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

NCT00868166 | Completed Phase 3 Results DMC

• 3 other identifiers: WN29853EudraCT Number:2008-007320-25TRO19622 CL E Q 1015-1
• Study Type: interventional
• Target: 512
• Locations: 5 countries
• Sites: 15

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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Amyotrophic Lateral Sclerosis; TRO19622; Trophos

Outcome Measures

Primary Outcomes (1)

• Overall Survival Rate at 18 Months

  Overall survival was defined from the date of randomization until the date of death (event) or last known alive date (censored). If the death date was after 18 months, the participant was censored at 18 months (548 days). Participants still alive at or after 18 months were censored at 18 months/ 548 days. All data over the 18-month follow-up period after randomization, and participant survival status at the 18-month follow-up visit for participants who withdrew prematurely from the study for reasons other than death were included.

  From the date of randomization until the date of death or last follow-up censored at 18 months (548 days)

Secondary Outcomes (7)

• Percentage of Participants With Failure Over 18 Months

  From randomization to the time of the first event to consider at 18 months (548 days)

• Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised (ALSFRS-R)

  Inclusion, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18

• Percentage of Participants With a Global ALS FRS-R Score of <30 or Death

  Month 18 (548 days)

• Slow Vital Capacity (SVC) Percent Predicted

  Baseline, Inclusion, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18

• Percentage of Participants With SVC Percent Predicted <70% or Had Died Over 18 Months

  Month 18 (548 days)

Study Arms (2)

Olesoxime

EXPERIMENTAL

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

Drug: Olesoxime; Drug: Riluzole

Placebo Comparator

PLACEBO COMPARATOR

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

Drug: Placebo Comparator; Drug: Riluzole

Interventions

Olesoxime DRUG

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

Also known as: TRO19622

Olesoxime

Placebo Comparator DRUG

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

Also known as: Placebo

Placebo Comparator

Riluzole DRUG

Riluzole given as add-on therapy 50mg bid

Also known as: Rilutek

Olesoxime; Placebo Comparator

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Hoffmann-La Roche: lead
• European Commission: collaborator

Study Sites (15)

University Hospital Gasthuisberg - Dept Neurology - Herestraat 49

Leuven, 3000, Belgium

Location

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

Bron, 69677, France

Location

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

Lille, 59037, France

Location

Centre SLA Limoges - Service de Neurologie

Limoges, 87042, France

Location

Hôpital La Timone - Service Neurologie et Maladies Neuromusculaires

Marseille, 13005, France

Location

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

Montpellier, 34295, France

Location

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

Nice, 06202, France

Location

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

Paris, 75013, France

Location

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

Berlin, 13353, Germany

Location

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

Halle, 06097, Germany

Location

Neurologische Klinik Medizinische Hochschule

Hanover, D-30623, Germany

Location

Universitäts- und Rehabilitationskliniken Ulm (RKU) - Neurologische Universitätsklinik

Ulm, 89081, Germany

Location

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

Madrid, 28029, Spain

Location

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

London, SE58AF, United Kingdom

Location

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

Sheffield, S10 2RX, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 34433481 DERIVED

• 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.

  PMID: 30814647 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

olesoxime; Riluzole

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Benzothiazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 23, 2009
• First Posted: March 24, 2009
• Study Start: April 30, 2009
• Primary Completion: September 30, 2011
• Study Completion: September 30, 2011
• Last Updated: February 25, 2020
• Results First Posted: February 15, 2019

Record last verified: 2020-02

Locations

FR (7); BE (1); DE (4); ES (1); GB (2)