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

• Register: EUCTR
• Last refreshed on: 3 April 2012
• Main ID: EUCTR2008-007320-25-DE
• Date of registration: 18/02/2009
• Prospective Registration: Yes
• Primary sponsor: TROPHOS SA
• Public 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
• Scientific 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
• Date of first enrolment: 24/06/2009
• Target sample size: 470
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-007320-25
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: yes Other trial design description: add on of riluzole If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Belgium, France, Germany, Spain, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Patients with sporadic or familial Amyotrophic Lateral Sclerosis
2. Patients with a clinical diagnosis of laboratory-supported probable, probable, or definite ALS according to the modified El Escorial criteria .
3. Have signed an Informed Consent to participate to the trial before any study related procedure has taken place.
4. Be of age >18 and < 80 years.
5. If a female, not lactating, has a negative pregnancy test and agrees to use an effective method of birth control.
6. Onset of ALS Symptoms (weakness) for more than 6 months and less than 36 months.
7. Slow vital capacity (SVC), concordant after 3 measures, =70% of that predicted.
8. Treated with riluzole at the stable dose of 50 mg bid for at least 30 days before enrolment
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Tracheostomy, invasive ventilation, or non invasive positive pressure ventilation (NIPPV).
2. Gastrostomy.
3. Evidence of major psychiatric disorder or clinically evident dementia.
4. Diagnosis of a neurodegenerative disease in addition to ALS.
5. Have a current medication that could interfere with TRO19622 pharmacokinetics: tamoxifene
6. Have current medications that could interfere with TRO19622 absorption such as ezetimibe,bile salts chelators, fibrates, phytosterols, fish oils. Have a current medication of lipid lowering agents other than statins.
7. Known hypersensitivity to any component of the study drug.
8. Patients with known intolerance or contra-indication to riluzole.
9. Have a recent history (within the previous 6 months) or current evidence of alcohol or drug abuse.
10. 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.
11. Having a baseline QTc (Bazett) > 450 msec.
12. Patients with known hepatitis B/C or HIV positive serology.
13. Be pregnant female or lactating.
14. Have renal impairment defined as blood creatinine > 1,5 x upper limit of normal.
15. Have hepatic impairment and/or liver enzymes (ALT or AST) > 3x ULN.
16. Hemostasis disorders or current treatment with oral anticoagulants.
17. Be possibly dependent on the Investigator or the Sponsor (eg, including, but not limited to, affiliated employee).
18. Participated in any other investigational drug or therapy study with a non approved medication, within the previous 3 months.
19. Patients without Social Security Insurance (France).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

ALS is a fatal neuromuscular disorder causing progressive loss of nervous control of voluntary muscles because of destruction of motor neurons in the brain and spinal cord.Riluzole is the only approved drug therapy that has been shown to prolong survival of ALS patients but its efficacy is limited.Consequently, there is a strong medical need to identify other compounds and to evaluate in clinical studies their potential to become a treatment of this devastating disease.
MedDRA version: 9.1 Level: LLT Classification code 10002026 Term: Amyotrophic lateral sclerosis

Intervention(s)

Product Code: TRO19622
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: olesoxime
CAS Number: 2203-87-0
Current Sponsor code: TRO19622
Other descriptive name: 4-cholesten-3-one, oxime
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 165-
Pharmaceutical form of the placebo: Capsule, soft
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): The primary outcome measure will be the overall 18-month survival rate. Survival will be calculated from the date of randomization until the date of death or last follow-up censored at 18 months

Secondary Objective: Evaluation of the safety

Main Objective: Evaluation of 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.

Secondary ID(s)

TRO19622 CL E Q 1015-1