Cerebral X-linked Adrenoleukodystrophy (cALD) MedDRA version: 20.0 Level: PT Classification code 10051260 Term: Adrenoleukodystrophy System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Minoryx Therapeutics S.L.
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Written informed consent by parent/legal guardian, or authorized legal representative to participate in the study 2. Males aged =2 and =12 years with a diagnosis of X-linked ALD based on genetic testing; or, in absence of genetic testing, elevation of VLCFA and confirmed by family history of X-ALD with clinical symptoms and elevation of VLCFA or by genetic testing of a family member. 3. White matter involvement as determined by cerebral MRI lesions without Gd enhancement at baseline (Population 1), or with Gd enhancement at baseline (Population 2). 4. Major Functional Disabilities (MFD) score of 0, as determined by key measures in the Neurological Function Scale (NFS) 5. Baseline Loes score >0 and =10 6. Baseline Gadolinium Intensity Score (GIS) =3 7. No signs or symptoms of adrenal insufficiency and morning cortisol and aldosterone levels within normal laboratory ranges for age, or appropriate steroid replacement if adrenal insufficiency is present. A history of adrenal insufficiency is not exclusionary if the foregoing is currently met. 8. Glycated hemoglobin (HbA1c) within normal range Are the trial subjects under 18? yes Number of subjects for this age range: 13 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Other chronic neurological disease 2. Known intolerance to pioglitazone or other thiazolidinediones 3. Use of pioglitazone or other thiazolidinediones within the past 6 months prior to screening 4. Use of biotin at a daily dose of >50 mg per day within the past 3 months prior to screening 5. Current participation in another interventional clinical study or participation in such a study within 6 months prior to screening 6. Previous HSCT 7. Requirement for a prohibited concomitant medication (section 3.4.10) 8. Previous or current history of bladder polyps, bladder cell hyperplasia, or cancer (other than successfully treated basal cell carcinoma) 9. Previous or current history of congestive heart failure 10. Clinically significant anemia with hemoglobin 2 times the ULN or total bilirubin >1.5 times the ULN (unless due to Gilbert's syndrome) 12. Moderate or severe hepatic impairment (groups B and C according to Child-Pugh classification) 13. eGFR 6.4% and fasting blood glucose levels = 0.9 times the lower limit of normal and = 1.1 times the upper limit of normal at Screening 18. Contraindication to MRI procedure, such as presence of ferromagnetic materials (aneurysm clips, pacemaker, intraocular metal, cochlear implant) in the body 19. Conditions that could modify the absorption of the study drug 20. Inability or unwillingness of parent/legal guardian or subject to comply with the study procedures 21. Inability or unwillingness of parent/legal guardian or subject to resume standard of care at a local center once study is complete or criteria for HSCT is met and treatment available. 22. Other medical, neurologic, psychiatric, or social condition that, in the opinion of the investigator, is likely to unfavorably alter risk-benefit of study participation, confound interpretation of safety or efficacy results, or interfere with the satisfactory completion of study requirements
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to evaluate whether MIN-102 can halt disease progression of cALD at week 96, as determined by serial clinical and magnetic resonance imaging (MRI) investigations in pediatric subjects.;Secondary Objective: To determine the effects of MIN-102 treatment on further clinical and imaging parameters. • To assess the changes in neurological function. • To evaluate the effects of pre-HSCT MIN-102 treatment on: - Loes scores - Gadolinium intensity score (GIS) - Overall survival of patients who have not undergone HSCT - Number of patients meeting HSCT criteria • To assess the pharmacokinetics (PK), safety, tolerability, and palatability of MIN-102 in pediatric subjects;Primary end point(s): The primary efficacy endpoint will be the number of patients meeting "arrested disease" criteria at Visit 8 and Visit 12.;Timepoint(s) of evaluation of this end point: From Baseline to Visit 8 and Visit 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: Change from Baseline;Secondary end point(s): • Sustained change from Baseline in the score composed of NFS items 1 (hearing/auditory processing), 2 (aphasia/apraxia), 4 (vision impairment), 10 (spastic gait) and 13 (incontinence) • Sustained change from Baseline in total NFS score "Sustained change" is defined as the same total score for NFS items 1, 2, 4, 10, and 13 and no change >1 in NFS total score observed in two the consecutive Visits 6–8, and Visits 11-12, respectively. If "sustained change" definition is not met, the average of the two scores of Visit 6 and 8, and Visit 11 and 12, respectively, will be used. If NFS total score differs by 1 point between V6-8, or V11-12, the higher of the two scores is used. • Change from baseline in Loes MRI severity score • Change from baseline in Gadolinium Intensity Score (GIS) • Overall survival of patients who have not undergone HSCT • Number of patients meeting HSCT criteria | — |
Countries
Argentina, France, Germany, Spain, United States
Contacts
Public ContactClinical Operations
Minoryx Therapeutics S.L.
Outcome results
None listed