Ignite Creation Date:
2024-05-06 @ 5:10 PM
Last Modification Date:
2024-10-26 @ 2:23 PM
Study NCT ID:
NCT05210621
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2024-05-17
First Post:
2022-01-14
Brief Title:
LONG-TERM EFFECTIVENESS AND SAFETY EVALUATION OF OCRELIZUMAB
Sponsor:
Centre Hospitalier Universitaire de Nice
Organization:
Centre Hospitalier Universitaire de Nice
Study Overview
Official Title:
LONG-TERM EFFECTIVENESS AND SAFETY EVALUATION OF OCRELIZUMAB IN FRENCH PATIENTS WITH PROGRESSIVE MS CONSONANCE EXTENSION STUDY
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CONSONANCE EX
Brief Summary:
The study duration of 4 years was considered to be sufficient to show a reliable and relevant effect of ocrelizumab on disability progression in the main study CONSONANCE However given the potential long-term use of ocrelizumab in patients with progressive MS it is critical that additional effectiveness and safety data are accrued in this patient population In particular understanding how ocrelizumab can prevent or delay time to major disability milestones such as the need to use an assisting device Expanded Disability Status Scale EDSS 60 or a wheelchair EDSS 70 is of significant relevance given that progression to such milestones is associated with a significant reduction in patients quality of life and an increase in cost of treatment Kobelt et al 2017
In the ORATORIO trial ocrelizumab reduced the risk of 24-week confirmed EDSS 70 by 46 hazard ratio HR 054 95 CI 031-092 p 0022 in patients with primary progressive multiple sclerosis PPMS To further characterize the potential long-term impact of ocrelizumab treatment on time to 24-week confirmed EDSS 70 an analysis was used to extrapolate the observed data into the future estimating the time at which 50 of patients were expected to have reached EDSS 70 Extrapolated median time to confirmed EDSS 70 was 121 years for placebo which was similar to the actual median time observed in MSBase 124 years and 192 years for ocrelizumab representing a 71-year delay 95 CI -43 to 184 Butzkueven et al 2021 A recent MSBase analysis also showed that in a cohort of patients with secondary progressive MS SPMS 179 reached a confirmed EDSS score of 70 from the diagnosis of SPMS over a period of approximately 12 years Lizak et al 2020 Therefore following patients who complete CONSONANCE beyond the 4-year study period is justified to better assess the impact of ocrelizumab on these long-term disability milestones
Another important therapeutic clinical goal in patients with progressive MS is preserving upper limb function Patients with progressive MS with high EDSS scores including those who are wheelchair-restricted experience a devastating reduction in quality of life if they lose any residual function in their arms andor hands as this affects the level of independence and significantly limits the ability to perform activities of daily living Kraft et al 2014 The Nine-Hole Peg Test 9-HPT has become one of the most frequently used measures of upper extremity function in MS Earhart et al 2011 A 20 worsening in test time is commonly used to define clinically meaningful worsening as it corresponds to predefined clinically significant changes of established clinician- and patient-reported measures Feys et al 2017 Progression rates are lower for 9-HPT compared to EDSS or the Timed 25-Foot Walk Test 25FWT Goldman et al 2019 Therefore following patients who complete CONSONANCE beyond the 4 year study period is justified to better assess the long-term impact of ocrelizumab on preserving upper limb function
Patients with MS who have completed the CONSONANCE study and have a favorable benefit risk ratio as determined by the treating neurologist can be included in this study if they meet the inclusion and exclusion criteria
11 Study design
This is a 4-year single-arm open-label multicenter study for patients who have completed 192 weeks of treatment with ocrelizumab in the CONSONANCE study NCT03523858 and enrolled under the protocol version 1 of CONSONANCE It is estimated that the study will enroll approximately 90 patients with progressive MS The study will consist of the following periods
1 Screening period The screening visit should be scheduled up to two weeks before the first infusion of ocrelizumab and always after the last visit of CONSONANCE at Week 192 This period should not be exceeded
2 Treatment period The first visit of the treatment period first infusion of ocrelizumab will occur at the baseline visit which should be 24 weeks 14 days after the last infusion of ocrelizumab in CONSONANCE Ocrelizumab will be administered every 24 weeks up to Week 168 of this study The last visit in the treatment period will be conducted 24 weeks after the last dose of ocrelizumab ie at Week 192
In the ORATORIO trial ocrelizumab reduced the risk of 24-week confirmed EDSS 70 by 46 hazard ratio HR 054 95 CI 031-092 p 0022 in patients with primary progressive multiple sclerosis PPMS To further characterize the potential long-term impact of ocrelizumab treatment on time to 24-week confirmed EDSS 70 an analysis was used to extrapolate the observed data into the future estimating the time at which 50 of patients were expected to have reached EDSS 70 Extrapolated median time to confirmed EDSS 70 was 121 years for placebo which was similar to the actual median time observed in MSBase 124 years and 192 years for ocrelizumab representing a 71-year delay 95 CI -43 to 184 Butzkueven et al 2021 A recent MSBase analysis also showed that in a cohort of patients with secondary progressive MS SPMS 179 reached a confirmed EDSS score of 70 from the diagnosis of SPMS over a period of approximately 12 years Lizak et al 2020 Therefore following patients who complete CONSONANCE beyond the 4-year study period is justified to better assess the impact of ocrelizumab on these long-term disability milestones
Another important therapeutic clinical goal in patients with progressive MS is preserving upper limb function Patients with progressive MS with high EDSS scores including those who are wheelchair-restricted experience a devastating reduction in quality of life if they lose any residual function in their arms andor hands as this affects the level of independence and significantly limits the ability to perform activities of daily living Kraft et al 2014 The Nine-Hole Peg Test 9-HPT has become one of the most frequently used measures of upper extremity function in MS Earhart et al 2011 A 20 worsening in test time is commonly used to define clinically meaningful worsening as it corresponds to predefined clinically significant changes of established clinician- and patient-reported measures Feys et al 2017 Progression rates are lower for 9-HPT compared to EDSS or the Timed 25-Foot Walk Test 25FWT Goldman et al 2019 Therefore following patients who complete CONSONANCE beyond the 4 year study period is justified to better assess the long-term impact of ocrelizumab on preserving upper limb function
Patients with MS who have completed the CONSONANCE study and have a favorable benefit risk ratio as determined by the treating neurologist can be included in this study if they meet the inclusion and exclusion criteria
11 Study design
This is a 4-year single-arm open-label multicenter study for patients who have completed 192 weeks of treatment with ocrelizumab in the CONSONANCE study NCT03523858 and enrolled under the protocol version 1 of CONSONANCE It is estimated that the study will enroll approximately 90 patients with progressive MS The study will consist of the following periods
1 Screening period The screening visit should be scheduled up to two weeks before the first infusion of ocrelizumab and always after the last visit of CONSONANCE at Week 192 This period should not be exceeded
2 Treatment period The first visit of the treatment period first infusion of ocrelizumab will occur at the baseline visit which should be 24 weeks 14 days after the last infusion of ocrelizumab in CONSONANCE Ocrelizumab will be administered every 24 weeks up to Week 168 of this study The last visit in the treatment period will be conducted 24 weeks after the last dose of ocrelizumab ie at Week 192
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None