions at screening (Yes/No), presence of relapses prior to screening as per the CRF (Yes/No), and number of previous DMTs (≤1 vs. \>1). For ensemble cohort adjusted by presence or absence of T1 lesions count at ENSEMBLE screening and Baseline EDSS category (\<2.5 vs \>=2.5).
Time frame: 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
Estimates are from analysis based on mixed-effect model of repeated measures (MMRM)
Time frame: At LIBERTO Week 96
Rate of Fluid-Attenuated Inversion Recovery (FLAIR) Late Enhancing Lesions With Leakage as Detected by Brain MRI Over Time
The rate was calculated by dividing the total number of FLAIR for all participants by the total number of brain MRI scans. The adjusted rate has been reported, for casting cohort adjusted for duration since MS symptom onset (continuous variable), presence of T1 Gd-enhancing lesions at screening (Yes/No), presence of relapses prior to screening as per the CRF (Yes/No), and number of previous DMTs (≤1 vs. \>1). For ensemble cohort adjusted by presence or absence of T1 lesions count at ENSEMBLE screening and Baseline EDSS category (\<2.5 vs \>=2.5).
Time frame: 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
For CASTING cohort percentage change from normalized brain volume at CASTING Week 8 has been reported and for ENSEMBLE cohort percentage change from normalized brain volume at ENSEMBLE week 8 has been reported.
Time frame: 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
For CASTING cohort percentage change from normalized brain volume at CASTING Week 8 has been reported and for ENSEMBLE cohort percentage change from normalized brain volume at ENSEMBLE week 8 has been reported.
Time frame: 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
For CASTING cohort percentage change from normalized brain volume at CASTING Week 8 has been reported and for ENSEMBLE cohort percentage change from normalized brain volume at ENSEMBLE Week 8 has been reported.
Time frame: 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
Time frame: From LIBERTO Baseline to LIBERTO Week 96 (up to 6 years)
Mean Work Productivity and Activity Impairment (WPAI) Score for CASTING Rollover Cohort
The WPAI employment status questionnaire is a PRO consisting of 6 items that assess working status, specifically the impact of MS on absenteeism, presentism, work productivity loss and activity impairment over the past 7 days. Four sub scores are calculated and presented as a percentage. Absenteeism = percent work time missed due to problem; Presenteeism = percent impairment while working due to problem; Work productivity= percent overall work impairment due to problem; Activity Impairment = percent activity Impairment due to problem). These sub-scores are transformed to impairment percentages (range from 0 to 100), with higher numbers indicating greater impairment and less productivity.
Time frame: CASTING Baseline to LIBERTO Week 96 (up to 4 years)
Mean WPAI Score for ENSEMBLE Rollover Cohort
The WPAI employment status questionnaire is a PRO consisting of 6 items that assess working status, specifically the impact of MS on absenteeism, presentism, work productivity loss and activity impairment over the past 7 days. Four sub scores are calculated and presented as a percentage. Absenteeism = percent work time missed due to problem; Presenteeism = percent impairment while working due to problem; Work productivity= percent overall work impairment due to problem; Activity Impairment = percent activity Impairment due to problem). These sub-scores are transformed to impairment percentages (range from 0 to 100), with higher numbers indicating greater impairment and less productivity.
Time frame: ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Change From CASTING Baseline in SymptoMScreen Score to LIBERTO Week 96
The SymptoMScreen comprises 12 distinct domains representing common MS symptoms: mobility, dexterity, vision, fatigue, cognition, bladder function, sensation, dizziness, spasticity, body pain, depression, and anxiety. Limitations associated with each symptom are rated on a 7-point Likert scale ranging from 0 ("not affected at all") to 6 ("total limitation; I am unable to perform most daily activities"). Domain scores are summed to generate a total score ranging from 0 to 72, with higher scores indicating greater symptom-related limitations.
Time frame: CASTING Baseline to LIBERTO Week 96 (up to 4 years)
Change From ENSEMBLE Baseline in SymptoMScreen Score to LIBERTO Week 96
The SymptoMScreen comprises 12 distinct domains representing common MS symptoms: mobility, dexterity, vision, fatigue, cognition, bladder function, sensation, dizziness, spasticity, body pain, depression, and anxiety. Limitations associated with each symptom are rated on a 7-point Likert scale ranging from 0 ("not affected at all") to 6 ("total limitation; I am unable to perform most daily activities"). Domain scores are summed to generate a total score ranging from 0 to 72, with higher scores indicating greater symptom-related limitations.
Time frame: 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
The MSIS-29 version 2 (MSIS-29v2) is a 29-item patient-reported outcome (PRO) measure designed to assess the physical and psychological impact of MS. The Physical Scale consists of 20 items, each rated on a 4-point Likert scale ranging from 1 ("Not at all") to 4 ("Extremely"). Item scores are summed to generate a raw physical impact score, which is then transformed to a 0-100 scale to facilitate interpretation. Lower transformed scores indicate better health-related quality of life (HRQoL).
Time frame: CASTING Baseline to LIBERTO Week 96 (up to 4 years)
Change From ENSEMBLE Baseline in MSIS-29, Physical Scale Score to LIBERTO Week 96
The MSIS-29v2 is a 29-item PRO measure designed to assess the physical and psychological impact of MS. The Physical Scale consists of 20 items, each rated on a 4-point Likert scale ranging from 1 ("Not at all") to 4 ("Extremely"). Item scores are summed to generate a raw physical impact score, which is then transformed to a 0-100 scale to facilitate interpretation. Lower transformed scores indicate better HRQoL.
Time frame: ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Change From CASTING Baseline in MSIS-29, Psychological Scale Score to LIBERTO Week 96
The MSIS-29v2 is a 29-item PRO measure designed to assess the physical and psychological impact of MS. The Psychological Scale consists of 9 items, each rated on a 4-point Likert scale ranging from 1 ("Not at all") to 4 ("Extremely"). Item scores are summed to generate a raw impact score, which is then transformed to a 0-100 scale to facilitate interpretation. Lower transformed scores indicate better HRQoL.
Time frame: CASTING Baseline to LIBERTO Week 96 (up to 4 years)
Change From ENSEMBLE Baseline in MSIS-29, Psychological Scale Score to LIBERTO Week 96
The MSIS-29v2 is a 29-item PRO measure designed to assess the physical and psychological impact of MS. The Psychological Scale consists of 9 items, each rated on a 4-point Likert scale ranging from 1 ("Not at all") to 4 ("Extremely"). Item scores are summed to generate a raw impact score, which is then transformed to a 0-100 scale to facilitate interpretation. Lower transformed scores indicate better HRQoL.
Time frame: ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)
Number of Participants With Adverse Events (AEs)
An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time frame: From CASTING Baseline to LIBERTO SFU (up to 4.9 years); From ENSEMBLE Baseline to LIBERTO SFU (up to 6.9 years)
A total of 1055 participants with Multiple Sclerosis (MS) from CASTING (NCT02861014) and ENSEMBLE (NCT03085810) who were eligible for roll-over based on the investigator decision took part in LIBERTO (NCT03599245) from 12 July 2018 to 17 July 2025.
| Milestone | CASTING Cohort | ENSEMBLE Cohort |
|---|---|---|
| Started | 439 | 616 |
| Completed | 299 | 529 |
| Not completed | 140 | 87 |
| Withdrew: Withdrawal by subject | 16 | 13 |
| Withdrew: Protocol violation | 1 | 0 |
| Withdrew: Pregnancy | 3 | 4 |
| Withdrew: Physician decision | 13 | 7 |
| Withdrew: Reason not specified | 19 | 29 |
| Withdrew: Lost to follow-up | 4 | 4 |
| Withdrew: Lack of efficacy | 1 | 2 |
| Withdrew: Discontinued treatment early & continuing with ocrelizumab outside of study | 4 | 17 |
| Withdrew: Death | 0 | 2 |
| Withdrew: Adverse event | 3 | 9 |
| Withdrew: Discontinued without a discontinuation visit | 1 | 0 |
| Withdrew: Discontinued study due to country-specific early closure of trial | 75 | 0 |
| Milestone | CASTING Cohort | ENSEMBLE Cohort |
|---|---|---|
| Started | 24 | 41 |
| Completed | 17 | 39 |
| Not completed | 7 | 2 |
| Withdrew: Adverse event | 2 | 1 |
| Withdrew: Reason not specified | 3 | 1 |
| Withdrew: Discontinued treatment early & continuing with ocrelizumab outside of study | 2 | 0 |
Disease activity was defined as at least one the following events: protocol defined relapse (occurrence of new or worsening neurological symptoms attributable to MS. Symptoms must persist for \> 24 hours and should not be attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications), and immediately be preceded by neurological stability for at least 30 days.); 24 weeks CDP based on increases in EDSS; a new T1 Gadolinium (Gd)-enhanced lesion; or a new and/or enlarging T2 hyperintense lesion on magnetic resonance imaging (MRI). 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 K-M method.
| weeks | CASTING Cohort | ENSEMBLE Cohort |
|---|---|---|
| Time to First Protocol-Defined Event of Disease Activity | 222.1 (208.9 to NA) | NA (NA to NA) |
A protocol-defined MS relapse is an occurrence of new or worsening neurological symptoms attributable to MS that meets the following criteria: Symptoms persist for \>24 hours and not attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications); Symptoms preceded by neurological stability for at least 30 days; Symptoms accompanied by new objective neurological worsening determined with a timely EDSS/ FSS, 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. The EDSS is a disability scale that ranges in 0.5-point steps from 0 (normal) to 10 (death).
| weeks | CASTING Cohort | ENSEMBLE Cohort |
|---|---|---|
| Time to First Relapse | NA (NA to NA) | NA (NA to NA) |
ARR=total number of relapses for all participants divided by the total years of drug exposure (from first day of infusion in parent study until LIBERTO week 96). Protocol-defined MS relapse=occurrence of new or worsening neurological symptoms attributable to MS that meets the following criteria: Symptoms persist for \>24 hours \& not attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications); Symptoms preceded by neurological stability for at least 30 days; Symptoms accompanied by new objective neurological worsening determined with a timely EDSS/FSS, consistent with an increase of at least: ≥0.5 points on EDSS scale or ≥2 points on 1 of the FSS scales: pyramidal, ambulation, cerebellar, brainstem, sensory, or visual or ≥1 point on 2 or more of the following FSS scales: pyramidal, ambulation, cerebellar, brainstem, sensory, or visual. EDSS scale ranges in 0.5-point steps from 0 (normal) to 10 (death). Adjusted ARR is reported.
| relapse per year | CASTING Cohort | ENSEMBLE Cohort |
|---|---|---|
| Annualized Protocol-Defined Relapse Rate | 0.024 (0.018 to 0.031) | 0.017 (0.012 to 0.022) |
A protocol-defined MS relapse is an occurrence of new or worsening neurological symptoms attributable to MS that meets the following criteria: Symptoms persist for \>24 hours and not attributable to confounding clinical factors (e.g., fever, infection, injury, adverse reactions to medications); Symptoms preceded by neurological stability for at least 30 days; Symptoms accompanied by new objective neurological worsening determined with a timely EDSS/ FSS, 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. The EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death).
| percentage of participants | CASTING Cohort | ENSEMBLE Cohort |
|---|---|---|
| Percentage of Relapse Free Participants | 87.5 (84.0 to 90.4) | 90.9 (88.4 to 93.1) |
Percentage of participants with NEDA where disease activity = at least 1 of the following events: protocol defined relapse (PDR); 24 weeks CDP based on increases in EDSS while on treatment with ocrelizumab; a T1 Gd-enhanced lesion on MRI; or a new and/or enlarging T2 hyperintense lesion on MRI. PRD as defined in outcome measure 22. CDP= increase of ≥ 1.0 point from EDSS baseline score (BS) when BS was 5.5 or less, and ≥ 0.5 when BS was above 5.5. Participants with EDSS of 0, progression was defined aschange of ≥1.5 points. EDSS is based on a standard neurological examination, incorporating 7 functional systems rated \& scored as FSSs. EDSS disability scale ranges in 0.5-point steps from 0 (normal)-10 (death).
| percentage of participants | CASTING Cohort |
|---|---|
| Percentage of Participants With No Protocol-Defined Event of Disease Activity (NEDA) for CASTING Rollover Cohort | 56.8 (51.4 to 62.1) |
Percentage of participants with NEDA where disease activity = at least 1 of the following events: protocol defined relapse (PDR); 24 weeks CDP based on increases in EDSS while on treatment with ocrelizumab; a T1 Gd-enhanced lesion on MRI; or a new and/or enlarging T2 hyperintense lesion on MRI. PRD as defined in outcome measure 22. CDP= increase of ≥ 1.0 point from EDSS baseline score (BS) when BS was 5.5 or less, and ≥ 0.5 when BS was above 5.5. Participants with EDSS of 0, progression was defined aschange of ≥1.5 points. EDSS is based on a standard neurological examination, incorporating 7 functional systems rated \& scored as FSSs. EDSS disability scale ranges in 0.5-point steps from 0 (normal)-10 (death).
| percentage of participants | ENSEMBLE Cohort |
|---|---|
| Percentage of Participants With NEDA for ENSEMBLE Cohort | 27.6 |
Percentage of participants with NEP =no progression sustained for at least 24 weeks on: CDP; 20% increase in timed T25FWT; 20% increase in timed 9HPT yearly \& over the course of the study. CDP= increase of ≥ 1.0 point from the baseline EDSS score when BS= 5.5 or less, \& ≥ 0.5 when the BS= above 5.5. For participants with an EDSS of 0, progression=change ≥1.5 points. EDSS is based on a standard neurological examination, incorporating 7 functional systems rated \& scored as FSSs. The EDSS disability scale ranges in 0.5-point steps from 0 (normal) to 10 (death). In T25FWT test participants walked to a 25 foot course as quickly \& safely as possible. Score = average of 2 completed trials (in seconds). 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. In T25FWT \& 9-HPT the longer it took complete test= higher scores, indicating deterioration.
| percentage of participants | ENSEMBLE Cohort |
|---|---|
| Percentage of Participants With No Evidence of Progression (NEP) From ENSEMBLE Baseline to LIBERTO Week 96 | 36.9 |
Percentage of participants with NEPAD=no progression on all of the three components of NEP (CDP, T25FWT, 9HPT), no new relapse \& no enlarging or new T2/ T1 Gd-enhancing lesion yearly \& over the course of treatment. CDP= increase of ≥ 1.0 point from EDSS baseline score (BS) when BS= 5.5 or less, \& ≥ 0.5 when BS= above 5.5. Participants with EDSS of 0, progression=change ≥1.5 points. EDSS is based on a standard neurological examination, incorporating 7 functional systems rated \& scored as FSSs. EDSS disability scale ranges in 0.5-point steps from 0 (normal)-10 (death). In T25FWT test participants walked 25-foot course as quickly \& safely as possible. Score = average of 2 completed trials (in seconds). 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. In T25FWT \& 9-HPT the longer it took to complete test= higher scores, indicating deterioration.
| percentage of participants | ENSEMBLE Cohort |
|---|---|
| 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 | 45.3 |
SDMT test consists of a sequence of 110 symbols to be displayed in a maximum 90 seconds and a reference key legend (3 versions are available) with 9 symbols in a given order and their respective matching digits from 1 to 9. This test measures the speed (number of correct paired responses) to pair abstract symbols with specific digits in 90 seconds time. Responses were collected orally. The score is the number of correctly paired items in 90 seconds with a maximum score of 110 and minimum of 0. Higher scores indicate improvement.
| scale on score | CASTING Cohort |
|---|---|
| Baseline (CASTING) | 54.5 ± 11.6 |
| Change at LIBERTO Week 96 | 3.0 ± 10.2 |
SDMT test consists of a sequence of 110 symbols to be displayed in a maximum 90 seconds and a reference key legend (3 versions are available) with 9 symbols in a given order and their respective matching digits from 1 to 9. This test measures the speed (number of correct paired responses) to pair abstract symbols with specific digits in 90 seconds. Responses were collected orally. The score is the number of correctly paired items in 90 seconds with a maximum score of 110 and a minimum of 0. Higher scores indicate improvement.
| weeks | ENSEMBLE Cohort |
|---|---|
| Time to 8-point Improvement Change in the SDMT Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96 | NA (NA to NA) |
The rate was calculated by dividing the total number of T1 Gd-enhanced lesions for all participants by the total number of brain MRI scans. The adjusted rate has been reported, for casting cohort adjusted for duration since MS symptom onset (continuous variable), presence of T1 Gd-enhancing lesions at screening (Yes/No), presence of relapses prior to screening as per the CRF (Yes/No), and number of previous DMTs (≤1 vs. \>1). For ensemble cohort adjusted by presence or absence of T1 lesions count at ENSEMBLE screening and Baseline EDSS category (\<2.5 vs \>=2.5).
| adjusted number of lesions per scan | CASTING Cohort | ENSEMBLE Cohort |
|---|---|---|
| Rate of Gadolinium-enhancing Lesions on T1Gd+ Lesions as Detected by Brain MRI | 0.003 (0.002 to 0.006) | 0.005 (0.003 to 0.009) |
The rate was calculated by dividing the total number of new and/or enlarging T2 lesions for all participants by the total number of brain MRI scans. The adjusted rate has been reported, for casting cohort adjusted for duration since MS symptom onset (continuous variable), presence of T1 Gd-enhancing lesions at screening (Yes/No), presence of relapses prior to screening as per the CRF (Yes/No), and number of previous DMTs (≤1 vs. \>1). For ensemble cohort adjusted by presence or absence of T1 lesions count at ENSEMBLE screening and Baseline EDSS category (\<2.5 vs \>=2.5).
| adjusted number of lesions per scan | CASTING Cohort | ENSEMBLE Cohort |
|---|---|---|
| Rate of New or Enlarging T2 Lesions as Detected by Brain MRI | 0.024 (0.018 to 0.032) | 0.021 (0.017 to 0.026) |
Estimates are from analysis based on mixed-effect model of repeated measures (MMRM)
| microliter | CASTING Cohort | ENSEMBLE Cohort |
|---|---|---|
| Change in Total T1 Hypointense Lesion Volume Detected by Brain MRI | -508.6 (-667.38 to -349.87) | -491.463 (-626.637 to -356.290) |
The rate was calculated by dividing the total number of FLAIR for all participants by the total number of brain MRI scans. The adjusted rate has been reported, for casting cohort adjusted for duration since MS symptom onset (continuous variable), presence of T1 Gd-enhancing lesions at screening (Yes/No), presence of relapses prior to screening as per the CRF (Yes/No), and number of previous DMTs (≤1 vs. \>1). For ensemble cohort adjusted by presence or absence of T1 lesions count at ENSEMBLE screening and Baseline EDSS category (\<2.5 vs \>=2.5).
| adjusted number of lesions per scan | CASTING Cohort | ENSEMBLE Cohort |
|---|---|---|
| Rate of Fluid-Attenuated Inversion Recovery (FLAIR) Late Enhancing Lesions With Leakage as Detected by Brain MRI Over Time | 0.032 (0.024 to 0.042) | 0.012 (0.009 to 0.016) |
For CASTING cohort percentage change from normalized brain volume at CASTING Week 8 has been reported and for ENSEMBLE cohort percentage change from normalized brain volume at ENSEMBLE week 8 has been reported.
| percentage change | CASTING Cohort | ENSEMBLE Cohort |
|---|---|---|
| Percentage Change in Brain Volume as Detected by Brain MRI Over Time | -1.588 ± 1.171 | -2.477 ± 1.653 |
For CASTING cohort percentage change from normalized brain volume at CASTING Week 8 has been reported and for ENSEMBLE cohort percentage change from normalized brain volume at ENSEMBLE week 8 has been reported.
| percentage change | CASTING Cohort | ENSEMBLE Cohort |
|---|---|---|
| Percentage Change in White Matter Volume as Detected by Brain MRI Over Time | -1.401 ± 2.454 | -1.248 ± 2.304 |
For CASTING cohort percentage change from normalized brain volume at CASTING Week 8 has been reported and for ENSEMBLE cohort percentage change from normalized brain volume at ENSEMBLE Week 8 has been reported.
| percentage change | CASTING Cohort | ENSEMBLE Cohort |
|---|---|---|
| Percentage Change in Cortical Grey Matter Volume as Detected by Brain MRI Over Time | -0.503 ± 2.783 | -2.180 ± 2.277 |
| weeks | CASTING Cohort | ENSEMBLE Cohort |
|---|---|---|
| Time to Treatment Discontinuation | 121.1 (119.1 to NA) | NA (NA to NA) |
The WPAI employment status questionnaire is a PRO consisting of 6 items that assess working status, specifically the impact of MS on absenteeism, presentism, work productivity loss and activity impairment over the past 7 days. Four sub scores are calculated and presented as a percentage. Absenteeism = percent work time missed due to problem; Presenteeism = percent impairment while working due to problem; Work productivity= percent overall work impairment due to problem; Activity Impairment = percent activity Impairment due to problem). These sub-scores are transformed to impairment percentages (range from 0 to 100), with higher numbers indicating greater impairment and less productivity.
| score percentage | CASTING Cohort |
|---|---|
| Absenteeism: CASTING Baseline | 10.30 ± 26.66 |
| Absenteeism: LIBERTO Week 96 | 3.61 ± 12.63 |
| Presenteeism: CASTING Baseline | 19.85 ± 22.32 |
| Presenteeism: LIBERTO Week 96 | 14.44 ± 19.18 |
| Work Productivity: CASTING Baseline | 22.94 ± 26.74 |
| Work Productivity: LIBERTO Week 96 | 16.52 ± 21.41 |
| Activity Impairment: CASTING Baseline | 29.71 ± 27.72 |
| Activity Impairment: LIBERTO Week 96 | 22.93 ± 26.51 |
The WPAI employment status questionnaire is a PRO consisting of 6 items that assess working status, specifically the impact of MS on absenteeism, presentism, work productivity loss and activity impairment over the past 7 days. Four sub scores are calculated and presented as a percentage. Absenteeism = percent work time missed due to problem; Presenteeism = percent impairment while working due to problem; Work productivity= percent overall work impairment due to problem; Activity Impairment = percent activity Impairment due to problem). These sub-scores are transformed to impairment percentages (range from 0 to 100), with higher numbers indicating greater impairment and less productivity.
| score percentage | ENSEMBLE Cohort |
|---|---|
| Absenteeism: ENSEMBLE Baseline | 19.78 ± 36.60 |
| Absenteeism: LIBERTO Week 96 | 3.93 ± 13.23 |
| Presenteeism: ENSEMBLE Baseline | 17.88 ± 22.95 |
| Presenteeism: LIBERTO Week 96 | 14.11 ± 19.31 |
| Work Productivity: ENSEMBLE Baseline | 26.42 ± 32.18 |
| Work Productivity: LIBERTO Week 96 | 16.25 ± 22.01 |
| Activity Impairment: ENSEMBLE Baseline | 23.09 ± 24.24 |
| Activity Impairment: LIBERTO Week 96 | 18.28 ± 23.41 |
The SymptoMScreen comprises 12 distinct domains representing common MS symptoms: mobility, dexterity, vision, fatigue, cognition, bladder function, sensation, dizziness, spasticity, body pain, depression, and anxiety. Limitations associated with each symptom are rated on a 7-point Likert scale ranging from 0 ("not affected at all") to 6 ("total limitation; I am unable to perform most daily activities"). Domain scores are summed to generate a total score ranging from 0 to 72, with higher scores indicating greater symptom-related limitations.
| scale on score | CASTING Cohort |
|---|---|
| Baseline (CASTING) | 14.4 ± 12.4 |
| Change at LIBERTO Week 96 | -1.8 ± 9.6 |
The SymptoMScreen comprises 12 distinct domains representing common MS symptoms: mobility, dexterity, vision, fatigue, cognition, bladder function, sensation, dizziness, spasticity, body pain, depression, and anxiety. Limitations associated with each symptom are rated on a 7-point Likert scale ranging from 0 ("not affected at all") to 6 ("total limitation; I am unable to perform most daily activities"). Domain scores are summed to generate a total score ranging from 0 to 72, with higher scores indicating greater symptom-related limitations.
| scale on score | ENSEMBLE Cohort |
|---|---|
| Baseline (ENSEMBLE) | 12.3 ± 10.6 |
| Change at LIBERTO Week 96 | -0.6 ± 10.4 |
The MSIS-29 version 2 (MSIS-29v2) is a 29-item patient-reported outcome (PRO) measure designed to assess the physical and psychological impact of MS. The Physical Scale consists of 20 items, each rated on a 4-point Likert scale ranging from 1 ("Not at all") to 4 ("Extremely"). Item scores are summed to generate a raw physical impact score, which is then transformed to a 0-100 scale to facilitate interpretation. Lower transformed scores indicate better health-related quality of life (HRQoL).
| scale on score | CASTING Cohort |
|---|---|
| Baseline (CASTING) | 21.16 ± 20.60 |
| Change at LIBERTO Week 96 | -2.40 ± 16.27 |
The MSIS-29v2 is a 29-item PRO measure designed to assess the physical and psychological impact of MS. The Physical Scale consists of 20 items, each rated on a 4-point Likert scale ranging from 1 ("Not at all") to 4 ("Extremely"). Item scores are summed to generate a raw physical impact score, which is then transformed to a 0-100 scale to facilitate interpretation. Lower transformed scores indicate better HRQoL.
| scale on score | ENSEMBLE Cohort |
|---|---|
| Baseline (ENSEMBLE) | 17.40 ± 18.37 |
| Change at LIBERTO Week 96 | -0.31 ± 17.78 |
The MSIS-29v2 is a 29-item PRO measure designed to assess the physical and psychological impact of MS. The Psychological Scale consists of 9 items, each rated on a 4-point Likert scale ranging from 1 ("Not at all") to 4 ("Extremely"). Item scores are summed to generate a raw impact score, which is then transformed to a 0-100 scale to facilitate interpretation. Lower transformed scores indicate better HRQoL.
| scale on score | CASTING Cohort |
|---|---|
| Baseline (CASTING) | 32.03 ± 23.68 |
| Change at LIBERTO Week 96 | -8.32 ± 19.94 |
The MSIS-29v2 is a 29-item PRO measure designed to assess the physical and psychological impact of MS. The Psychological Scale consists of 9 items, each rated on a 4-point Likert scale ranging from 1 ("Not at all") to 4 ("Extremely"). Item scores are summed to generate a raw impact score, which is then transformed to a 0-100 scale to facilitate interpretation. Lower transformed scores indicate better HRQoL.
| scale on score | ENSEMBLE Cohort |
|---|---|
| Baseline (ENSEMBLE) | 29.48 ± 21.99 |
| Change at LIBERTO Week 96 | -6.02 ± 23.35 |
An AE was any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
| Participants | CASTING Cohort | ENSEMBLE Cohort |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | 408 | 598 |
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.
| weeks | CASTING Cohort |
|---|---|
| Time to Onset of Confirmed Disability Progression (CDP) Sustained for at Least 24 Weeks From CASTING Baseline to LIBERTO Week 96 | 222.1 (222.1 to NA) |
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.
| weeks | ENSEMBLE Cohort |
|---|---|
| Time to Onset of CDP Sustained for at Least 24 Weeks From ENSEMBLE Baseline to LIBERTO Week 96 | NA (NA to NA) |
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.
| weeks | CASTING Cohort |
|---|---|
| Time to Onset of CDP Sustained for at Least 48 Weeks From CASTING Baseline to LIBERTO Week 96 | 222.1 (222.1 to NA) |
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.
| weeks | ENSEMBLE Cohort |
|---|---|
| Time to Onset of CDP Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96 | NA (NA to NA) |
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 | CASTING Cohort |
|---|---|
| Percentage of Participants Who Had CDP Sustained for at Least 24 Weeks From CASTING Baseline to LIBERTO Week 96 | 20.5 |
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 | ENSEMBLE Cohort |
|---|---|
| Percentage of Participants Who Had CDP Sustained for at Least 24 Weeks From ENSEMBLE Baseline to LIBERTO Week 96 | 15.1 |
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 | CASTING Cohort |
|---|---|
| Percentage of Participants Who Had CDP Sustained for at Least 48 Weeks From CASTING Baseline to LIBERTO Week 96 | 18.9 |
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 | ENSEMBLE Cohort |
|---|---|
| Percentage of Participants Who Had CDP Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96 | 11.0 |
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 | CASTING Cohort |
|---|---|
| Percentage of Participants Who Had Confirmed Disability Improvement (CDI) Sustained for at Least 24 Weeks From CASTING Baseline to LIBERTO Week 96 | 24.0 (18.7 to 29.9) |
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 | ENSEMBLE Cohort |
|---|---|
| Percentage of Participants Who Had CDI Sustained for at Least 24 Weeks From ENSEMBLE Baseline to LIBERTO Week 96 | 40.3 |
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 | CASTING Cohort |
|---|---|
| Percentage of Participants Who Had CDI Sustained for at Least 48 Weeks From CASTING Baseline to LIBERTO Week 96 | 20.7 (15.7 to 26.3) |
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 | ENSEMBLE Cohort |
|---|---|
| Percentage of Participants Who Had CDI Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96 | 32.8 |
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 | CASTING Cohort |
|---|---|
| Worsened (>0.5) | 18.7 |
| Stable (-0.5, 0 ,0.5) | 65.9 |
| Improved (<-0.5) | 15.4 |
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.
| percentage of participants | ENSEMBLE Cohort |
|---|---|
| Worsened (>0.5) | 11 |
| Stable (-0.5, 0 ,0.5) | 89 |
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).
| score on scale | CASTING Cohort |
|---|---|
| Change From CASTING Baseline in EDSS Score to LIBERTO Week 96 | 0.12 ± 0.07 |
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.
| score on scale | ENSEMBLE Cohort |
|---|---|
| Change From ENSEMBLE Baseline in EDSS Score to LIBERTO Week 96 | -0.119 ± 0.059 |
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.
| weeks | ENSEMBLE Cohort |
|---|---|
| Time to ≥ 20% Increase in 25-foot Walk Test (T25FWT) Sustained for at Least 24 Weeks From ENSEMBLE Baseline to LIBERTO Week 96 | NA (NA to NA) |
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.
| weeks | ENSEMBLE Cohort |
|---|---|
| Time to ≥ 20% Increase in 25FWT Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96 | NA (NA to NA) |
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.
| weeks | ENSEMBLE Cohort |
|---|---|
| Time to ≥ 20% Increase in 9 Hole Peg Test (9HPT) Sustained for at Least 24 Weeks From ENSEMBLE Baseline to LIBERTO Week 96 | NA (NA to NA) |
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.
| weeks | ENSEMBLE Cohort |
|---|---|
| Time to ≥ 20% Increase in 9HPT Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96 | NA (NA to NA) |
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 | ENSEMBLE Cohort |
|---|---|
| Percentage of Participants With ≥ 20% Increase in T25FWT Sustained for at Least 24 Weeks From ENSEMBLE Baseline to LIBERTO Week 96 | 24.4 |
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 | ENSEMBLE Cohort |
|---|---|
| Percentage of Participants With ≥ 20% Increase in T25FWT Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96 | 17.7 |
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 | ENSEMBLE Cohort |
|---|---|
| Percentage of Participants With ≥ 20% Increase in 9HPT Sustained for at Least 24 Weeks From ENSEMBLE Baseline to LIBERTO Week 96 | 9.4 |
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.
| percentage of participants | ENSEMBLE Cohort |
|---|---|
| Percentage of Participants With ≥ 20% Increase in 9HPT Sustained for at Least 48 Weeks From ENSEMBLE Baseline to LIBERTO Week 96 | 6.5 |
Collected over From CASTING Baseline to LIBERTO SFU (up to 4.9 years); From ENSEMBLE Baseline to LIBERTO SFU (up to 6.9 years). Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| CASTING Cohort | 0/439 (0%) | 41/439 (9.3%) | 366/439 (83.4%) |
| ENSEMBLE Cohort | 2/616 (0.3%) | 109/616 (17.7%) | 577/616 (93.7%) |
| Event | CASTING Cohort | ENSEMBLE Cohort |
|---|---|---|
| COVID-19 PNEUMONIAInfections and infestations | 1/439 | 16/616 |
| COVID-19Infections and infestations | 0/439 | 10/616 |
| ABORTION SPONTANEOUSPregnancy, puerperium and perinatal conditions | 1/439 | 6/616 |
| SINUSITISInfections and infestations | 3/439 | 0/616 |
| PNEUMONIAInfections and infestations | 0/439 | 4/616 |
| PYELONEPHRITISInfections and infestations | 0/439 | 3/616 |
| ABORTION INDUCEDSurgical and medical procedures | 0/439 | 3/616 |
| BREAST CANCERNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 2/439 | 0/616 |
| NEUTROPENIABlood and lymphatic system disorders | 0/439 | 2/616 |
| ABDOMINAL PAIN UPPERGastrointestinal disorders | 0/439 | 2/616 |
| Event | CASTING Cohort | ENSEMBLE Cohort |
|---|---|---|
| INFUSION RELATED REACTIONInjury, poisoning and procedural complications | 194/439 | 339/616 |
| COVID-19Infections and infestations | 6/439 | 313/616 |
| NASOPHARYNGITISInfections and infestations | 126/439 | 174/616 |
| HEADACHENervous system disorders | 100/439 | 159/616 |
| UPPER RESPIRATORY TRACT INFECTIONInfections and infestations | 38/439 | 130/616 |
| URINARY TRACT INFECTIONInfections and infestations | 69/439 | 120/616 |
| INFLUENZAInfections and infestations | 81/439 | 64/616 |
| FATIGUEGeneral disorders | 43/439 | 101/616 |
| ARTHRALGIAMusculoskeletal and connective tissue disorders | 31/439 | 83/616 |
| COUGHRespiratory, thoracic and mediastinal disorders | 41/439 | 77/616 |
Intent-to-Treat (ITT) population included all enrolled participants who received any dose of ocrelizumab.
| Age, Categorical(Participants) | CASTING Cohort | ENSEMBLE Cohort | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 439 | 616 | 1055 |
| >=65 years | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | CASTING Cohort | ENSEMBLE Cohort | Total |
|---|---|---|---|
| Female | 276 | 383 | 659 |
| Male | 163 | 233 | 396 |
| Ethnicity (NIH/OMB)(Participants) | CASTING Cohort | ENSEMBLE Cohort | Total |
|---|---|---|---|
| Hispanic or Latino | 17 | 73 | 90 |
| Not Hispanic or Latino | 383 | 242 | 625 |
| Unknown or Not Reported | 39 | 8 | 47 |
| Race (NIH/OMB)(Participants) | CASTING Cohort | ENSEMBLE Cohort | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 10 | 10 |
| Asian | 2 | 7 | 9 |
| Native Hawaiian or Other Pacific Islander | 0 | 1 | 1 |
| Black or African American | 1 | 4 | 5 |
| White | 402 | 263 | 665 |
| More than one race | 0 | 17 | 17 |
| Unknown or Not Reported | 34 | 21 | 55 |
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Plan to share: Yes — For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing
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Studies of the drug tested here: Ocrelizumab