Effect of MD1003 in Amyotrophic Lateral Sclerosis

This is a 6-month double blind randomized 2:1 placebo-controlled study with two arms (placebo, biotin 300 mg/day). The study will be followed by a 6-month extension phase during which all patients will receive biotin 300 mg/day.


Eligibility Criteria:
Inclusion Criteria:

* Age: 25 to 80 years, inclusive
* Male or female subjects with probable or confirmed ALS (revised international El Escorial criteria, Forbes et al., 2001).
* Patients presenting first motor deficits due to ALS for a maximum of three years at the first consultation in an ALS centre.
* Patients monitored for at least 6 months in an ALS centre or for whom the previous monitoring parameters are available (excepted for MIP and SNIP).
* Patients who have lost at least 5 points on the ALSFRS-R (ALS functional rating scale) during the last 12 months or at least 2 points during the preceding 6 months
* Patients who have been treated with riluzole for at least 3 months at a stable dose. In case of intolerance to this product or refusal for this treatment, patients who have not been treated with riluzole for at least 1 month before inclusion
* For patients with spinal form (onset of the disease affecting limbs) or respiratory form, slow vital capacity \> 60% of predicted value.
* For patients with a bulbar form, slow vital capacity \> 60% of theoretical value or, if spirometry not assessable (severe bulbar disability), patient should not have significant abnormality in both nocturnal capnography and nocturnal oximetry (median pCO2 (carbon dioxide partial pressure ) \< 52 mmHg, SaO2 (arterial oxygen saturation ) \< 90% less than 5% of the time during night) less than 3 months prior inclusion.
* Patients who are willing to give written consent (or oral consent in the presence of a trusted person if the patient is no longer able to write)
* Patients likely to be able to participate in all scheduled evaluation and complete all required study procedures (except for spirometry in bulbar patients with severe disability).

Exclusion Criteria:

* Patients on non-invasive ventilation for respiratory insufficiency due to ALS for more than 10 hours a day
* Patients with an ALSFRS-R score at inclusion of \< 20 (maximum score without disability = 48)
* Patients who have lost less than 5 points on the ALSFRS-R during the last year or less than 2 points during the preceding 6 months
* Patients with a gastrostomy
* Patients who have lost more than 15% of their reference weight (defined as weight before disease onset)
* Patient with dyspnoea at rest or with the least effort (score \< 3 on the dyspnoea item of the ALSFRS-R)
* Patients with dementia
* Patient with severe or rapidly progressive form of ALS for whom the investigator estimates the life expectancy less than 3 months
* Patients with another progressive disease that has not been stabilized at the time of inclusion
* Patients with cancer, except basal cell carcinoma, for less than 5 years, or who require continuous treatment for cancer even if it is older
* Pregnant women.
* Subject who are not covered by a social security scheme.
* Subject under temporary or permanent Judicial Protection.
* Contraception: Both male subjects, and female subjects who are not either surgically sterile (tubal ligation/obstruction or removal of ovaries or uterus) or post-menopausal (no spontaneous menstrual periods for at least one year confirmed by a negative hormone panel), must commit to using two highly effective method of birth control for the duration of the study and for two months after the treatment termination.