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.