The Effectiveness of Kuvan in Amish PKU Patients

• Status: Recruiting
• Trial end date: 2018-08-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to determine if Amish patients with PKU show responsiveness after a high dose, prolonged Saproterin trial. The population of interest has a high frequency of a specific splice site mutation, the 1066-11G>A mutation. This splice site mutation activates a cryptic splice site resulting in an in frame insertion of 9 nucleotides preceding exon 11. This leads to protein conformational changes and abrogation of function. Previous studies of this genotype have indicated <1% residual activity of the PAH enzyme and an insignificant responsiveness to Saproterin. However, in this specific study Phe levels were evaluated only over 24 hours after a single-dose BH4 challenge at the standard dose of 20mg/kg.

Based on new clinical information, the investigators hypothesize that if given a prolonged trial of Saproterin at a higher dose, Amish patients with PKU, specifically those homozygous for the c.1066-11G>A mutation, will have a significant reduction in Phe levels or an increase in Phe tolerance and/or improvement in executive functioning and quality of life.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospitals Cleveland Medical Center
• Collaborator: BioMarin Pharmaceutical

Criteria

Inclusion Criteria:

• Current diagnosis of PKU with the following:

• Age of at least 2 years or older

• Baseline Phe level of > 360 umol/L

• Willing to maintain a stable diet

• Patient or guardian are willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to any research-related procedures

• Are willing to comply with all study procedures

• Two identifiable mutations found on PAH gene sequencing

• Any patients already taking Saproterin (or have taken in the past), must have a treatment end date at least 14 days prior to Day 1 of the study.

Exclusion Criteria:

• Any patient currently taking Saproterin who has taken the medication at any point in the 14 days prior to Day 1 of the study

• Under 2 years of age

• Unwilling to maintain a stable diet

• Patients with baseline Phe levels < 360 umol/L

• Patients unable to comply with all study procedures

• Patients unable to provide written, signed informed consent

• One (or no) identifiable mutations found on PAH gene sequencing