Study to Assess PXL770 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 PXL770 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 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.

Official Title
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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)

Conditions
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Adrenomyeloneuropathy

Intervention / Treatment
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* Drug: PXL770


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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PXL770 500 mg QD<br> | Drug: PXL770<br>* Tablet<br>|
| Experimental: PXL770 250 mg BID<br> | Drug: PXL770<br>* Tablet<br>|

What is the study measuring?
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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 |