E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
chronic inflammatory demyelinating polyradiculoneuropathy, demyelinating neuropathy associated with immunoglobulin M (IgM) monoclonal gammopathy and antibodies against myelin-associated glycoprotein (MAG), Charcot Marie Tooth Ia (CMT Ia) neuropathy |
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E.1.1.1 | Medical condition in easily understood language |
Various causes of walking disabilty related to peripheral nerve diseases such as CIDP, MAG and CMT1 |
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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 | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10066137 |
E.1.2 | Term | Anti-MAG neuropathy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10057645 |
E.1.2 | Term | Chronic inflammatory demyelinating polyradiculoneuropathy |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10008414 |
E.1.2 | Term | Charcot-Marie-Tooth disease |
E.1.2 | System Organ Class | 100000004850 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The main objective is to detect a signal of efficacy of high dose biotin in demyelinating polyneuropathies |
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E.2.2 | Secondary objectives of the trial |
Secondary objective is to asess safety of high dose biotin |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male and female aged between 20 and 85 years. - Patients fulfilling one of the following diagnosis: - Five patients with chronic inflammatory demyelinating polyneuropathy on both clinical and neurophysiological grounds. - Five patients with proven genetic diagnosis of CMT1a - Five patients with anti-MAG polyneuropathy. - Electrophysiological parameters worsening for the past 3 years - Available EMG record, performed during the past 6 months to assess variability of NCV parameters - Signed and dated written informed consent to participate in the study in accordance with local regulations - Likely to be able to participate in all scheduled evaluation and complete all required study procedures, - In the opinion of the investigator, the patient will be compliant and have a high probability of completing the study. |
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E.4 | Principal exclusion criteria |
- Any general chronic handicapping disease other than peripheral neuropathy - Impossibility to perform the 10 meters walking test - Impossibility to assess electrophysiological parameters - Patients with uncontrolled hepatic disorder, renal or cardiovascular disease, or cancer, - Patients with hypersensitivity to MD1003 excipients (lactose) - Laboratory tests out of normal range according to the reference laboratory values. Deviations may be accepted if considered by the investigator as not clinically significant with regards to the study continuation, - Patients with history or presence of alcohol abuse or drug addiction, - Patients likely to be non-compliant to the study procedures or for whom a long-term follow-up seems to be difficult to achieve. - Any new medication for neuropathy initiated less than 3 months prior to inclusion. - For CIDP patients, relapse in the past 3 months before inclusion - Not easily contactable by the investigator in case of emergency or not capable to call the investigator - Pregnant woman or of childbearing potential without effective contraception |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint is the change between baseline and end of the study of each following electrophysiological criteria of demyelination measured on 8 nerves: - motor nerve conduction velocity, - distal latency, - F wave latency, - length of motor nerve potential,
A 10% improvement for 2 out of these 4 criteria, in at least 3 out of 8 nerves will be considered as clinically meaningful. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Week 12 Week 24 Week 36 Week 48 |
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E.5.2 | Secondary end point(s) |
Secondary endpoints will be part of exploratory analyses. They will consist in studying mean change or proportions for the following clinical and electrophysiological parameters. - Clinical endpoints: - ONLS - Timed 10-meter walk test - MRC - INCAT sensory score - 6-minute walk test - Posturometry - Electrophysiological testing endpoints: - Supernormality (%) - Strength-duration time constant (ms) - Rheobase (mA) - Refractoriness (%) - Min-max absolute refractory period (ms) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Week 12 Week 24 Week 36 Week 48 |
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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 | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
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 | |