Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From Amyotrophic Lateral Sclerosis (ALS) (MITOTARGET)
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| ClinicalTrials.gov Identifier: NCT00868166 |
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Recruitment Status :
Completed
First Posted : March 24, 2009
Last Update Posted : March 28, 2012
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Amyotrophic Lateral Sclerosis | Drug: Olesoxime Drug: Placebo Comparator | Phase 2 Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 512 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Quadruple (Participant, Care Provider, 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 |
| Study Start Date : | April 2009 |
| Actual Primary Completion Date : | September 2011 |
| Actual Study Completion Date : | September 2011 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: TRO19622
2 Capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid
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Drug: Olesoxime
2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzol 50mg bid |
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Placebo Comparator: Control
2 Capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid
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Drug: Placebo Comparator
2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid |
- 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). ]
- 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) ]
- 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 ]
- 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 ]
- 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 ]
- 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 ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years to 80 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients with sporadic or familial Amyotrophic Lateral Sclerosis
- Patients with a clinical diagnosis of laboratory-supported probable, probable, or definite ALS according to the modified El Escorial criteria8.
- Have signed an Informed Consent to participate to the trial before any study related procedure has taken place.
- Be of age >18 (exclusive) and < 80 years (inclusive).
- If a female, not lactating, has a negative pregnancy test and agrees to use an effective method of birth control.
- Onset of ALS Symptoms (weakness) for more than 6 months (inclusive) and less than 36 months(inclusive).
- Slow vital capacity (SVC), measured three times, one of the measure being >/= 70% of that predicted.
- Treated with riluzole at the stable dose of 50 mg bid for at least 30 days before enrolment.
Exclusion Criteria:
- Tracheostomy, invasive ventilation, or non invasive positive pressure ventilation (NIPPV).
- Gastrostomy.
- Evidence of major psychiatric disorder or clinically evident dementia.
- Diagnosis of a neurodegenerative disease in addition to ALS.
- Have a current medication that could interfere with TRO19622 pharmacokinetics: tamoxifene.
- Have current medications that could interfere with TRO19622 absorption such as ezetimibe, bile salts chelators (cholesteramine), fibrates, phytosterols, niacin (vitamin B3),fish oils. Have a current medication of lipid lowering agents other than statins.
- Known hypersensitivity to any component of the study drug.
- Patients with known intolerance or contra-indication to riluzole.
- Have a recent history (within the previous 6 months) or current evidence of alcohol or drug abuse.
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Have concurrent unstable disease involving any system eg, carcinoma other than basal cell carcinoma, any cardiac dysrhythmia, myocardial infarction, clinical or ECG signs of myocardial ischemia, cardiac insufficiency, angina symptoms, current symptoms of Coronary Artery Disease, or any other condition that in the opinion of the Investigator would make the patient unsuitable for study participation.
. In Germany: Have any cardiac dysrhythmia, myocardial infarction, clinical or ECG signs of myocardial ischemia, cardiac insufficiency, angina symptoms, current symptoms of Coronary Artery Disease or any cardiovascular illness known or identified at the screening or inclusion visits, or have concurrent unstable disease involving any system eg, carcinoma other than basal cell carcinoma or any other condition that in the opinion of the Investigator would make the patient unsuitable for study participation.
- Having a baseline QTc (Bazett) > 450 msec for males and > 470 msec for females.
- Patients with known hepatitis B/C or HIV positive serology.
- Be pregnant female or lactating.
- Have renal impairment defined as blood creatinine > 1:5 X upper limit of normal.
- Have hepatic impairment and/or liver enzymes (ALAT or ASAT) > 3 X ULN.
- Hemostasis disorders or current treatment with oral anticoagulants.
- Be possibly dependent on the Investigator or the Sponsor (eg, including, but not limited to, affiliated employee).
- Participated in any other investigational drug or therapy study with a non approved medication, within the previous 3 months.
- Patients without Social Security Insurance (France).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00868166
| Belgium | |
| University Hospital Gasthuisberg - Dept Neurology - Herestraat 49 | |
| Leuven, Belgium, 3000 | |
| France | |
| 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 | |
| Germany | |
| 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 | |
| Spain | |
| Hospital Carlos III - Unidad de ELA - Sinesio Delgado, 10 | |
| Madrid, Spain, 28029 | |
| United Kingdom | |
| 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 |
| Responsible Party: | Trophos |
| ClinicalTrials.gov Identifier: | NCT00868166 History of Changes |
| Other Study ID Numbers: |
TRO19622 CL E Q 1015-1 EudraCT Number:2008-007320-25 |
| First Posted: | March 24, 2009 Key Record Dates |
| Last Update Posted: | March 28, 2012 |
| Last Verified: | March 2012 |
Keywords provided by Trophos:
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Amyotrophic Lateral Sclerosis TRO19622 Trophos |
Additional relevant MeSH terms:
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Sclerosis Motor Neuron Disease Amyotrophic Lateral Sclerosis Pathologic Processes Neurodegenerative Diseases Nervous System Diseases Neuromuscular Diseases Spinal Cord Diseases Central Nervous System Diseases TDP-43 Proteinopathies Proteostasis Deficiencies |
Metabolic Diseases Riluzole Anticonvulsants Excitatory Amino Acid Antagonists Excitatory Amino Acid Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Neuroprotective Agents Protective Agents |