Kuvan®'s Effect on the Cognition of Children With Phenylketonuria

• Register: ClinicalTrials.gov
• Last refreshed on: 1 May 2023
• Main ID: NCT01965912
• Date of registration: 16/10/2013
• Prospective Registration: No
• Primary sponsor: BioMarin Pharmaceutical
• Public title: Kuvan®'s Effect on the Cognition of Children With Phenylketonuria KOGNITO
• Scientific 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
• Date of first enrolment: October 2013
• Target sample size: 34
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01965912
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 4

Countries of recruitment

Germany, Italy, Spain, United Kingdom

Contacts

• Name: Ece Kucuksayrac, MD
• Affiliation: BioMarin Pharmaceutical

Key inclusion & exclusion criteria

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



Age minimum: 4 Years
Age maximum: 5 Years
Gender: All

Health Condition(s) or Problem(s) studied

Phenylketonuria

Intervention(s)

Drug: Kuvan®

Primary Outcome(s)

Mean Full Scale Intelligence Quotient (FSIQ) Score of the Wechsler Intelligence Scale for Children (WISC)-IV [Time Frame: Year 7]

Secondary Outcome(s)

Index of Dietary Control (IDC) [Time Frame: up to 7 years]

Phenylalanine levels [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]

Blood levels of tyrosine, tryptophan, pre-albumin and methylmalonic acid [Time Frame: up to 7 years]

Distribution of phenylalanine hydroxylase (PAH) genotype [Time Frame: Baseline]

Percentage of tablets taken to assess treatment compliance [Time Frame: up to 7 years]

Weight compared to the World Health Organization (WHO) Growth Standards [Time Frame: up to 7 years]

Height compared to the World Health Organization (WHO) Growth Standards [Time Frame: up to 7 years]

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]

Number of subjects with Adverse Events and Serious Adverse Events [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]

Secondary ID(s)

EMR 700773-002

2009-015844-41

Source(s) of Monetary Support

Please refer to primary and secondary sponsors