SERENDEM study: high dose biotin in patients suffering from disability related to peripheral nerve diseases

Phase 1

• Conditions: 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; MedDRA version: 18.1Level: LLTClassification code 10066137Term: Anti-MAG neuropathySystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 18.1Level: PTClassification code 10057645Term: Chronic inflammatory demyelinating polyradiculoneuropathySystem Organ Class: 10029205 - Nervous system disorders; MedDRA version: 18.1Level: LLTClassification code 10008414Term: Charcot-Marie-Tooth diseaseSystem Organ Class: 100000004850; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2015-001150-15-FR
• Lead Sponsor: MEDDAY PHARMACEUTICALS

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-03-02
• Study Completion: 2019-03-18
• Last Update Posted: 19 October 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 15

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 10
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The main objective is to detect a signal of efficacy of high dose biotin in demyelinating polyneuropathies;Secondary Objective: Secondary objective is to asess safety of high dose biotin;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:<br> - motor nerve conduction velocity,<br> - distal latency,<br> - F wave latency,<br> - length of motor nerve potential,<br><br>A 10% improvement for 2 out of these 4 criteria, in at least 3 out of 8 nerves will be considered as clinically meaningful.;Timepoint(s) of evaluation of this end point: Week 12<br>Week 24<br>Week 36<br>Week 48

Secondary Outcome Measures

Name	Time	Method
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.<br>- Clinical endpoints:<br> - ONLS<br> - Timed 10-meter walk test<br> - MRC<br> - INCAT sensory score<br> - 6-minute walk test<br> - Posturometry<br>- Electrophysiological testing endpoints:<br> - Supernormality (%)<br> - Strength-duration time constant (ms)<br> - Rheobase (mA)<br> - Refractoriness (%)<br> - Min-max absolute refractory period (ms);Timepoint(s) of evaluation of this end point: Week 12<br>Week 24<br>Week 36<br>Week 48