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
Interventions
Product Name: 5-[4-[2-(5-(1-hydroxyethyl)-2- pyridinyl)ethoxy]benzyl]-2,4- thiazolidinedione hydrochloride
Pharmaceutical Form: Oral suspension
INN or Proposed INN: Ler
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 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 GIS =2 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: 10 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. Current use of immunosuppressant medication, excluding corticosteroids 8. Requirement for a prohibited concomitant medication 9. Previous or current history of bladder polyps, bladder cell hyperplasia, or cancer (other than successfully treated basal cell carcinoma) 10. Previous or current history of congestive heart failure 11. Clinically significant anemia with hemoglobin 2 times the ULN or total bilirubin >1.5 times the ULN (unless due to Gilbert's syndrome) 13. Moderate or severe hepatic impairment (groups B and C according to Child-Pugh classification) 14. Chronic kidney disease stage 3 or higher (according to chronic kidney disease staging by The Renal Association) 15. Pulmonary disease or cardiac disease of sufficient severity to limit participation in the study and/or completion of study procedures 16. 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 17. Contraindication to MRI procedure, such as presence of paramagnetic materials (aneurysm clips, pacemaker, intraocular metal, cochlear implant) in the body 18. Conditions that could modify the absorption of the study drug 19. Inability or unwillingness of parent/legal guardian or subject to comply with the study procedures 20. 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: To evaluate the effects of MIN-102 on the progression of cerebral lesions from baseline to immediately prior to hematopoietic stem-cell transplantation (HSCT), as determined by serial magnetic resonance imaging (MRI) in pediatric subjects.; Secondary Objective: • To evaluate the effects of pre-HSCT MIN-102 treatment on: - Loes scores - Gadolinium intensity score (GIS) • To assess the pharmacokinetics (PK), safety, tolerability, and palatability of MIN-102 in pediatric subjects • To assess the changes in neurological function from baseline to immediately before decision to HSCT ; Primary end point(s): Progression of cerebral lesions, as determined by serial MRI, using the following parameters: • First appearance and time to first appearance of Gd-enhancing cerebral lesions in subjects not showing these lesions at baseline in Population 1 • Change from baseline to immediately prior to HSCT in the T1 and T2/FLAIR volume of Gd-enhancing cerebral lesions in Population 2 • Progression of FLAIR based overall lesion burden volume, assessed in both Populations ;Timepoint(s) of evaluation of this end point: From Baseline to immediately prior to HSCT | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change from baseline to immediately prior to HSCT, or decision not perform HSCT, in Loes MRI severity score • Change from baseline to immediately prior to HSCT, or decision not perform HSCT in GIS • Changes from baseline to immediately prior to HSCT, or decision not perform HSCT in: - Total score of Neurological Function Score (NFS) - Total score of the 6 Major Functional Disabilities (MFD) of the NFS ;Timepoint(s) of evaluation of this end point: From Baseline to immediately prior to HSCT | — |
Countries
Germany, Spain
Contacts
Public ContactClinical Operations
Minoryx Therapeutics S.L.
Outcome results
None listed