Study to Assess PXL065 in Subjects With Adrenomyeloneuropathy (AMN) Form of X-linked Adrenoleukodystrophy (X-ALD or ALD)

Study Overview
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Brief Summary
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A randomized open-label Phase 2a study to assess the pharmacokinetics and pharmacodynamic parameters of PXL065 after 12 weeks of treatment in male subjects with adrenomyeloneuropathy (AMN).

Detailed Description
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A randomized open-label Phase 2a study to assess the pharmacokinetics and pharmacodynamic parameters of PXL065 after 12 weeks of treatment in male subjects with adrenomyeloneuropathy (AMN). There will be a total of 3 study periods. Screening period of a maximum of 4 weeks prior to the open-label Treatment Period (Baseline Visit - V2). This period can be exceptionally extended for 2 weeks Open-label Treatment Period of 12 weeks Follow-up Period of 2 weeks after the last intake of the treatment (V5-End of Treatment Visit (EoT)). During the treatment period, very long chain fatty acids (VLCFA) will be assessed every 4 weeks, to evaluate the kinetics of the PXL065 effect. Neurofilament light (NfL) will be assessed after 8 and 12 weeks of treatment, and other exploratory biomarkers after 12 weeks of treatment. A follow up period will allow continued monitoring the subjects' safety and evaluation of the kinetics of the 2 main biomarkers (VLCFA and NfL) at 2 weeks after the last intake of the treatment.

Official Title
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An Open-label Phase 2a Study to Assess the Pharmacokinetics and Pharmacodynamic of PXL065 Parameters After 12 Weeks of Treatment in Male Subjects With Adrenomyeloneuropathy (AMN) Form of X-linked Adrenoleukodystrophy (X-ALD or ALD)

Conditions
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ALD (Adrenoleukodystrophy)

Intervention / Treatment
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* Drug: PXL065


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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). Age: ≥ 18 to ≤ 65 years at informed consent signature. 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 Exclusion Criteria: Any progressive neurological disease other than AMN. Arrested or progressing C-ALD as defined by cerebral lesions (except for non-specific abnormalities that can be observed in AMN subjects). Prior receipt of an allogeneic hematopoietic stem cell transplant or gene therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PXL065<br>PXL065 22.5 mg QD | Drug: PXL065<br>* PXL065 22.5 mg QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic | Deuterated and protonated forms of (R)-pioglitazone and (S)-pioglitazone: Cmax | Week 4 | 
| PharmacoKinetic | Deuterated and protonated forms of (R)-pioglitazone and (S)-pioglitazone: AUC0-24 (AUCtau) | Week 4 |