Multiple Sclerosis Clinical Trial
— STOP-I-SEPOfficial title:
Disease Modifying Therapies Withdrawal in Inactive Secondary Progressive Multiple Sclerosis Patients Older Than 50 Years
Further controlled and randomized prospective studies in Multiple sclerosis, analyzing the potential impact of treatment discontinuation on disability progression, focal disease activity and quality of life are needed. The optimum patient age and duration of inactive SPMS before treatment withdrawal and the monitoring procedures also need to be specified, the ultimate goal being to provide evidence-based recommendations for clinical practice. Following the previous retrospective experience, we decided to drive a multicenter prospective study in France based on the hypothesis that stopping disease modifying therapy will not induce an increased risk of disability progression and relapse in selected SPMS patients (older patients without lesion activity) but will improve the quality of life and may reduce treatment-related costs.
Status | Recruiting |
Enrollment | 250 |
Est. completion date | January 2028 |
Est. primary completion date | July 2026 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 50 Years and older |
Eligibility | Inclusion Criteria: - Patients > 50 years old; - Secondary progressive phenotype for at least 3 years; The secondary progressive phenotype will be defined as progressive deterioration of disability not due to relapse, with an increase of at least 1 EDSS point since the beginning of the progressive phase (or 0.5 EDSS point if EDSS score = 5.5). - Disease modifying therapy of MS for at least 3 years (interferon, glatiramer acetate, teriflunomide, dimethyl fumarate, cyclophosphamide, azathioprine, methotrexate, mycophenolate mofetil, rituximab, ocrelizumab); Both patients with the same DMT or with successive DMTs during 3 years can be included. It is important to note that patients could have been treated with fingolimod or natalizumab 2 or 3 years before inclusion, but not during the year before inclusion ; - No evidence of focal inflammatory activity for at least 3 years (no clinical relapse and no gadolinium enhancement on an MRI scan); - EDSS=3. Concomitant medications with Fampridine are allowed throughout the study, provided they have been introduced at least 1 months before inclusion. Natalizumab and fingolimod during the year before inclusion were excluded because of the risk of recurrence of inflammatory activity or even rebound of inflammatory activity after withdrawal. Both patients with the same DMT or with successive DMTs during 3 years can be included, as for example, cyclophosphamide is used for 1 or 2 years, sometimes followed by mycophenolate mofetil. For Rituximab and Ocrelizumab, inclusion in STOP-I-SEP will be at 6 months from the last infusion to take into account the mode of action of these treatments and their specific administration scheme. Exclusion Criteria: - Patients treated with mitoxantrone or alemtuzumab, during the previous 3 years before inclusion; - Patients treated with natalizumab or fingolimod during the year before inclusion; - Change of disease modifying therapy of MS for less than a year - Other neurological or systemic disease ; - Incapacity to understand or sign the consent form ; - Contraindication to MRI ; - Pregnancy or breast-feeding ; - Patient in another clinical trial - Persons referred to in Articles L. 1121-5 to L. 1121-8 and L. 1122-1-2 of the Public Health Code (eg minors, protected adults, …). |
Country | Name | City | State |
---|---|---|---|
France | CHU Angers | Angers | |
France | CHU de Bordeaux | Bordeaux | |
France | CHU Brest | Brest | |
France | CH de Chartres | Chartres | |
France | CHU Clermont-Ferrand | Clermont-Ferrand | |
France | Hôpital Henri Mondor | Créteil | |
France | CHU Dijon | Dijon | |
France | CHU Grenoble | Grenoble | |
France | CH de Libourne | Libourne | |
France | CHU Lille | Lille | |
France | Hôpital Saint Vincent de Paul | Lille | |
France | Hospices Civils Lyon | Lyon | |
France | AP-HM | Marseille | |
France | CHU Montpellier | Montpellier | |
France | CHU Nancy | Nancy | |
France | CHU Nantes | Nantes | |
France | CHU Nice | Nice | |
France | CHU de Nîmes | Nîmes | |
France | AP-HP (La Pitié Salpêtrière) | Paris | |
France | Fondation de Rothschild | Paris | |
France | CH Poissy | Poissy | |
France | CHU Poitiers | Poitiers | |
France | CH Quimper | Quimper | |
France | CHU Rennes | Rennes | |
France | CHU Strasbourg | Strasbourg | |
France | CH de Foch | Suresnes | |
France | CHU Tours | Tours |
Lead Sponsor | Collaborator |
---|---|
Rennes University Hospital |
France,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Disability progression measured by EDSS | Disability progression measured by the Percentage of patients experiencing disability progression (confirmed at 6 months) at 2 years. Disability progression will be defined as an increase in the EDSS of at least 1 point if the baseline EDSS was 5.5 or less, or 0.5 point if the Baseline EDSS was more than 5.5. |
24 months | |
Secondary | Time of Disability progression | Disability progression measured by Time from DMT withdrawal to disability progression | 24 months | |
Secondary | Disability progression measured by composite score | Disability progression measured by Change in a composite disability progression score (increase in the EDSS score, or an increase in the time to perform the timed 25-foot walk = 20%, or an increase in the time to complete the 9-hole peg test = 20%) confirmed at 6 months | 24 months | |
Secondary | Disability progression measured by SDMT | Disability progression measured by Change in the SDMT score from baseline to 2-year | 24 months | |
Secondary | Percentage of patients with Relapse | Relapses measured by Percentage of patients with at least one relapse from baseline to 2-year | 24 months | |
Secondary | Annualized relapse rate | Relapses measured by Annualized relapse rate during 2-year | 24 months | |
Secondary | Time of Relapses | Relapses measured byTime from DMT withdrawal to first relapse; | 24 months | |
Secondary | Percentage of patients with brain lesion | Percentage of patients with one or more new or enlarging brain MRI (Magnetic Resonance Imaging) lesions from baseline to 2-year | 24 months | |
Secondary | Percentage of patients with gadolinium enhancing lesion | Percentage of patients with at least one gadolinium enhancing lesion(s) at 6 months, and/or 1 year,and/or 2-year | 24 months | |
Secondary | Change in brain volume | Change in brain volume from baseline to 2-year measured on MRI | 24 months | |
Secondary | Percentage of patients with no evidence of disease activity | Percentage of patients with no evidence of disease activity (NEDA 3: no clinical relapse, no MRI activity, no disability progression) at 2-year | 24 months | |
Secondary | Percentage of patients who resume DMT in the treatment withdrawal group | Percentage of patients who resume DMT in the treatment withdrawal group at 2-year | 24 months | |
Secondary | Quality of life measured by SEP-59 score | Change in the SEP-59 score from baseline to 2-year; | 24 months | |
Secondary | Quality of life measured by EQ-5D score | Change in the EuroQOL EQ-5D from baseline to 2-year; | 24 months | |
Secondary | Medico economic impact | Incremental Cost Effectiveness Ratio (ICER) defined as the cost for QALY gained in "treatment withdrawal group" versus "treatment continued group" | 24 months |
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