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

A Randomized Open-label Phase 2a Study to Assess PXL770 After 12 Weeks of Treatment in Male Subjects With Adrenomyeloneuropathy (AMN) Form of X-linked Adrenoleukodystrophy (X-ALD or ALD)

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).

Study Overview

• Status: Withdrawn
• Conditions: Adrenomyeloneuropathy
• Intervention / Treatment: Drug: PXL770

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 Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PXL770 500 mg QD	Drug: PXL770; Tablet
Experimental: PXL770 250 mg BID	Drug: PXL770; Tablet

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Poxel SA

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2023
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: November 16, 2021
• First Submitted That Met QC Criteria: December 3, 2021
• First Posted (Actual): December 6, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neurologic Manifestations; Endocrine System Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Neurobehavioral Manifestations; Demyelinating Diseases; Heredodegenerative Disorders, Nervous System; Adrenal Gland Diseases; Mental Retardation, X-Linked; Intellectual Disability; Genetic Diseases, X-Linked; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Hereditary Central Nervous System Demyelinating Diseases; Leukoencephalopathies; Adrenal Insufficiency; Peroxisomal Disorders; Adrenoleukodystrophy
• Other Study ID Numbers: PXL770-011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share IPD with other researchers

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No