Principal Investigator: Nicola Longo
Keywords: PKU , Kuvan Department: Pediatric Genetics
IRB Number: 00035105 Co Investigator: Ashley  Warnock
Specialty: Pediatric Genetics
Sub Specialties: Medical Genetics
Recruitment Status: Active, not recruiting

Contact Information

Carrie Bailey

Brief Summary


Primary Objective 
• To evaluate the long-term efficacy of Kuvan in preserving neurocognitive function in children with PKU when treatment is initiated at 0-6 years  
Secondary Objectives  
• To evaluate the long-term safety of Kuvan in the study population
• To evaluate the effect of Kuvan on growth parameters in the study population
Substudy 1: 6-Month Safety and Efficacy in Children 0-6 Years Old 
Primary Objective 
• To evaluate the safety of 6 months of treatment with Kuvan in children with PKU who are 0-6 years old.  
Secondary Objective  
• To evaluate the efficacy of 6 months of treatment with Kuvan in controlling blood Phe concentration within acceptable ranges in children with PKU who are 0-6 years old  
• To evaluate baseline neurocognitive function for all Kuvan-responsive subjects and 6-month Bayley-III data for subjects who are 0-2 years old at enrollment 
Substudy 2: Population Pharmacokinetics in Children 0-6 Years Old 
Primary Objective
• To evaluate the population pharmacokinetics of Kuvan in young children


Inclusion Criteria

• Established diagnosis of PKU with hyperphenylalaninemia (HPA) documented in the medical record by at least 2 blood Phe concentrations ≥ 360 μmol/L (6 mg/dL) taken at least 3 days apart
• Documented blood Phe control (defined by the standard used at each treatment center) prior to study enrollment, if applicable (eg, the subject is old enough for these data to be collected); blood Phe concentrations for subjects < 6 months old at Screening must be considered controlled and stable by the Investigator
• Willing to adhere to a prescribed Phe-restricted diet in order to maintain blood Phe concentrations within the recommended ranges established at the subject’s study site
• Age 0 to 6 years old, inclusive, at Screening
• Parent(s) or guardian(s) 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
• Parent(s) or guardian(s) willing and able to comply with all study procedures
• Female subjects of childbearing potential (as determined by the investigator) and sexually mature male subjects willing to use a medically accepted method of contraception throughout tests during the course of the study

Individuals eligible to participate in Part 2: Neurocognitive Study and Substudy 1 must meet both of the following criteria:
• Completion of Week 4 visit in Part 1
• Responsive to Kuvan during Part 1, defined as a ≥ 30% average reduction in blood Phe concentration calculated as the mean of the weekly percent change from baseline in blood Phe concentration at Weeks 1, 2, 3, and 4
• Bayley-III or IQ test score ≥ 80 within 6 weeks of determination of Kuvan responsiveness


Exclusion Criteria

• Established diagnosis of primary tetrahydrobiopterin (BH4) deficiency
• Known hypersensitivity to Kuvan or its excipients
• History of organ transplantation
• Perceived to be unreliable or unavailable for study participation or to have parents or legal guardians who are perceived to be unreliable or unavailable
• Use of methotrexate or other medications that inhibit folate metabolism
• Serious neuropsychiatric illness (eg, major depression) not currently under medical control
• Use of Kuvan or any investigational agent within 30 days prior to Screening, or known requirement for any investigational agent prior to completion of all scheduled study assessments
• Concurrent disease or condition that would interfere with study participation or safety (eg, seizure disorder, oral steroid-dependent asthma or other condition requiring oral or parenteral corticosteroid administration, or insulin-dependent diabetes)
• Any condition that, in the view of the Principal Investigator (PI), renders the subject at high risk for failure to comply with treatment or to complete the study