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

BioMarin Pharmaceutical

Status and phase

Completed

Phase 4

Conditions

Phenylketonuria

Treatments

Drug: Kuvan®

Study type

Interventional

Funder types

Industry

Identifiers

NCT01965912

2009-015844-41 (EudraCT Number)

EMR 700773-002

Details and patient eligibility

About

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.

Enrollment

34 patients

Sex

All

Ages

4 to 5 years old

Volunteers

No Healthy Volunteers

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