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: 3 October 2023
• Main ID: EUCTR2017-000748-16-NL
• Date of registration: 10/07/2017
• 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: 23/11/2017
• 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, Poland, 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. Provision of written informed consent to participate in the main study.
2. Male patients aged =18 to =65 years.
3. Diagnosis of ALD based on genetic testing.
4. Clinical evidence of spinal cord involvement, with an EDSS score between 2 and 6.
5. Ability to walk for 6 minutes, without or with rest, with usual walking aids (e.g. leg braces, cane or crutch).
6. Ability to stand on a force plate with closed eyes and with feet apart for a minimum of 20 seconds.
7. Either a normal brain MRI or a type-1 through type-5 pattern MRI abnormality in which the abnormality does not show presence of inflammation. Note: MRI is not required at V-1 if an MRI was obtained within the 6 months prior to the first day of screening.
8. Normal adrenal function or appropriate steroid replacement if adrenal insufficiency is present.
9. Patients who are surgically sterilized. If not surgically sterilized, patients should be willing to use adequate contraception and not donate sperm from the first dose of the study medication until 90 days after the follow-up visit. Adequate contraception for the male patient (and his female partner, if of childbearing potential) is defined as hormonal contraceptives or an intrauterine device combined with at least 1 of the following forms of contraception: a diaphragm or cervical cap, or a condom. Total abstinence, in accordance with the lifestyle of the patient, is also acceptable.

Extension Study:
1. Completion of the entire 96-weeks double-blind period of the study (Part 1).
2. Provision of written informed consent to participate in the extension study part.
3. Normal adrenal function or appropriate steroid replacement if adrenal function has changed during the double-blind treatment phase.
4. The following inclusion criteria of Part 1 will be modified:
• age =18 to =65 years will no longer apply.
• EDSS score between 2 and 6 will no longer apply.
• Ability to walk for 6 minutes will no longer apply. If a patient is unable to walk for 6 minutes, the maximum time and walking distance will be recorded. If a patient is unable or refuses to walk at all, this will also be recorded.
• Ability to stand on a force plate with eyes closed and feet apart for a minimum of 20 seconds will no longer apply. If a patient is no longer able to stand on a force plate for 20 seconds, this test will not be conducted.
• Either a normal brain MRI or a type-1 through type-5 pattern MRI abnormality in which the abnormality does not show presence of inflammation (gadolinium enhancement) will no longer apply.
In case of brain MRI lesions making the patient eligible for HSCT, he is still eligible for the extension study, but treatment will be discontinued immediately before any transplant-related treatment is initiated.
• A stable dose of Lorenzo´s Oil, botulinum toxin, N-acetylcysteine, baclofen, benzodiazepines, opiates and cannabis preparations, fampidrine and antioxidants will no longer apply.

All other inclusion criteria of Part 1 remain in place.

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. Current treatment with immunosuppressant medication, except for corticosteroids.
5. 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.
6. Reduced left-ventricular ejection fraction, or other clinically significant cardiac abnormalities on echocardiogram that in the investigator's opinion could predispose the subject to volume overload or its attendant consequences.
7. A positive result on laboratory tests for hepatitis B surface antigen, hepatitis C antibody and human immunodeficiency virus antibody.









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

Health Condition(s) or Problem(s) studied

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

ADRENOMYELONEUROPATHY IN MALE PATIENTS WITH X-LINKED ADRENOLEUKODYSTROPHY

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)

Secondary Objective: Main Study:
To evaluate the effects of MIN-102 after 96 weeks of treatment on:
•Change from baseline in body sway amplitude (in four states: eyes closed/feet apart, eyes open/feet apart, eyes closed/feet together, eyes open/feet together)
•Comprehensive clinical rating scales (Severity Score System for Progressive Myelopathy [SSPROM] and Expanded Disability Status Scale [EDSS])
•Clinician and patient global impression of symptom severity and change
•Muscle strength
•Quality of life
•Incidence of progression of cerebral lesions.
• Loes severity score

Extension Study:
Secondary objectives- To evaluate the long-term effects of MIN-102 on:
•Change from baseline in 6MWT and body sway (in four states: eyes closed/feet apart, eyes open/feet apart, eyes closed/feet together, eyes open/feet together)
•Comprehensive clinical rating scales (SSPROM and EDSS)
•Quality of life
•Incidence of progression of cerebral lesions.

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.

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

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

Secondary Outcome(s)

Secondary end point(s): Main Study:Secondary efficacy endpoints are changes from baseline to week 96 in the following:
• Body sway amplitude (in four states: eyes closed/feet apart, eyes open/feet apart, eyes closed/feet together, eyes open/feet together)
• SSPROM
• EDSS
• Clinical Global Impressions - Severity (CGI-S)
• Clinical Global Impressions - Improvement (CGI-I)
• Patient Global Impressions - Improvement (PGI-I)
• Dynamometry
• Quality of Life Assessments
- European Quality of Life 5 Dimensions (EQ-5D-5L)
- Multiple Sclerosis Walking Scale (MSWS-12)
- Qualiveen Short Form quality of life questionnaire for urinary disorders (Qualiveen-SF)
- International Index of Erectile Function questionnaire (IIEF)
• Cerebral MRI (incidence of inflammatory lesions).

Extension Study:
The efficacy endpoints are the changes from the baseline of Part 2 (V6) to the last scheduled on-study assessment for the following variables:
• 6MWT (only through to end of visit 11)
• Body sway amplitude (in four states: eyes closed/feet apart, eyes open/feet apart, eyes closed/feet together, eyes open/feet together)
• SSPROM
• EDSS
• Quality of Life Assessments (EQ-5D-5L, MSWS-12, Qualiveen-SF and IIEF)(only through to end of visit 11).
• Cerebral MRI (incidence of inflammatory lesions).

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

Secondary ID(s)

2017-000748-16-GB

MT-2-01

Source(s) of Monetary Support

Minoryx Therapeutics S.L.

Ethics review

Status: Approved
Approval date: 23/11/2017
Contact: