LONG-TERM EFFECTIVENESS AND SAFETY EVALUATION OF OCRELIZUMAB (CONSONANCE EX)
Primary Purpose
Multiple Sclerosis
Status
Recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Ocrelizumab
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis
Eligibility Criteria
Inclusion Criteria:
- Signed informed consent form
- Able to comply with the study protocol, in the investigator's judgment
- Affiliation to the social security system
- Completed the treatment period of Roche-sponsored ocrelizumab trial (CONSONANCE) and who in the opinion of the investigator may benefit from treatment with ocrelizumab. Only patients enrolled under Protocol version 1 (approval date: 18 February 2018) will be eligible.
- Meet re-treatment criteria with ocrelizumab (please see section 6.11)
- Patients who became pregnant by chance between the last visit of the CONSONANCE study and screening of this study, as confirmed by pregnancy tests at screening, will enter the study but will only re-start treatment with ocrelizumab after birth or after breastfeeding is stopped, as per re-treatment criteria in section 6.11
Women of childbearing potential* (WOCBP):
- Must have a negative urine pregnancy test at Visit 1 (Screening) and Visit 2 (Baseline)
- Must agree to remain abstinent or use an acceptable birth control method during the treatment period and for at least 6 months or longer after the final dose of ocrelizumab, as applicable in the ocrelizumab package leaflet. The following contraceptive methods are considered acceptable (failure rate >1% [Clinical Trial Facilitation Group (CTFG)]): (1) progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action; (2) male or female condom with or without spermicide; (3) cap, diaphragm, or sponge with spermicide; (4) combination of male condom with cap, diaphragm, or sponge with spermicide (double-barrier method). Birth control methods that are highly effective (i.e. failure rate <1% [CTFG]) may also be used but are not required, and include: (1) oral, intravaginal or transdermal combined hormonal contraception associated with inhibition of ovulation; (2) oral, injectable or implantable progestogen-only hormonal contraception associated with inhibition of ovulation; (3) intrauterine device; (4) intrauterine hormone-releasing system; (5) bilateral tubal occlusion; (6) vasectomized partner; (7) sexual abstinence.
Exclusion Criteria:
- Hypersensitivity to ocrelizumab or any of its excipients
- Patients in a severely immunocompromised state, until the condition resolves
- Evidence of any adverse event (AE) potentially attributable to ocrelizumab, for which the local label recommends permanent discontinuation
- Existence of a contra-indication as per the Summary of Product Characteristics (SmPC)
- Prohibited concomitant medication as specified in section 6.7
- Patients intending to become pregnant during the study or within 6 months after the last dose of the study drug in CONSONANCE
- Patients who had early ocrelizumab discontinuation in CONSONANCE (exemption made for treatment discontinuation due to unplanned pregnancy and breastfeeding for patients who continued clinical study assessments in CONSONANCE)
Sites / Locations
- Amiens University Hospital
- Bayonne Hospital
- Bordeaux University Hospital
- Caen University Hospital
- Clermont ferrand University Hospital
- Lille University Hospital
- Lyon University Hospital
- Marseille Univesity Hospital
- Montpellier University Hospital
- Nancy University HospitalRecruiting
- Nantes University hospital
- Nice University HospitalRecruiting
- Nimes University Hospital
- Rennes University Hospital
- Strasbourg University Hospital
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
Patients with MS who have completed the CONSONANCE study
Arm Description
Outcomes
Primary Outcome Measures
Proportion of patients with upper limb disability progression
Proportion of patients with upper limb disability progression, defined as the proportion of patients with ≥20% worsening in 9 HPT score confirmed for at least 24 weeks,
Proportion of patients with upper limb disability progression
Proportion of patients with upper limb disability progression, defined as the proportion of patients with ≥20% worsening in 9 HPT score confirmed for at least 24 weeks,
Secondary Outcome Measures
Full Information
NCT ID
NCT05210621
First Posted
January 14, 2022
Last Updated
July 12, 2022
Sponsor
Centre Hospitalier Universitaire de Nice
1. Study Identification
Unique Protocol Identification Number
NCT05210621
Brief Title
LONG-TERM EFFECTIVENESS AND SAFETY EVALUATION OF OCRELIZUMAB
Acronym
CONSONANCE EX
Official Title
LONG-TERM EFFECTIVENESS AND SAFETY EVALUATION OF OCRELIZUMAB IN FRENCH PATIENTS WITH PROGRESSIVE MS: CONSONANCE EXTENSION STUDY
Study Type
Interventional
2. Study Status
Record Verification Date
January 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 8, 2022 (Actual)
Primary Completion Date
February 24, 2026 (Anticipated)
Study Completion Date
February 24, 2029 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Nice
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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] 6.0) or a wheelchair (EDSS ≥7.0) 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 ≥7.0 by 46% (hazard ratio [HR]: 0.54, 95% CI 0.31-0.92; p = 0.022) 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 ≥7.0, 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 ≥7.0. Extrapolated median time to confirmed EDSS ≥7.0 was 12.1 years for placebo, which was similar to the actual median time observed in MSBase (12.4 years), and 19.2 years for ocrelizumab, representing a 7.1-year delay (95% CI: -4.3 to 18.4) [Butzkueven et al 2021]. A recent MSBase analysis also showed that in a cohort of patients with secondary progressive MS (SPMS), 17.9% reached a confirmed EDSS score of 7.0 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 and/or 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.
1.1. 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:
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.
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 (i.e., at Week 192).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
89 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Patients with MS who have completed the CONSONANCE study
Arm Type
Other
Intervention Type
Drug
Intervention Name(s)
Ocrelizumab
Intervention Description
ocrelizumab will be administered as single 600-mg infusions in 500 mL 0.9% sodium chloride every 24 weeks (±14 days) up to Week 192 (Year 4) of this study
Primary Outcome Measure Information:
Title
Proportion of patients with upper limb disability progression
Description
Proportion of patients with upper limb disability progression, defined as the proportion of patients with ≥20% worsening in 9 HPT score confirmed for at least 24 weeks,
Time Frame
baseline
Title
Proportion of patients with upper limb disability progression
Description
Proportion of patients with upper limb disability progression, defined as the proportion of patients with ≥20% worsening in 9 HPT score confirmed for at least 24 weeks,
Time Frame
week 192.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Signed informed consent form
Able to comply with the study protocol, in the investigator's judgment
Affiliation to the social security system
Completed the treatment period of Roche-sponsored ocrelizumab trial (CONSONANCE) and who in the opinion of the investigator may benefit from treatment with ocrelizumab. Only patients enrolled under Protocol version 1 (approval date: 18 February 2018) will be eligible.
Meet re-treatment criteria with ocrelizumab (please see section 6.11)
Patients who became pregnant by chance between the last visit of the CONSONANCE study and screening of this study, as confirmed by pregnancy tests at screening, will enter the study but will only re-start treatment with ocrelizumab after birth or after breastfeeding is stopped, as per re-treatment criteria in section 6.11
Women of childbearing potential* (WOCBP):
Must have a negative urine pregnancy test at Visit 1 (Screening) and Visit 2 (Baseline)
Must agree to remain abstinent or use an acceptable birth control method during the treatment period and for at least 6 months or longer after the final dose of ocrelizumab, as applicable in the ocrelizumab package leaflet. The following contraceptive methods are considered acceptable (failure rate >1% [Clinical Trial Facilitation Group (CTFG)]): (1) progestogen-only oral hormonal contraception, where inhibition of ovulation is not the primary mode of action; (2) male or female condom with or without spermicide; (3) cap, diaphragm, or sponge with spermicide; (4) combination of male condom with cap, diaphragm, or sponge with spermicide (double-barrier method). Birth control methods that are highly effective (i.e. failure rate <1% [CTFG]) may also be used but are not required, and include: (1) oral, intravaginal or transdermal combined hormonal contraception associated with inhibition of ovulation; (2) oral, injectable or implantable progestogen-only hormonal contraception associated with inhibition of ovulation; (3) intrauterine device; (4) intrauterine hormone-releasing system; (5) bilateral tubal occlusion; (6) vasectomized partner; (7) sexual abstinence.
Exclusion Criteria:
Hypersensitivity to ocrelizumab or any of its excipients
Patients in a severely immunocompromised state, until the condition resolves
Evidence of any adverse event (AE) potentially attributable to ocrelizumab, for which the local label recommends permanent discontinuation
Existence of a contra-indication as per the Summary of Product Characteristics (SmPC)
Prohibited concomitant medication as specified in section 6.7
Patients intending to become pregnant during the study or within 6 months after the last dose of the study drug in CONSONANCE
Patients who had early ocrelizumab discontinuation in CONSONANCE (exemption made for treatment discontinuation due to unplanned pregnancy and breastfeeding for patients who continued clinical study assessments in CONSONANCE)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Céline CALLIER
Phone
33 4 92 03 78 98
Email
callier.c@chu-nice.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Christine Lebrun-Frenay
Phone
33 4 92 03 78 98
Email
lebrun-frenay.c@chu-nice.fr
Facility Information:
Facility Name
Amiens University Hospital
City
Amiens
ZIP/Postal Code
80051
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Abdullatif AL KHEDR
Email
alkhedr.abdullatif@chu-amiens.fr
First Name & Middle Initial & Last Name & Degree
Abdullatif AL KHEDR
Facility Name
Bayonne Hospital
City
Bayonne
ZIP/Postal Code
64100
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patricia Bernady
Email
pbernady@ch-cotebasque.fr
First Name & Middle Initial & Last Name & Degree
Patricia Bernady
Facility Name
Bordeaux University Hospital
City
Bordeaux
ZIP/Postal Code
33076
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aurelie Ruet
Email
aurelie.ruet@chu-bordeaux.fr
First Name & Middle Initial & Last Name & Degree
Aurelie Ruet
Facility Name
Caen University Hospital
City
Caen
ZIP/Postal Code
14033
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
pierre Branger
Email
branger-p@chu-caen.fr
First Name & Middle Initial & Last Name & Degree
Pierre Branger
Facility Name
Clermont ferrand University Hospital
City
Clermont-Ferrand
ZIP/Postal Code
63003
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pierre Clavelou
Email
pclavelou@chu-clermontferrand.fr
First Name & Middle Initial & Last Name & Degree
Pierre Clavelou
Facility Name
Lille University Hospital
City
Lille
ZIP/Postal Code
59037
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patrick Vermersch
Email
patrick.vermersch@univ-lille2.fr
First Name & Middle Initial & Last Name & Degree
Patrick Vermersch
Facility Name
Lyon University Hospital
City
Lyon
ZIP/Postal Code
69677
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
sandra Vukusic
Email
sandra.vukusic@chu-lyon.fr
First Name & Middle Initial & Last Name & Degree
Sandra Vukusic
Facility Name
Marseille Univesity Hospital
City
Marseille
ZIP/Postal Code
13385
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jean Pelletier
Email
Jean.PELLETIER@ap-hm.fr
First Name & Middle Initial & Last Name & Degree
Jean Pelletier
Facility Name
Montpellier University Hospital
City
Montpellier
ZIP/Postal Code
34295
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pierre Labauge
Email
labauge@yahoo.fr
First Name & Middle Initial & Last Name & Degree
pierre labauge
Facility Name
Nancy University Hospital
City
Nancy
ZIP/Postal Code
54000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guillaume Mathey
Email
gmathey@chru-nancy.fr
First Name & Middle Initial & Last Name & Degree
guillaume Mathey
Facility Name
Nantes University hospital
City
Nantes
ZIP/Postal Code
42055
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
david Laplaud
Email
david.laplaud@univ-nantes.fr
First Name & Middle Initial & Last Name & Degree
David Laplaud
Facility Name
Nice University Hospital
City
Nice
ZIP/Postal Code
06000
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Céline CALLIER
Phone
33 4 92 03 78 98
Email
callier.c@chu-nice.Fr
First Name & Middle Initial & Last Name & Degree
Christine LEBRIN-FRENAY
Phone
33 4 92 03 78 98
Email
lebrun-frenay.c@chu-nice.fr
First Name & Middle Initial & Last Name & Degree
Christine LEBRUN FREANY
Facility Name
Nimes University Hospital
City
Nîmes
ZIP/Postal Code
30900
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Giovanni Castelnovo
Email
giovanni.castelnovo@chu-nimes.fr
First Name & Middle Initial & Last Name & Degree
Giovanni Castelnovo
Facility Name
Rennes University Hospital
City
Rennes
ZIP/Postal Code
35033
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laure Michel
Email
Laure.michel@chu-rennes.fr
First Name & Middle Initial & Last Name & Degree
Laure Michel
Facility Name
Strasbourg University Hospital
City
Strasbourg
ZIP/Postal Code
67000
Country
France
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jerome De Seze
Email
erome.DESEZE@chru-strasbourg.fr
First Name & Middle Initial & Last Name & Degree
Jerome De Seze
12. IPD Sharing Statement
Learn more about this trial
LONG-TERM EFFECTIVENESS AND SAFETY EVALUATION OF OCRELIZUMAB
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