Multiple SclerosisPhase 3CONSONANCE EXNCT05210621
LONG-TERM EFFECTIVENESS AND SAFETY EVALUATION OF OCRELIZUMAB
A Phase 3 study testing Ocrelizumab in people with Multiple Sclerosis, run by Centre Hospitalier Universitaire de Nice at 15 sites in France.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Ocrelizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 15 sitesFrance
- Study dates
- 8 Mar 2022to 24 Feb 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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)
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
France15 sites
Amiens University Hospital
Amiens, 80051
Bayonne Hospital
Bayonne, 64100
Bordeaux University Hospital
Bordeaux, 33076
Caen University Hospital
Caen, 14033
Clermont ferrand University Hospital
Clermont-Ferrand, 63003
Lille University Hospital
Lille, 59037
Lyon University Hospital
Lyon, 69677
Marseille Univesity Hospital
Marseille, 13385
Montpellier University Hospital
Montpellier, 34295
Nancy University Hospital
Nancy, 54000
Nantes University hospital
Nantes, 42055
Nice University Hospital
Nice, 06000
Nimes University Hospital
Nîmes, 30900
Rennes University Hospital
Rennes, 35033
Strasbourg University Hospital
Strasbourg, 67000
About this study
Official title: LONG-TERM EFFECTIVENESS AND SAFETY EVALUATION OF OCRELIZUMAB IN FRENCH PATIENTS WITH PROGRESSIVE MS: CONSONANCE EXTENSION STUDY
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.
Read more
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).
- 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
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
| Study group | Role | What they receive |
|---|---|---|
| Patients with MS who have completed the CONSONANCE study | Other | Not described Receives: Drug: Ocrelizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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,
Measured: baseline
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,
Measured: week 192.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2022
- Study start8 Mar 2022
- Primary completion24 Feb 2026 (estimated)
- Study completion24 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de NiceThe 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.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Nice
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05210621
- Sponsor's protocol ID
- 21-PP-23
- Acronym
- CONSONANCE EX
- Status last verified
- May 2024
- First submitted
- 14 Jan 2022
- Last updated
- 17 May 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- LONG-TERM EFFECTIVENESS AND SAFETY EVALUATION OF OCRELIZUMAB IN FRENCH PATIENTS WITH PROGRESSIVE MS: CONSONANCE EXTENSION STUDY
- ClinicalTrials.gov ID
- NCT05210621
- Acronym / sponsor ID
- CONSONANCE EX / 21-PP-23
- Conditions
- Multiple Sclerosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de NiceUniversity, hospital or other
- Study start
- 8 Mar 2022 (actual)
- Primary completion
- 24 Feb 2026 (estimated)
- Study completion
- 24 Feb 2029 (estimated)
- First posted
- 27 Jan 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with MS who have completed the CONSONANCE study | Other | Drug: Ocrelizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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)
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ocrelizumabocrelizumab 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 | Drug | Patients with MS who have completed the CONSONANCE study |
Primary outcome
Proportion of patients with upper limb disability progression
Time frame: baseline
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
Time frame: week 192.
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,
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 May 2024.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ocrelizumab in people with Multiple Sclerosis, run by Centre Hospitalier Universitaire de Nice at 15 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 17 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with upper limb disability progression (time frame: baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 May 2024.