A Clinical Study to Assess the Efficacy and Safety of Leriglitazone in Adult Male Subjects With Cerebral Adrenoleukodystrophy

Study Overview
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Brief Summary
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A Clinical Study to Assess the Efficacy and Safety of Leriglitazone in Adults Male Subjects with Cerebral Adrenoleukodystrophy.

Official Title
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A Clinical Study to Assess the Efficacy and Safety of Leriglitazone in Adult Male Subjects With Cerebral Adrenoleukodystrophy

Conditions
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Cerebral Adrenoleukodystrophy (cALD)

Intervention / Treatment
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* Drug: Leriglitazone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Subject is male and aged ≥18 years. Subject has progressive cALD, defined as GdE+ brain lesions. Subjects for whom HSCT is not recommended by the investigator or subject is not willing to undergo HSCT. Subject has a Loes score ≥0.5 and ≤12 at Screening. Subject does not have major functional disability in the Major Functional Disabilities-Neurological Function Score (MFD-NFS), except for wheelchair bound or total incontinence, which will be allowed as these are considered expected symptoms of AMN in the time course of the disease Subject does not have major cognitive impairment which would impair his ability to take part in the study as determined by the investigator at screening. Key Exclusion Criteria: Subject who had previous bone marrow transplantation (HSCT) or treatment with ex-vivo gene therapy (eli-Cel). Subject has known type 1 or type 2 diabetes. Subject has known hypersensitivity or intolerance to pioglitazone or any other thiazolidinedione. Subject is taking or has taken honokiol, pioglitazone, or other thiazolidinediones within 3 months prior to Screening. Subject with current participation in another interventional clinical study or within 1 month prior to Screening. Subject with other medical, neuropsychiatric or social conditions that, in the opinion of the investigator, are likely to adversely affect the risk-benefit of study participation, interfere with study compliance, or confound the study results.

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Leriglitazone<br>Leriglitazone Treatment | Drug: Leriglitazone<br>* Leriglitazone at a strength of 15 mg/ml. Once-daily dosing at an initial volume of 10 ml<br>|
| Placebo Comparator: Placebo<br>Placebo | Drug: Placebo<br>* Placebo will match the study drug visually and by taste<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint will be the time to death or the subject becoming bedridden with a requirement for permanent ventilatory support, wichever comes earlier, in subjects treated with leriglitazone compared to placebo. | The primary endpoint will be the time to death or the subject becoming bedridden with a requirement for permanent ventilatory support, wichever comes earlier, in subjects treated with leriglitazone compared to placebo. | Interim analysis 1 (at 18 months of treatment) | 
| The primary endpoint will be the time to death or the subject becoming bedridden with a requirement for permanent ventilatory support, wichever comes earlier, in subjects treated with leriglitazone compared to placebo. | The primary endpoint will be the time to death or the subject becoming bedridden with a requirement for permanent ventilatory support, wichever comes earlier, in subjects treated with leriglitazone compared to placebo. | Interim analysis 2 (at 27 months of treatment) | 
| The primary endpoint will be the time to death or the subject becoming bedridden with a requirement for permanent ventilatory support, wichever comes earlier, in subjects treated with leriglitazone compared to placebo. | The primary endpoint will be the time to death or the subject becoming bedridden with a requirement for permanent ventilatory support, wichever comes earlier, in subjects treated with leriglitazone compared to placebo. | Final analysis (at 36 months of treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Loes Score. | Change from Baseline in Loes Score. Loes Score Minimum = 0 Maximum =34 0 better outcome (healthy) 34 worst osutcome | Interim analysis 1 (at 18 months of treatment) | 
| Change from Baseline in Loes Score | Change from Baseline in Loes Score. Loes Score Minimum = 0 Maximum =34 0 better outcome (healthy) 34 worst osutcome | Interim analysis 2 (at 27 months of treatment) | 
| Change from Baseline in Loes Score | Change from Baseline in Loes Score. Loes Score Minimum = 0 Maximum =34 0 better outcome (healthy) 34 worst osutcome | Final analysis (at 36 months of treatment) |