E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Amyotrophic lateral sclerosis |
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E.1.1.1 | Medical condition in easily understood language |
Amyotrophic lateral sclerosis |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002026 |
E.1.2 | Term | Amyotrophic lateral sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Investigation of the safety of biotin in ALS |
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E.2.2 | Secondary objectives of the trial |
Investigation of the effect of biotin on the parameters of clinical progression and on the prognosis of ALS
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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 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. - 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 < 52 mmHg, SaO2 < 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).
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E.4 | Principal 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 ideal weight - 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Safety - Incidence of adverse events - Laboratory testing abnormalities - RBC, WBC, platelets - Ferritin, CPK - Electrolytes, creatinine, glycaemia - AST, ALT, bilirubin, GGT, alkaline phosphatase - Triglyceride, cholesterol - Haemostasis: APPT, PT
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
Efficacy - Motor disability (ALSFRS-R score) - Disease severity - Respiratory parameters - Slow vital capacity (SVC) - Maximal inspiratory pressure (MIP) - Sniff nasal inspiratory pressure (SNIP). - Weight |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |