A randomized open-label Phase 2a study to assess the pharmacokinetics and pharmacodynamic parameters of PXL770 after 12 weeks of treatment in male subjects with adrenomyeloneuropathy (AMN)

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 <= 65 years at informed consent signature.
3. Normal brain magnetic resonance imaging (MRI) or brain MRI showing
non-specific abnormalities that can be observed in AMN subjects without signs
of cerebral form of ALD (C-ALD). MRI must be performed within 6 months prior to
V2. If there is no available brain MRI within this period, a brain MRI must be
performed before V2.
4. Appropriate steroid/adrenal hormone replacement if adrenal insufficiency is
present.
5. Subjects with female partners of childbearing potential must agree to remain
sexually abstinent or use condoms during the treatment phase until 2 weeks
after the last IP intake. In addition, subjects must be willing to stop sperm
donation during this time.
6. Capable of providing written informed consent. Subjects must have given
written informed consent before any study-related activities are carried out.

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)
<= 60 mL/min/1.73m² at V1 calculated by the chronic kidney disease -
epidemiology collaboration (CKD-EPI) formula.
9. Active malignancy or malignancy with a complete remission date within 2
years prior to V2 (except for treated basal cell carcinoma or treated squamous
cell carcinoma of the skin).
10. Uncontrolled hepatic disorder (aspartate aminotransferase (AST) or alanine
aminotransferase (ALT) > 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 to follow the
study procedures as evaluated by the Investigator.
21. Known hypersensitivity to any of the constituents or excipients of the IP,
or history of relevant drug and/or food allergies (e.g., anaphylactic,
anaphylactoid reactions).
22. Use of Lorenzo*s oil, peroxisome proliferator-activated receptor γ (PPARγ)
agonists (including thiazolidinediones), valproic acid, bezafibrate, or
4-phenyl-butyrate (4PBA) within 3 months prior to V1 and/or between V1 and V2.
23. Use of statins, vitamin A, E or lipoic acid or dietary regimens and any
other medication (including vitamins, herbal and dietary supplements) taken for
AMN unless the dosing regimen of any of these has been stable for at least 3
months prior to V1 and between V1 and V2.
24. Use of non-permitted medications related to the risk of drug-drug
interaction (DDI) at V2: cytochrome P450 (CYP) 1A2 sensitive substrates
(agomelatine, alosetron, duloxetine, melatonin, pirfenidone, ramelteon,
selegiline, tacrine, tasimelteon, tizanidine, clozapine, olanzapine).
If the subject is eligible based on all other inclusion/exclusion criteria and
if medically acceptable as per investigator's judgement, these medications
should be stopped or switched prior to V2 otherwise subject should be withdrawn
from the study.
25. Participation in another clinical study with intake of an active
investigational product (e.g.: PPARγ and PPAR* agonists, Thyroid Hormone
Receptor β (THRβ) agonists*) during the last 3 months prior to V1.