Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From ALS
Condition: Amyotrophic Lateral Sclerosis
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis
Intervention: Olesoxime; Placebo Comparator; Riluzole
Intervention description: 2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzol 50mg bid; 2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid; Riluzole given as add-on therapy 50mg bid
Intervention MeSH terms: Riluzole
Phase: Phase 3
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 512.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No
Keywords: Amyotrophic Lateral Sclerosis; TRO19622; Trophos

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.
    

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).