Adrenoleukodystrophy
Conditions
Interventions
Subjects will be randomized in a 1:1 ratio in one of the 2 treatment groups to
receive either:
- PXL770 500mg OD
- PXL770 250mg BID
during 12 weeks
500mg OD treatment group
2 tablets per day in one
Sponsors
Poxel S.A.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Male subjects with either a confirmed diagnosis of AMN by genetic testing (mutation in the ATP binding cassette subfamily D (ABCD1 gene)) or a family history of X-linked adrenoleukodystrophy (ALD) together with an elevation in VLCFA obtained from overnight fasting plasma sample at Screening Visit (V1). 2. Age: >= 18 to
Exclusion criteria
Exclusion criteria: Target disease exclusions 1. Any progressive neurological disease other than AMN. 2. Arrested or progressing C-ALD as defined by cerebral lesions (except for non-specific abnormalities that can be observed in AMN subjects). 3. Prior receipt of an allogeneic hematopoietic stem cell transplant or gene therapy. Medical history and concurrent disease exclusions Cardiovascular diseases 4. Any uncontrolled cardiovascular disorder in addition to those listed in Exclusion Criteria #5, 6 and 7 that prevents subject*s participation in the study per Investigator*s judgement. 5. Unstable arrhythmia or clinically significant arrhythmia diagnosed during the Screening Period, long QT syndrome, short QT syndrome, history of drug-induced Torsade de Pointes. 6. Uncontrolled high blood pressure (BP): diastolic BP >= 100 mmHg or systolic BP >= 160 mmHg with or without antihypertensive treatment at V1. 7. Any of the following disease within 6 months prior to V2: - Myocardial infarction - Unstable congestive heart failure - Heart failure Class III or IV according to the New York Heart Association (NYHA) - Coronary revascularization (coronary artery bypass graft (CABG) / percutaneous transluminal coronary angioplasty (PTCA)) - Unstable angina - Transient ischemic attack, stroke or cerebrovascular disease. Other diseases 8. Estimated glomerular filtration rate (eGFR) 2 x the upper limit of normal (ULN) at V1). 11. Type 1 diabetes mellitus. 12. Type 2 diabetes mellitus (T2DM) if not on stable treatment (i.e., same doses and same drug(s)) for at least 6 months prior to V1 or uncontrolled T2DM (glycated hemoglobin (HbA1c) > 7.5% at V1). 13. Uncontrolled hypothyroidism (thyroid stimulating hormone (TSH) > 2 x ULN at V1). Other exclusion conditions 14. Contra-indications for MRI procedure (e.g., the presence of paramagnetic materials in the body, such as aneurysm clips, pacemakers, intraocular metal or cochlear implants including allergies to anesthetics or contrast agents and claustrophobia). 15. Positive screen at V1 for hepatitis B surface antigen (HbsAg), antibody to the hepatitis C virus (Anti-HCV) with detected circulating ribonucleic acid (RNA), antibodies to human immunodeficiency (Anti-HIV) 1 and 2 virus. 16. Any excessive alcohol intake (>= 14 units of alcohol/week) within 1 year prior to V2, where a unit of alcohol equals approximately 250 mL of beer, 100 mL of wine, or 35 mL of spirits. 17. Any recent drug abuse (< 6 months prior to V2) or medically uncontrolled current drug dependence per Investigator*s judgement (e.g.: opiate, tetrahydrocannabinol / cannabidiol, etc.). 18. Immunocompromised subjects such as subjects that underwent organ transplantation. 19. Any other known serious disease or other disease which in the Investigator*s opinion would exclude the subject from the study. 20. Mental handicap, limited capacity of recognition, inability
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary plasma PK parameters of PXL770: Cmax and AUC0-24 at V3 for 500mg OD treatment group and Cmax and AUC0-8 at V3 for 250mg BID treatment group. | — |
Secondary
| Measure | Time frame |
|---|---|
| - Pharmacokinetics Secondary plasma PK parameters of PXL770: o Ctrough at V3, V4 (Week 8) and V5-EoT, o Cavg, CLss/F, AUC0-8 (for 500mg OD treatment group), tmax and AUClast at V3. - Safety Safety and tolerability will be assessed on the following parameters: o Adverse events (AEs) o Physical examination o Weight, Body Mass Index (BMI) o BP, heart rate (HR) o 12-lead electrocardiogram (ECG) o Biological parameters: biochemistry, hematology, coagulation o Urinalysis - Pharmacodynamics Change from baseline in the following parameters: o VLCFA in plasma in fasting conditions: C26:0, C26:0-Lyso-phosphatidylcholine (Lyso-PC), C24:0 and C22:0 o NfL in plasma o Lipids in serum: total cholesterol, high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), triglycerides o Glycemic parameters: fasting serum glucose and HbA1c | — |
Countries
Netherlands
Outcome results
None listed