Overview

This trial is active, not recruiting.

Condition phenylketonuria
Treatment kuvan®
Phase phase 4
Sponsor BioMarin Pharmaceutical
Start date October 2013
End date November 2022
Trial size 34 participants
Trial identifier NCT01965912, 2009-015844-41, EMR 700773-002

Summary

The study is a single-cohort, interventional, open-label trial to evaluate long-term neurocognitive (NC) outcomes in children aged 4 to 5 years with phenylketonuria (PKU) treated with Kuvan® and Phenylalanine-restricted diet over a period of 7 years.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
kuvan® Sapropterin dihydrochloride
Kuvan® oral soluble tablet will be administered once daily along with Phenylalanine-restricted diet for a period of 7 years. Dosage of Kuvan® could range from 5 to 20 milligram per kilogram per day (mg/kg/day), as per Summary of Product Characteristics (SPC).

Primary Outcomes

Measure
Mean Full Scale Intelligence Quotient (FSIQ) Score of the Wechsler Intelligence Scale for Children (WISC)-IV
time frame: Year 7

Secondary Outcomes

Measure
Height compared to the World Health Organization (WHO) Growth Standards
time frame: up to 7 years
Weight compared to the World Health Organization (WHO) Growth Standards
time frame: up to 7 years
Blood levels of tyrosine, tryptophan, pre-albumin and methylmalonic acid
time frame: up to 7 years
Intelligence Quotient (IQ) score and sub-scores such as, verbal IQ, performance IQ, Full Scale Intelligence Quotient (FSIQ) of Wechsler Preschool and Primary Scale of Intelligence (WPPSI)-III
time frame: Baseline
Intelligence Quotient (IQ) score and sub-scores such as verbal comprehension, perceptual reasoning, working memory, and processing speed indexes and Full Scale Intelligence Quotient (FSIQ) of the Wechsler Intelligence Scale for Children (WISC)-IV
time frame: up to 7 years
Change from Baseline in FSIQ score at 2, 4 and 7 years
time frame: Baseline, and Year 2, 4 and 7
Dietary Phenylalanine tolerance
time frame: up to 7 years
Phenylalanine levels
time frame: up to 7 years
Index of Dietary Control (IDC)
time frame: up to 7 years
Percentage of tablets taken to assess treatment compliance
time frame: up to 7 years
Distribution of phenylalanine hydroxylase (PAH) genotype
time frame: Baseline
Number of subjects with Adverse Events and Serious Adverse Events
time frame: up to 7 years

Eligibility Criteria

Male or female participants from 4 years up to 5 years old.

Inclusion Criteria: - Male or female outpatients, 4 to 5 years of age (greater than or equal to 4 and less than 6) at the time of informed consent form signature by parent(s) or guardian(s) - Confirmed clinical and biochemical diagnosis of PKU, including at least two separate blood phenylalanine levels greater than or equal to 400 micromole per liter (mcmol/L) - Defined pre-Kuvan®/-tetrahydrobiopterin (BH4) dietary phenylalanine tolerance consistent with the diagnosis of PKU - Responsive to Kuvan®/BH4: - For subjects currently treated with Kuvan®/BH4 at Screening: subject is a responder as per Investigator judgment based on documented effect of Kuvan®/BH4 on phenylalanine levels and/or phenylalanine tolerance - For subjects not treated with Kuvan®/BH4 at Screening: a response test has been performed during Screening or is available from the subject's medical records and satisfies the 3 following criteria: a decrease in blood phenylalanine levels of at least 30 percent was observed after at least 24 hours with a dose of at least 10 mg/kg/day - Intelligence Quotient (IQ) greater than or equal to 70, as assessed with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI)-III, 2nd part - Good adherence with dietary treatment (including prescribed dietary phenylalanine restriction and prescribed amounts of phenylalanine-free protein supplements and low-phenylalanine foods), as assessed by the Investigator - Well-controlled phenylalanine levels, as assessed by a minimum of 75 percent of phenylalanine levels within the target recommended in each centre during the previous 3 months - Low phenylalanine diet started within the first 3 weeks of life - Parent(s) or guardian(s) willing to comply with all study procedures, maintain strict adherence with the diet, and willing and able to provide written, signed informed consent before any trial-related activities are carried out, as well as ability of child to comply with trial procedures Exclusion Criteria: - Known hypersensitivity to Kuvan® or its excipients - Known hypersensitivity to other approved or non-approved formulations of BH4 - Previous diagnosis of BH4 deficiency - Current use of methotrexate, trimethoprim or other dihydrofolate reductase inhibitors - Current use of medications that are known to affect nitric oxide synthesis, metabolism or action - Current use of experimental or unregistered drugs (other than sapropterin/BH4) that may affect the study outcomes or use of such agents within 30 days prior to Screening - Concurrent use of levodopa - Concurrent disease or condition that would induce repeatedly catabolic situations, or interfere with the trial participation, diet, or NC development, as assessed by the Investigator - Any condition that, in the view of the Investigator, renders the subject at high risk for failure to comply with treatment or to complete the trial - Participation in a clinical trial investigating any other agent than Kuvan® within the past 30 days

Additional Information

Official title A Phase 4 Open-Label, Single-Cohort Study of the Long-Term Neurocognitive Outcomes in 4 to 5 Year-Old Children With Phenylketonuria Treated With Sapropterin Dihydrochloride (Kuvan®) for 7 Years
Trial information was received from ClinicalTrials.gov and was last updated in May 2016.
Information provided to ClinicalTrials.gov by BioMarin Pharmaceutical.