Natural History Clinical Study in Adult PKU

A Prospective Study Investigating the Natural History of Adults With Phenylketonuria (PKU) Due to Phenylalanine Hydroxylase Deficiency

The objective of this study is to characterize the natural history of phenylketonuria (PKU) due to phenylalanine hydroxylase (PAH) deficiency in adults through prospective collection of clinical, cognitive, and quality of life assessments.

Phenylalanine hydroxylase (PAH) deficiency is a rare disease caused by an inborn error of metabolism. If left untreated, PAH deficiency results in progressive, irreversible neurological impairment during infancy and early childhood.

This study is designed to collect information about important PKU-related symptoms and tests to characterize the natural history of PKU due to PAH deficiency in a selected sample of adults. No new investigational treatment will be administered to participating patients.

Key Inclusion Criteria:

• Aged 18-55 years at the time of informed consent
• Diagnosis of PKU due to PAH deficiency
• One plasma Phe value with a concentration of ≥ 600 μmol/L drawn at Screening and at least 1 historical Phe value ≥ 600 μmol/L in the preceding 12 months

Key Exclusion Criteria:

• Subjects with PKU that is not due to PAH deficiency
• Alanine aminotransferase (ALT) > 1.5x upper limit of normal (ULN) and aspartate aminotransferase (AST) >1.5x ULN
• Alkaline phosphatase > 1.5x ULN
• Total bilirubin > 1.5x ULN, direct bilirubin ≥ 1.5x ULN, unless associated with Gilbert's syndrome.
• Serum creatinine > 1.5x ULN
• Hematology values outside of the normal range (hemoglobin < 11.0 g/dL for males or < 10.0 g/dL for females; white blood cells (WBC) < 3,000/μL; absolute neutrophils < 1,500/μL; platelets < 100,000/μL)
• Hemoglobin A1c > 6.5% or fasting glucose > 126 mg/dL
• Any clinically significant abnormal laboratory result at Screening, as determined by the Investigator