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

Phase 2

Withdrawn

• Conditions: ALD (Adrenoleukodystrophy)
• Interventions: Drug: PXL065

• Registration Number: NCT05200104
• Lead Sponsor: Poxel SA

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2022-01-06
• Study First Submitted QC: 2022-01-06
• Study First Posted: 2022-01-20
• Study Start: 2023-09
• Primary Completion: 2024-09
• Study Completion: 2024-09
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-10
• Last Update Posted: 2024-12-16

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Male
• Target Recruitment: 12

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
PXL065	PXL065	PXL065 22.5 mg QD

Primary Outcome Measures

Name	Time	Method
PharmacoKinetic	Week 4	Deuterated and protonated forms of (R)-pioglitazone and (S)-pioglitazone: AUC0-24 (AUCtau)
Pharmacokinetic	Week 4	Deuterated and protonated forms of (R)-pioglitazone and (S)-pioglitazone: Cmax