Adrenoleukodystrophy, Adrenomyeloneuropathy, AMN
Conditions
Keywords
AMN, MD1003, Adrenomyeloneuropathy, ALD, Adrenoleukodystrophy, Biotin, 2MWT, Two-minute walk test, TW25, Timed 25-Foot Walk
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.
Interventions
DRUGMD1003 100 mg capsule
DRUGPlacebo
Sponsors
MedDay Pharmaceuticals SA
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean change of 2 minutes walking test (2MWT) between Months 12 and baseline | Baseline and 12 Months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with improved TW25 (time to walk 25 feet) of at least 20% | Baseline, 9 months, 12 months | at Months 9 and Months 12 compared to the best value among screening and baseline |
| Mean Change in TW25 (time to walk 25 feet) | Baseline and 12 months | — |
| Proportion of patients with improved 2-Minutes-Walk-Tests (2MWT) of at least 20% | Baseline, 9 months, 12 months | at Months 9 and Months 12 compared to the best value among screening and baseline. |
| Euroqol EQ-5D questionnaire | 12 months | Quality of Life questionnaire |
| Qualiveen Questionnaire | 12 Months | Qualiveen to evaluate urinary function |
| Timed up and Go test (TUG) | 12 Months | — |
Countries
France, Germany, Spain
Outcome results
None listed