MD1003-AMN MD1003 in Adrenomyeloneuropathy

MD1003 in Adrenomyeloneuropathy : a Randomized Double Blind Placebo Controlled Study

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

Study Overview

• Status: Completed
• Conditions: Adrenoleukodystrophy; Adrenomyeloneuropathy; AMN
• Intervention / Treatment: Drug: Placebo; Drug: MD1003 100 mg capsule

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.

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• France
  • Le Kremlin Bicêtre, France, 94275 Cedex
    • Hôpital Bicêtre
  • Paris, France, 75651
    • Groupe Hospitalier Pitie-Salpetriere
• Germany
  • Wermsdorf, Germany, 04779
    • MS-Ambulanz Fachkrankenhaus Hubertusburg
• Spain
  • Barcelona, Spain, 08908
    • Hospital Duran i Reynals / Bellvitge

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 58 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MD1003; MD1003 100mg capsules, 1 capsule tid for 24 months	Drug: MD1003 100 mg capsule; Other Names: High Dose Biotin
Placebo Comparator: Placebo; Placebo capsule, 1 capsule tid for 12 months, then switch to MD1003 100mg capsule, 1 capsule tid for 12 months	Drug: Placebo; Drug: MD1003 100 mg capsule; Other Names: High Dose Biotin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: MedDay Pharmaceuticals SA
• Investigators: Principal Investigator: Patrick Aubourg, MD, Hopital Le Kremlin-Bicêtre; Study Director: Frederic Sedel, MD, Medday Pharmeuticals

Publications and helpful links

Helpful Links

• Sponsor

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: November 9, 2016
• First Submitted That Met QC Criteria: November 10, 2016
• First Posted (Estimate): November 11, 2016

Study Record Updates

• Last Update Posted (Actual): October 9, 2017
• Last Update Submitted That Met QC Criteria: October 6, 2017
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Adrenoleukodystrophy; Biotin; ALD; Adrenomyeloneuropathy; AMN; MD1003; 2MWT; Two-minute walk test; TW25; Timed 25-Foot Walk
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Demyelinating Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Endocrine System Diseases; Genetic Diseases, Inborn; Genetic Diseases, X-Linked; Metabolism, Inborn Errors; Mental Retardation, X-Linked; Intellectual Disability; Heredodegenerative Disorders, Nervous System; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Leukoencephalopathies; Adrenal Gland Diseases; Hereditary Central Nervous System Demyelinating Diseases; Peroxisomal Disorders; Adrenal Insufficiency; Adrenoleukodystrophy; Physiological Effects of Drugs; Micronutrients; Vitamins; Vitamin B Complex; Biotin
• Other Study ID Numbers: MD1003CT2014-01AMN

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No