Clinical trial NCT02961803: MD1003-AMN MD1003 in Adrenomyeloneuropathy
Official title: MD1003 in Adrenomyeloneuropathy : a Randomized Double Blind Placebo Controlled Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Adrenomyeloneuropathy
Adrenoleukodystrophy
AMN
Keywords: AMN
MD1003
Adrenomyeloneuropathy
ALD
Adrenoleukodystrophy
Biotin
2MWT
Two-minute walk test
TW25
Timed 25-Foot Walk
Lead sponsor: MedDay Pharmaceuticals SA
Sponsor class: INDUSTRY
First posted: 2016-11-11
Enrollment: 67
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Mean change of 2 minutes walking test (2MWT) between Months 12 and baseline
timeFrame: Baseline and 12 Months
Secondary outcomes:
measure: Proportion of patients with improved 2-Minutes-Walk-Tests (2MWT) of at least 20%
timeFrame: Baseline, 9 months, 12 months
measure: Proportion of patients with improved TW25 (time to walk 25 feet) of at least 20%
timeFrame: Baseline, 9 months, 12 months
measure: Mean Change in TW25 (time to walk 25 feet)
timeFrame: Baseline and 12 months
measure: Timed up and Go test (TUG)
timeFrame: 12 Months
measure: Euroqol EQ-5D questionnaire
timeFrame: 12 months
measure: Qualiveen Questionnaire
timeFrame: 12 Months
Other outcomes:
Locations:
city: Le Kremlin Bicêtre
country: France
facility: Hôpital Bicêtre
city: Paris
country: France
facility: Groupe Hospitalier Pitié-Salpêtrière
city: Wermsdorf
country: Germany
facility: MS-Ambulanz Fachkrankenhaus Hubertusburg
city: Barcelona
country: Spain
facility: Hospital Duran i Reynals / Bellvitge
Study officials:
affiliation: Hopital Le Kremlin-Bicêtre
name: Patrick Aubourg, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Medday Pharmeuticals
name: Frederic Sedel, MD
role: STUDY_DIRECTOR
References: