Study to Assess PXL770 in Subjects With Adrenomyeloneuropathy (AMN) Form of X-linked Adrenoleukodystrophy (X-ALD or ALD)

Phase 2

Withdrawn

• Conditions: Adrenomyeloneuropathy
• Interventions: Drug: PXL770

• Registration Number: NCT05146284
• Lead Sponsor: Poxel SA

Brief Summary

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).

Detailed Description

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).

There are 3 study periods.

* Screening Visit: within a maximum of 4 weeks prior to the open-label Treatment Period

* Open-label Treatment Period: 12 weeks

* Follow-up Period: 2 weeks after the last intake of the treatment

During the treatment period, VLCFA will be assessed every 4 weeks, to evaluate the kinetics of the effect. 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 monitoring the subjects' safety as well as the duration of the effect on the 2 main biomarkers (VLCFA and NfL) at 2 and 4 weeks after the drug withdrawal.

Study Timeline

• Study First Submitted: 2021-11-16
• Study First Submitted QC: 2021-12-03
• Study First Posted: 2021-12-06
• 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• Status: WITHDRAWN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: 24

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: PARALLEL

Arm && Interventions

Group	Intervention	Description
PXL770 500 mg QD	PXL770	-
PXL770 250 mg BID	PXL770	-

Primary Outcome Measures

Name	Time	Method
Pharmacokinetic (PK) parameters	4 week	Peak plasma concentration (Cmax) for 500mg QD
Pk parameters	4 week	Area under the plasma concentration versus time curve (AUC)0-24 for 500mg QD
PK parameters	4 week	AUC0-8 for 250mg BID