kuvan®'s effect on the cognition of children with phenylketonuria

Conditions: Phenylketonuria

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.


Eligibility 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

Keywords: phenylketonuria kuvan sapropterin dihydrochloride