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.

Study Overview

• Status: Terminated
• Conditions: Phenylketonurias; PKU

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 7

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente Los Angeles Medical Center
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County
  • Florida
    • Tampa, Florida, United States, 33606
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
  • Indiana
    • Topeka, Indiana, United States, 46571
      • Community Health Clinic
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • University of Pittsburgh Medical Center- CHOP
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84018
      • University of Utah Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults with diagnosed PKU due to PAH deficiency

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma phenylalanine (Phe) concentrations	Change in plasma Phe concentrations throughout study duration	Baseline to Week 52
Plasma tyrosine (Tyr) concentrations	Change in plasma Tyr concentrations throughout study duration	Baseline to Week 52
Quality of life (QOL), as assessed using the PKU-QOL questionnaire measures	Changes in PKU-QOL	Baseline to Week 52

Collaborators and Investigators

• Sponsor: Homology Medicines, Inc

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2021
• Primary Completion (Actual): February 1, 2023
• Study Completion (Actual): August 1, 2023

Study Registration Dates

• First Submitted: February 18, 2021
• First Submitted That Met QC Criteria: February 22, 2021
• First Posted (Actual): February 24, 2021

Study Record Updates

• Last Update Posted (Actual): August 25, 2023
• Last Update Submitted That Met QC Criteria: August 24, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Amino Acid Metabolism, Inborn Errors; Phenylketonurias
• Other Study ID Numbers: HMI-100-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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