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

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

Sponsors

Lead Sponsor: Hoffmann-La Roche

Collaborator: European Commission

Source Hoffmann-La Roche
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.

Overall Status Completed
Start Date April 30, 2009
Completion Date September 30, 2011
Primary Completion Date September 30, 2011
Phase Phase 3
Study Type Interventional
Primary Outcome
Measure Time Frame
Overall Survival Rate at 18 Months From the date of randomization until the date of death or last follow-up censored at 18 months (548 days)
Secondary Outcome
Measure Time Frame
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)
Global Score of Manual Muscle Testing (MMT) of 34 Muscle Groups Inclusion, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18
The Single-Item Mc Gill Quality of Life Scale Inclusion, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18
Enrollment 512
Condition
Intervention

Intervention Type: Drug

Intervention Name: Olesoxime

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

Arm Group Label: Olesoxime

Other Name: TRO19622

Intervention Type: Drug

Intervention Name: Placebo Comparator

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

Arm Group Label: Placebo Comparator

Other Name: Placebo

Intervention Type: Drug

Intervention Name: Riluzole

Description: Riluzole given as add-on therapy 50mg bid

Other Name: 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).

Gender: All

Minimum Age: 18 Years

Maximum Age: 80 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Clinical Trials Study Director Hoffmann-La Roche
Location
Facility:
University Hospital Gasthuisberg - Dept Neurology - Herestraat 49 | Leuven, 3000, Belgium
HCL Hôpital Neurologique et Neurochirurgical Pierre Wertheimer - Neurologie C et Laboratoire d'électromyographie - 59, boulevard Pinel | Bron Cedex, 69677, France
CHRU de LILLE - Hôpital Roger Salengro - Centre SLA-MMN - Sce de Neurologie et Pathologie du Mouvement | Lille, 59037, France
Centre SLA Limoges - Service de Neurologie | Limoges, 87042, France
Hôpital La Timone - Service Neurologie et Maladies Neuromusculaires | Marseille, 13005, France
Clinique du Motoneurone - Sce d'Explorations Neurologiques - Hôpital Gui de Chauliac | Montpellier, 34295, France
CHU de Nice - Hôpital de l'Archet 1 - Centre de Référence pour les Maladies Neuromusculaires et la SLA | Nice, 06202, France
Groupe Hospitalier PITIE-SALPETRIERE - Fédération des Maladies du Système Nerveux | Paris, 75013, France
Charité Universitätsmedizin Berlin, Campus Virchow-Klinikum, Neurologische Poliklinik Ambulanz für ALS und andere Motoeneuronenerkrankungen | Berlin, 13353, Germany
Universitätsklinik und Poliklinik für Neurologie - Martin-Luther-Universität Halle-Wittenberg | Halle, 06097, Germany
Neurologische Klinik Medizinische Hochschule | Hannover, D-30623, Germany
Universitäts- und Rehabilitationskliniken Ulm (RKU) - Neurologische Universitätsklinik | Ulm, 89081, Germany
Hospital Carlos III - Unidad de ELA - Sinesio Delgado, 10 | Madrid, 28029, Spain
King's MND Care and Research Center - Academic Neurosciences Building PO Box 41 Institute of Psychiatry | London, SE58AF, United Kingdom
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 Countries

Belgium

France

Germany

Spain

United Kingdom

Verification Date

February 2020

Responsible Party

Type: Sponsor

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Olesoxime

Type: Experimental

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

Label: Placebo Comparator

Type: Placebo Comparator

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

Acronym MITOTARGET
Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Other

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov