This is an Extension Study of the Roche P-trials to Investigate Safety and Effectiveness of Ocrelizumab in Participants With Multiple Sclerosis (MS)

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

• Ages 18 to 65 years
• All sexes
• No healthy volunteers
• Adult, Older adult

Trial locations and contacts

161 sites in 26 countries.

About this study

Official title: A Single Arm, Open Label Multicentre Extension Study To Evaluate The Effectiveness And Safety Of Ocrelizumab In Patients With Multiple Sclerosis Previously Enrolled In A F. Hoffmann-La Roche Sponsored Ocrelizumab Phase IIIb/IV Clinical Trials

Conditions

Multiple Sclerosis

Being tested

Ocrelizumab

Medical subject headings

Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

• OcrelizumabDrug

  Participants will receive a 600-mg infusion of Ocrelizumab every 24 months for two years.

What is being measured

The primary outcome is the main question the study is designed to answer.

1. 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.

   Measured: From CASTING Baseline to LIBERTO Week 96 (up to 4 years)

2. 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.

   Measured: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)

3. 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.

   Measured: From CASTING Baseline to LIBERTO Week 96 (up to 4 years)

4. 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.

   Measured: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)

5. 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.

   Measured: From CASTING Baseline to LIBERTO Week 96 (up to 4 years)

6. 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.

   Measured: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)

7. 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.

   Measured: From CASTING Baseline to LIBERTO Week 96 (up to 4 years)

8. 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.

   Measured: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)

9. 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.

   Measured: From CASTING Baseline to LIBERTO Week 96 (up to 4 years)

10. 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.

    Measured: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)

11. 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.

    Measured: From CASTING Baseline to LIBERTO Week 96 (up to 4 years)

12. 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.

    Measured: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)

13. 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.

    Measured: At LIBERTO Week 96

14. 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.

    Measured: At LIBERTO Week 96

15. 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).

    Measured: CASTING Baseline to LIBERTO Week 96 (up to 4 years)

16. 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.

    Measured: ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)

17. 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.

    Measured: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)

18. 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.

    Measured: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)

19. 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.

    Measured: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)

20. 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.

    Measured: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)

21. 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.

    Measured: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)

22. 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.

    Measured: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)

23. 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.

    Measured: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)

24. 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.

    Measured: From ENSEMBLE Baseline to LIBERTO Week 96 (up to 6 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted26 Jul 2018
2. Study start12 Jul 2018
3. Primary completion17 Jul 2025
4. Study completion17 Jul 2025

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
• Publications (1)Papers the sponsor has linked to this study.
• Other trials for Multiple SclerosisStudies of the same condition, open and under way.
• More trials run by Hoffmann-La RocheThe sponsor's other registered studies.
• What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.