Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From Amyotrophic Lateral Sclerosis (ALS) (MITOTARGET)
The purpose of the assay is to assess the safety and the efficacy of TRO19622 330 mg QD as add-on therapy to riluzole 50 mg bid in the treatment of patients suffering from ALS, as compared to placebo, assessed by the 18-month survival rate.
Amyotrophic Lateral Sclerosis
Drug: Placebo Comparator
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
|Official Title:||Phase II/III, Multicenter, Randomized, Parallel Group, Double-blind, Placebo Controlled Study to Assess Safety and Efficacy of TRO19622 in Amyotrophic Lateral Sclerosis (ALS) Patients Treated With Riluzole|
- The primary outcome measure will be the overall 18-month survival rate. [ Time Frame: Survival will be calculated from the date of randomization until the date of death or last follow-up censored at 18 months (548 days). ] [ Designated as safety issue: Yes ]
- Survival without occurrence of tracheostomy, chronic IV or NIV defined as >23h of NIV daily for 14 consecutive days. [ Time Frame: Time to failure will be defined as the time from randomization to the time of the first event to consider (Tracheostomy, IV or NIV) ] [ Designated as safety issue: Yes ]
- Total score of the 48-point ALS Functional Rating Scale Revised, with a focus on the 9-month assessment [ Time Frame: Inclusion, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18 ] [ Designated as safety issue: No ]
- Slow Vital Capacity (SVC) as a percentage of predicted SVC and survival with SVC >50% [ Time Frame: Screening, Inclusion, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18 ] [ Designated as safety issue: Yes ]
- Total Score of Manual Muscle Testing of 34 muscle groups [ Time Frame: Inclusion, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18 ] [ Designated as safety issue: No ]
- The single-item Mc Gill Quality of life scale [ Time Frame: Inclusion, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18 ] [ Designated as safety issue: No ]
|Study Start Date:||April 2009|
|Study Completion Date:||September 2011|
|Primary Completion Date:||September 2011 (Final data collection date for primary outcome measure)|
2 Capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid
2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzol 50mg bid
Placebo Comparator: Control
2 Capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid
Drug: Placebo Comparator
2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid
A stand alone treatment with TRO19622 is not acceptable for ethical reasons. Riluzole is an approved and widely used ALS treatment in the European community, in Japan and in the USA.
Therefore, in this study, TRO19622 will be assessed as add-on to riluzole in patients suffering from ALS.
At the start of the study, patients will be randomized to one of two groups : TRO19622 (330 mg QD or placebo (once a day).
Each treatment will be administered for 18 months under double-blind conditions. The product under evaluation will be administered to patients receiving the standard of care for ALS, including riluzole.
Riluzole dosage (50 mg bid) must be stable and well tolerated for at least one month prior to inclusion into the study.
After the double-blind period, open-label administration of TRO19622 will be allowed for safety and survival assessments and until efficacy results are available.
A separate open-label protocol will be written 6 months after the randomization of the last patient into the study.
|University Hospital Gasthuisberg - Dept Neurology - Herestraat 49|
|Leuven, Belgium, 3000|
|HCL Hôpital Neurologique et Neurochirurgical Pierre Wertheimer - Neurologie C et Laboratoire d'électromyographie - 59, boulevard Pinel|
|Bron Cedex, France, 69677|
|CHRU de LILLE - Hôpital Roger Salengro - Centre SLA-MMN - Sce de Neurologie et Pathologie du Mouvement|
|Lille, France, 59037|
|Centre SLA Limoges - Service de Neurologie|
|Limoges, France, 87042|
|Hôpital La Timone - Service Neurologie et Maladies Neuromusculaires|
|Marseille, France, 13005|
|Clinique du Motoneurone - Sce d'Explorations Neurologiques - Hôpital Gui de Chauliac|
|Montpellier, France, 34295|
|CHU de Nice - Hôpital de l'Archet 1 - Centre de Référence pour les Maladies Neuromusculaires et la SLA|
|Nice, France, 06202|
|Groupe Hospitalier PITIE-SALPETRIERE - Fédération des Maladies du Système Nerveux|
|Paris, France, 75013|
|Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Neurologische Poliklinik Ambulanz für ALS und andere Motoeneuronenerkrankungen|
|Berlin, Germany, 13353|
|Universitätsklinik und Poliklinik für Neurologie - Martin-Luther-Universität Halle-Wittenberg|
|Halle, Germany, 06097|
|Neurologische Klinik Medizinische Hochschule|
|Hannover, Germany, D-30623|
|Universitäts- und Rehabilitationskliniken Ulm (RKU) - Neurologische Universitätsklinik|
|Ulm, Germany, 89081|
|Hospital Carlos III - Unidad de ELA - Sinesio Delgado, 10|
|Madrid, Spain, 28029|
|King's MND Care and Research Center - Academic Neurosciences Building PO Box 41 Institute of Psychiatry|
|London, United Kingdom, SE58AF|
|Academic Neurology Unit - University of Sheffield - Section of Neuroscience - Division of Genomic Medicine - School of Medicine and Biomedical Sciences|
|Sheffield, United Kingdom, S10 2RX|
|Principal Investigator:||Vincent Meininger, MD, PhD||Groupe Hospitalier Pitie-Salpetriere|