Study to evaluate effect of MIN-102 compared to Placebo after 96 weeks of randomized, double-blind Treatment followed by open-label extension study to evaluate effect of long term treatment with MIN-102 on the progression of adrenomyeloneuropathy (AMN) in male patients

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2017-000748-16-HU
• Date of registration: 30/06/2017
• Prospective Registration: Yes
• Primary sponsor: Minoryx Therapeutics S.L.
• Public title: Study to evaluate effect of MIN-102 compared to Placebo after 96 weeks of randomized, double-blind Treatment followed by open-label extension study to evaluate effect of long term treatment with MIN-102 on the progression of adrenomyeloneuropathy (AMN) in male patients
• Scientific title: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTINATIONAL, MULTICENTER STUDY WITH OPEN-LABEL TREATMENT EXTENSION TO ASSESS THE EFFECT OF MIN-102 ON THE PROGRESSION OF ADRENOMYELONEUROPATHY IN MALE PATIENTS WITH X-LINKED ADRENOLEUKODYSTROPHY - ADVANCE
• Date of first enrolment: 04/09/2017
• Target sample size: 105
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-000748-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: yes Other trial design description: Main Study is Randomized, Controlled, Double-Blind and Extension Study is Open-Label If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Hungary, Italy, Netherlands, Spain, United Kingdom, United States

Contacts

• Name: Sílvia Pascual
• Affiliation: Minoryx Therapeutics S.L.

• Name: Sílvia Pascual
• Affiliation: Minoryx Therapeutics S.L.

Key inclusion & exclusion criteria

Inclusion criteria:
Main Study:
1. Male patients aged =18 to =65 years.
2. Diagnosis of ALD based on elevated very long-chain fatty acids (VLCFA) and genetic testing
3. Clinical evidence of spinal cord involvement, with an EDSS score between 2 and 6
4. Ability to walk for 6 minutes, without or with rest, with usual walking aids (cane or walker)
5. Ability to stand on a force plate with closed eyes and with feet apart for a minimum of 20 seconds
6. Either a normal brain MRI or a type-3 pattern MRI abnormality in which the abnormality is considered to represent the centripetal extension of the distal axonopathy
7. Normal adrenal function or appropriate steroid replacement if adrenal insufficiency is present.

Extension Study:
1. Consent to participate in the extension study part
2. Completion of the entire 96-weeks double-blind period of the study (Part 1) and consent to participate in the extension study part
3. Normal adrenal function or appropriate steroid replacement
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 105
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Main Study & Extension Study:
1. Any other chronic neurological disease with signs of spastic paraplegia
2. Known type 1 or type 2 diabetes.
3. Known intolerance to pioglitazone or any other thiazolidinedione.
4. Previous or current use of honokiol, pioglitazone or other thiazolidinediones, biotin (MD-1003), unstable dose of Lorenzo's oil
5. Current treatment with immunosuppressant medication, except for corticosteroids.
6. Previous or current history of cancer, bone marrow transplantation, Congestive heart failure, significant liver and renal disorders, anemia, pulmonary or cardiac diseases, Cognitive or behavioral abnormalities, alcohol/drug abuse etc.









Age minimum:
Age maximum:
Gender:
Female: no
Male: yes

Health Condition(s) or Problem(s) studied

ADRENOMYELONEUROPATHY IN MALE PATIENTS WITH X-LINKED ADRENOLEUKODYSTROPHY

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: 5-[4-[2-(5-(1-hydroxyethyl)-2-pyridinyl)ethoxy]benzyl]-2,4-thiazolidinedione hydrochloride
Product Code: MIN-102
Pharmaceutical Form: Oral suspension
INN or Proposed INN: 5-[4-[2-(5-(1-hydroxyethyl)-2-pyridinyl)ethoxy]benzyl]-2,4-thiazolidinedione hydrochloride
CAS Number: 146062-44-4
Current Sponsor code: MIN-102
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 15-
Pharmaceutical form of the placebo: Oral suspension
Route of administration of the placebo: Oral use

Primary Outcome(s)

Primary end point(s): Main Study:
1. Efficacy: Change from baseline to week 96 in the total walking distance in the 6MWT

Extension Study:
1. Long-term safety and tolerability assessed in terms of AE, SAE, SUSARs, Vitals signs, ECG, Clinical Laboratory tests

Secondary Objective: Main Study:
Efficacy objectives: To evaluate the effects of MIN-102 after 96 weeks of treatment on:
• Change from baseline in body sway amplitude
• Comprehensive clinical rating scales (SSPROM and EDSS)
• Clinician and patient global impression of symptom severity and change
• Muscle strength
• Quality of life
• Incidence of cerebral inflammatory lesions.
Safety objectives: To evaluate the safety and tolerability of MIN-102 compared with placebo
Exploratory objectives- To evaluate the effects of MIN-102 on various biochemical markers in plasma and cerebrospinal fluid (CSF), and spinal cord imaging parameters.

Extension Study:
To evaluate the long-term effects of MIN-102 on:
• Change from baseline in 6MWT and body sway
• Comprehensive clinical rating scales (SSPROM and EDSS)
• Quality of life
• Incidence of cerebral inflammatory lesions.
Exploratory objectives- To assess the long-term effects of MIN-102 on various biochemical markers in plasma.

Timepoint(s) of evaluation of this end point: During treatment period

Main Objective: Main Study:
Efficacy of MIN-102 on the progression of adrenomyeloneuropathy (AMN) in male patients as determined by the change from baseline in Six-Minute Walk Test (6MWT) compared with placebo after 96 weeks of treatment.

Extension Study:
To assess the safety and tolerability of MIN-102 upon long-term treatment.

Secondary Outcome(s)

Secondary end point(s): Main Study:
1. Changes from baseline to week 96 in the following:
• Body sway amplitude
• Comprehensive clinical rating scales (SSPROM, EDSS)
• Clinician and patient global impression Scales (CGI-S, CGI-I, PGI-I)
• Dynamometry
• Quality of Life Assessments (EQ-5D-5L, MSWS-12, Qualiveen-SF and IIEF)
• Cerebral MRI (incidence of inflammatory lesions)
2. Safety : Assessed in terms of AE, SAE, SUSARs, Vitals signs, ECG, Clinical Laboratory tests

Extension Study:
Changes from the baseline to the last scheduled on-study assessment for the following variables:
• 6MWT
• Body sway amplitude
• Comprehensive clinical rating scales (SSPROM, EDSS)
• Quality of Life Assessments (EQ-5D-5L, MSWS-12, Qualiveen-SF and IIEF)
• Cerebral MRI (incidence of inflammatory lesions)

Timepoint(s) of evaluation of this end point: During treatment period

Secondary ID(s)

MT-2-01

Source(s) of Monetary Support

Minoryx Therapeutics S.L.