Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From Amyotrophic Lateral Sclerosis (ALS) (MITOTARGET)

This study has been completed.
Sponsor:
Collaborator:
European Commission
Information provided by (Responsible Party):
Trophos
ClinicalTrials.gov Identifier:
NCT00868166
First received: March 23, 2009
Last updated: March 27, 2012
Last verified: March 2012

March 23, 2009
March 27, 2012
April 2009
September 2011   (final data collection date for primary outcome measure)
The primary outcome measure will be the overall 18-month survival rate. [ Time Frame: Survival will be calculated from the date of randomization until the date of death or last follow-up censored at 18 months (548 days). ] [ Designated as safety issue: Yes ]
Same as current
Complete list of historical versions of study NCT00868166 on ClinicalTrials.gov Archive Site
  • Survival without occurrence of tracheostomy, chronic IV or NIV defined as >23h of NIV daily for 14 consecutive days. [ Time Frame: Time to failure will be defined as the time from randomization to the time of the first event to consider (Tracheostomy, IV or NIV) ] [ Designated as safety issue: Yes ]
  • Total score of the 48-point ALS Functional Rating Scale Revised, with a focus on the 9-month assessment [ Time Frame: Inclusion, Month 1, Month 2, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18 ] [ Designated as safety issue: No ]
  • Slow Vital Capacity (SVC) as a percentage of predicted SVC and survival with SVC >50% [ Time Frame: Screening, Inclusion, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18 ] [ Designated as safety issue: Yes ]
  • Total Score of Manual Muscle Testing of 34 muscle groups [ Time Frame: Inclusion, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18 ] [ Designated as safety issue: No ]
  • The single-item Mc Gill Quality of life scale [ Time Frame: Inclusion, Month 1, Month 3, Month 6, Month 9, Month 12, Month 15 and Month 18 ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From Amyotrophic Lateral Sclerosis (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

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.

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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Amyotrophic Lateral Sclerosis
  • Drug: Olesoxime
    2 capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzol 50mg bid
  • Drug: Placebo Comparator
    2 capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid
  • Experimental: TRO19622
    2 Capsules of TRO19622 (330mg) once a day with the noon meal as add-on therapy to riluzole 50mg bid
    Intervention: Drug: Olesoxime
  • Placebo Comparator: Control
    2 Capsules of Placebo once a day with the noon meal as add-on therapy to riluzole 50mg bid
    Intervention: Drug: Placebo Comparator
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
512
September 2011
September 2011   (final data collection date for primary outcome measure)

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).
Both
18 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
Belgium,   France,   Germany,   Spain,   United Kingdom
 
NCT00868166
TRO19622 CL E Q 1015-1, EudraCT Number:2008-007320-25
Yes
Trophos
Trophos
European Commission
Principal Investigator: Vincent Meininger, MD, PhD Groupe Hospitalier Pitie-Salpetriere
Trophos
March 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP