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

Information source: Merck KGaA
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Phenylketonuria

Intervention: Kuvan® (Drug)

Phase: Phase 4

Status: Recruiting

Sponsored by: Merck KGaA

Official(s) and/or principal investigator(s):
Medical Responsible, Study Director, Affiliation: Merck KGaA

Overall contact:
Merck KGaA Communication Center, Phone: +49 6151 72 5200, Email: service@merckgroup.com

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.

Clinical Details

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

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Mean Full Scale Intelligence Quotient (FSIQ) Score of the Wechsler Intelligence Scale for Children (WISC)-IV

Secondary outcome:

Height compared to the World Health Organization (WHO) Growth Standards

Weight compared to the World Health Organization (WHO) Growth Standards

Blood levels of tyrosine, tryptophan, pre-albumin and methylmalonic acid

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

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

Change from Baseline in FSIQ score at 2, 4 and 7 years

Dietary Phenylalanine tolerance

Phenylalanine levels

Index of Dietary Control (IDC)

Percentage of tablets taken to assess treatment compliance

Distribution of phenylalanine hydroxylase (PAH) genotype

Number of subjects with Adverse Events and Serious Adverse Events

Eligibility

Minimum age: 4 Years. Maximum age: 5 Years. Gender(s): Both.

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

Locations and Contacts

Merck KGaA Communication Center, Phone: +49 6151 72 5200, Email: service@merckgroup.com

Research Site, Düsseldorf, Germany; Recruiting

Research site, Munich, Germany; Not yet recruiting

Research site, Münster, Germany; Recruiting

Research site, Bologna, Italy; Recruiting

Research site, Milano, Italy; Recruiting

Research site, Padova, Italy; Recruiting

Research site, Rome, Italy; Recruiting

Research site, Baracaldo Bilbao, Spain; Recruiting

Research Site, Barcelona, Spain; Recruiting

Research site, Murcia, Spain; Not yet recruiting

Research site, Santiago de Compostela, Spain; Recruiting

Research site, Birmingham, United Kingdom; Recruiting

Research site, Bristol, United Kingdom; Recruiting

Research site, London, United Kingdom; Recruiting

Additional Information

Starting date: October 2013
Last updated: August 11, 2015

Page last updated: August 23, 2015

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