Effect of MD1003 in Amyotrophic Lateral Sclerosis: a Randomized Double Blind Placebo Controlled Pilot Study
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Recording of adverse events
Study Overview
Brief Summary
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Other
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 25 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
PLACEBO
This formulation consists in lactose powder and other excipients (magnesium stearate, croscarmellose sodium, Silica) as placebo, tid during 6 months and then switch to MD1003 tid during 6 additional months.
Intervention: Placebo oral capsule (Drug)
MD1003
The investigational drug will consist in capsules of 100 mg biotin and excipients (lactose, magnesium stearate, croscarmellose sodium, Silica) tid during 12 months
Intervention: MD1003 (Drug)
PLACEBO
This formulation consists in lactose powder and other excipients (magnesium stearate, croscarmellose sodium, Silica) as placebo, tid during 6 months and then switch to MD1003 tid during 6 additional months.
Intervention: MD1003 (Drug)
Outcomes
Primary Outcomes
Recording of adverse events
Time Frame: 6 months
All adverse events in two groups will be recorded.
Laboratory testing (haematology and biochemistry panel)
Time Frame: 6 months
* RBC (red blood cell), WBC (white blood cell ), platelets * Ferritin, CPK (creatine phosphokinase ) * Electrolytes, creatinine, glycaemia * AST (aspartate aminotransferase ), ALT (alanine aminotransferase) , bilirubin, GGT (gamma-glutamyltransferase), alkaline phosphatase * Triglyceride, cholesterol * Haemostasis: APPT (activated partial thromboplastin time), PT (prothrombin time )
Secondary Outcomes
- Slow vital capacity (SVC)(6 months)
- Maximal inspiratory pressure (MIP)(6 months)
- Motor disability(6 months)
- Severity(6 months)
- Sniff nasal inspiratory pressure (SNIP)(6 months)
- Weight(6 months)