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.
- Conditions
- PhenylketonuriaMedDRA version: 16.1Level: LLTClassification code 10034873Term: Phenylketonuria (PKU)System Organ Class: 100000004850Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
- Registration Number
- EUCTR2009-015844-41-ES
- Lead Sponsor
- Merck KGaA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Not Recruiting
- Sex
- All
- Target Recruitment
- 30
The target population for this trial is children with confirmed diagnosis of PKU.
- Male or female outpatients, 4 to 5 years of age (>or=4 and <6) at the time of ICF signature by parent(s) or guardian(s).
- Confirmed clinical and biochemical diagnosis of PKU, including at least two separate blood Phe levels >or=400 micromol/L.
- Defined pre-Kuvan®/-tetrahydrobiopterin (BH4) dietary Phe 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 Phe levels and/or Phe tolerance.
- For subjects not treated with Kuvan®/BH4 at Screening: a response test has been performed during Screening or is available from the patient's medical records and satisfies the 3 following criteria: a decrease in blood Phe levels of at least 30% was observed after at least 24 hours with a dose of at least 10 mg/kg/day.
- IQ >or=70, as assessed with the WPPSITM-III 2nd part.
Note: If a subject has undertaken the same test up to 3 months before Screening as part of his/her clinical follow-up, the score can be recorded and the test doesn't need to be repeated.
- Good adherence with dietary treatment (including prescribed dietary Phe restriction and prescribed amounts of Phe-free protein supplements and low-Phe foods), as assessed by the Investigator.
- Well-controlled Phe levels, as assessed by a minimum of 75% of Phe levels within the target recommended in each centre during the previous 3 months.
- Low Phe 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.
Are the trial subjects under 18? yes
Number of subjects for this age range: 30
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
- 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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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.
- Secondary Outcome Measures
Name Time Method