MD1003-AMN MD1003 in Adrenomyeloneuropathy

Study Overview
=================
Brief Summary
-----------------
The primary objective of the trial is to demonstrate the superiority of biotin at 300 mg/day over placebo in the clinical improvement (walking tests) of patients with adrenomyeloneuropathy

Detailed Description
-----------------
AMN and progressive multiple sclerosis share some similarities including progressive spastic paraparesis and secondary energy failure leading to progressive axonal degeneration. Therefore, it was hypothesized that high doses of biotin might be efficient in patients with AMN.

Official Title
-----------------
MD1003 in Adrenomyeloneuropathy : a Randomized Double Blind Placebo Controlled Study

Conditions
-----------------
Adrenomyeloneuropathy, Adrenoleukodystrophy, AMN

Intervention / Treatment
-----------------
* Drug: MD1003 100 mg capsule
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: ABCD1 gene mutation identified Elevated plasma VLCFA Clinical signs of AMN with at least pyramidal signs in the lower limbs and difficulties to walk EDSS score ≥ 3.5 and ≤ 6.5 Normal brain MRI or brain MRI showing : abnormalities that can be observed in AMN patients without cerebral demyelination with a maximum Loes score of 4 and/or stable (≥6 months) cerebral demyelination without gadolinium enhancement with a Loes score ≤12. Appropriate steroid replacement if adrenal insufficiency is present Likely to be able to participate in all scheduled evaluation visits and complete all required study procedures Signed and dated written informed consent to participate in the study in accordance with local regulations Affiliated to a Health Insurance Exclusion Criteria: Brain MRI abnormalities with a Loes score > 12 or with gadolinium enhancement Any progressive neurological disease other than AMN Impossibility to perform the walk tests and the TUG test Patients with uncontrolled hepatic disorder, renal or cardiovascular disease, or any progressive malignancy Any new medication for AMN including Fampridine initiated less than 1 month prior to inclusion Contra-indications for MRI procedure such as subjects with paramagnetic materials in the body, such as aneurysm clips, pacemakers, intraocular metal or cochlear implants. Inclusion in another therapeutic clinical trial for ALD Not easily contactable by the investigator in case of emergency or not capable to call the investigator

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
Male

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MD1003<br>MD1003 100mg capsules, 1 capsule tid for 24 months | Drug: MD1003 100 mg capsule<br> <br> * Other names: High Dose Biotin;|
| Placebo Comparator: Placebo<br>Placebo capsule, 1 capsule tid for 12 months, then switch to MD1003 100mg capsule, 1 capsule tid for 12 months | Drug: MD1003 100 mg capsule<br> <br> * Other names: High Dose Biotin;Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change of 2 minutes walking test (2MWT) between Months 12 and baseline |  | Baseline and 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with improved 2-Minutes-Walk-Tests (2MWT) of at least 20% | at Months 9 and Months 12 compared to the best value among screening and baseline. | Baseline, 9 months, 12 months | 
| Proportion of patients with improved TW25 (time to walk 25 feet) of at least 20% | at Months 9 and Months 12 compared to the best value among screening and baseline | Baseline, 9 months, 12 months | 
| Mean Change in TW25 (time to walk 25 feet) |  | Baseline and 12 months | 
| Timed up and Go test (TUG) |  | 12 Months | 
| Euroqol EQ-5D questionnaire | Quality of Life questionnaire | 12 months | 
| Qualiveen Questionnaire | Qualiveen to evaluate urinary function | 12 Months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
AMN, MD1003, Adrenomyeloneuropathy, ALD, Adrenoleukodystrophy, Biotin, 2MWT, Two-minute walk test, TW25, Timed 25-Foot Walk