Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS

NCT ID: NCT00868166

Last Updated: 2020-02-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 512 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-30
• Study Completion Date: 2011-09-30

Brief Summary

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.

Detailed Description

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.

Conditions

Amyotrophic Lateral Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

Olesoxime

2 Capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid

Group Type: EXPERIMENTAL

Olesoxime

Intervention Type: DRUG

2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzol 50mg bid

Riluzole

Intervention Type: DRUG

Riluzole given as add-on therapy 50mg bid

Placebo Comparator

2 Capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid

Group Type: PLACEBO_COMPARATOR

Placebo Comparator

Intervention Type: DRUG

2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid

Riluzole

Intervention Type: DRUG

Riluzole given as add-on therapy 50mg bid

Interventions

Olesoxime

2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzol 50mg bid

Intervention Type: DRUG

Placebo Comparator

2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid

Intervention Type: DRUG

Riluzole

Riluzole given as add-on therapy 50mg bid

Intervention Type: DRUG

Other Intervention Names

TRO19622; Placebo; Rilutek

Eligibility Criteria

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.
• 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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Commission

OTHER

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

University Hospital Gasthuisberg - Dept Neurology - Herestraat 49

Leuven, , Belgium

HCL Hôpital Neurologique et Neurochirurgical Pierre Wertheimer - Neurologie C et Laboratoire d'électromyographie - 59, boulevard Pinel

Bron, , France

CHRU de LILLE - Hôpital Roger Salengro - Centre SLA-MMN - Sce de Neurologie et Pathologie du Mouvement

Lille, , France

Centre SLA Limoges - Service de Neurologie

Limoges, , France

Hôpital La Timone - Service Neurologie et Maladies Neuromusculaires

Marseille, , France

Clinique du Motoneurone - Sce d'Explorations Neurologiques - Hôpital Gui de Chauliac

Montpellier, , France

CHU de Nice - Hôpital de l'Archet 1 - Centre de Référence pour les Maladies Neuromusculaires et la SLA

Nice, , France

Groupe Hospitalier PITIE-SALPETRIERE - Fédération des Maladies du Système Nerveux

Paris, , France

Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Neurologische Poliklinik Ambulanz für ALS und andere Motoeneuronenerkrankungen

Berlin, , Germany

Universitätsklinik und Poliklinik für Neurologie - Martin-Luther-Universität Halle-Wittenberg

Halle, , Germany

Neurologische Klinik Medizinische Hochschule

Hanover, , Germany

Universitäts- und Rehabilitationskliniken Ulm (RKU) - Neurologische Universitätsklinik

Ulm, , Germany

Hospital Carlos III - Unidad de ELA - Sinesio Delgado, 10

Madrid, , Spain

King's MND Care and Research Center - Academic Neurosciences Building PO Box 41 Institute of Psychiatry

London, , United Kingdom

Academic Neurology Unit - University of Sheffield - Section of Neuroscience - Division of Genomic Medicine - School of Medicine and Biomedical Sciences

Sheffield, , United Kingdom

Countries

Belgium; France; Germany; Spain; United Kingdom

References

Witzel S, Frauhammer F, Steinacker P, Devos D, Pradat PF, Meininger V, Halbgebauer S, Oeckl P, Schuster J, Anders S, Dorst J, Otto M, Ludolph AC. Neurofilament light and heterogeneity of disease progression in amyotrophic lateral sclerosis: development and validation of a prediction model to improve interventional trials. Transl Neurodegener. 2021 Aug 26;10(1):31. doi: 10.1186/s40035-021-00257-y.

Reference Type: DERIVED

PMID: 34433481 (View on PubMed)

Devos D, Moreau C, Kyheng M, Garcon G, Rolland AS, Blasco H, Gele P, Timothee Lenglet T, Veyrat-Durebex C, Corcia P, Dutheil M, Bede P, Jeromin A, Oeckl P, Otto M, Meininger V, Danel-Brunaud V, Devedjian JC, Duce JA, Pradat PF. A ferroptosis-based panel of prognostic biomarkers for Amyotrophic Lateral Sclerosis. Sci Rep. 2019 Feb 27;9(1):2918. doi: 10.1038/s41598-019-39739-5.

Reference Type: DERIVED

PMID: 30814647 (View on PubMed)

Other Identifiers

EudraCT Number:2008-007320-25

Identifier Type: -

Identifier Source: secondary_id

TRO19622 CL E Q 1015-1

Identifier Type: OTHER

Identifier Source: secondary_id

WN29853

Identifier Type: -

Identifier Source: org_study_id