A Study of the Long-term Effects on Mental Abilities of 4 to 5 Year-old Children with a Disease Caused by an Enzyme Defect (Phenylketonuria) that Have Been Treated with Kuvan® (a Medicinal Product aimed at Restoring the Defect) for 7 Years.

A Phase IV 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. - KOGNITO (Kuvan®’s effect on the cOGNITion of children with phenylketOnuria)

Status

Not yet recruiting

Phases

Phase 4

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2009-015844-41-DE

Enrollment

Registered

2013-06-13

Start date

2013-09-10

Completion date

Unknown

Last updated

2019-06-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Phenylketonuria MedDRA version: 20.0 Level: LLT Classification code 10034873 Term: Phenylketonuria (PKU) System Organ Class: 100000004850

Interventions

Trade Name: Kuvan Pharmaceutical Form: Soluble tablet INN or Proposed INN: SAPROPTERIN CAS Number: 62989-33-7 Other descriptive name: te

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: The target population for this trial is children with confirmed diagnosis of PKU. Inclusion criteria: • Male or female outpatients, 4 to 5 years of age (=4 and =65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: • Known hypersensitivity to Kuvan® or its excipients. • Known hypersensitivity to other approved or non-approved formulations of tetrahydrobiopterin. • 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.

Design outcomes

Primary

Measure	Time frame
Main Objective: The primary objective of this trial is to evaluate the long-term neurocognitive (NC) outcomes in children with hyperphenylalaninemia (HPA) due to phenylketonuria (PKU) treated with Kuvan® and a phenylalanine (Phe)-restricted diet for 7 years.;Secondary Objective: The main secondary objectives of this trial are to evaluate the growth and safety in children with HPA due to PKU treated with Kuvan® and a Phe-restricted diet and followed for a period of 7 years.;Primary end point(s): The primary endpoint will be the mean IQ score of PKU children on diet and treated with Kuvan® after 7 years of treatment in the study.;Timepoint(s) of evaluation of this end point: After 7 years of treatment with Kuvan® in the study.	—

Measure

Time frame

Main Objective: The primary objective of this trial is to evaluate the long-term neurocognitive (NC) outcomes in children with hyperphenylalaninemia (HPA) due to phenylketonuria (PKU) treated with Kuvan® and a phenylalanine (Phe)-restricted diet for 7 years.;Secondary Objective: The main secondary objectives of this trial are to evaluate the growth and safety in children with HPA due to PKU treated with Kuvan® and a Phe-restricted diet and followed for a period of 7 years.;Primary end point(s): The primary endpoint will be the mean IQ score of PKU children on diet and treated with Kuvan® after 7 years of treatment in the study.;Timepoint(s) of evaluation of this end point: After 7 years of treatment with Kuvan® in the study.

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Secondary

Measure	Time frame
Secondary end point(s): • Height and weight compared to the World Health Organization (WHO) Growth Standards at each time point. • Blood levels of tyrosine (Tyr), tryptophan, pre-albumin, and methylmalonic acid compared to age-related norms. • IQ score and subscores at each time-point: - the Verbal IQ, the Performance IQ and the Full Scale IQ (FSIQ) of the WPPSI™-III at baseline; - the Verbal Comprehension, the Perceptual Reasoning, the Working Memory, the Processing Speed Indexes and the FSIQ of the WISC®-IV at post-baseline time-points. • Change from baseline in FSIQ score at 2, 4 and 7 years. • Dietary Phe tolerance over the 7 year period, as represented by mean Phe prescription (in mg/day and mg/kg/day) quarterly and mean Phe intake (in mg/day) bi-annually. • Monthly Phe levels and Phe levels on the day of the IQ test. • IDC (Index of Dietary Control = half-year Phe level medians averaged from baseline to 2, 4 and 7 years). • Adherence to treatment (diet+Kuvan®) as assessed by the percentage of monthly Phe levels within target blood Phe concentration during Study Period and adherence to Kuvan® treatment as assessed by percentage of tablets taken. • Frequencies and distributions of phenylalanine hydroxylase (PAH) genotype and relationships with response to Kuvan®/BH4. • Safety (extent of exposure to Kuvan®; nature, incidence, and severity of adverse events (AEs)/serious adverse events (SAEs), including relationship to trial treatment, AEs/SAEs leading to dose modification or discontinuation of trial treatment; changes and abnormalities in vital signs and safety laboratory parameters; physical examination; use of concomitant medications). ;Timepoint(s) of evaluation of this end point: After 7 years of treatment with Kuvan® in the study.	—

Measure

Time frame

Secondary end point(s): • Height and weight compared to the World Health Organization (WHO) Growth Standards at each time point. • Blood levels of tyrosine (Tyr), tryptophan, pre-albumin, and methylmalonic acid compared to age-related norms. • IQ score and subscores at each time-point: - the Verbal IQ, the Performance IQ and the Full Scale IQ (FSIQ) of the WPPSI™-III at baseline; - the Verbal Comprehension, the Perceptual Reasoning, the Working Memory, the Processing Speed Indexes and the FSIQ of the WISC®-IV at post-baseline time-points. • Change from baseline in FSIQ score at 2, 4 and 7 years. • Dietary Phe tolerance over the 7 year period, as represented by mean Phe prescription (in mg/day and mg/kg/day) quarterly and mean Phe intake (in mg/day) bi-annually. • Monthly Phe levels and Phe levels on the day of the IQ test. • IDC (Index of Dietary Control = half-year Phe level medians averaged from baseline to 2, 4 and 7 years). • Adherence to treatment (diet+Kuvan®) as assessed by the percentage of monthly Phe levels within target blood Phe concentration during Study Period and adherence to Kuvan® treatment as assessed by percentage of tablets taken. • Frequencies and distributions of phenylalanine hydroxylase (PAH) genotype and relationships with response to Kuvan®/BH4. • Safety (extent of exposure to Kuvan®; nature, incidence, and severity of adverse events (AEs)/serious adverse events (SAEs), including relationship to trial treatment, AEs/SAEs leading to dose modification or discontinuation of trial treatment; changes and abnormalities in vital signs and safety laboratory parameters; physical examination; use of concomitant medications). ;Timepoint(s) of evaluation of this end point: After 7 years of treatment with Kuvan® in the study.

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Countries

Germany, Italy, Spain, United Kingdom

Contacts

Public ContactClinical Trials Information

BioMarin International Ltd.

KOGNITO@bmrn.com

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026