Phenylketonuria Clinical Trial
— KOGNITOOfficial 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
Verified date | March 2023 |
Source | BioMarin Pharmaceutical |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 34 |
Est. completion date | January 4, 2023 |
Est. primary completion date | January 4, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 4 Years to 5 Years |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
Germany | Research site | Munich | |
Germany | Research site | Münster | |
Italy | Research site | Bologna | |
Italy | Research site - Bambino Gesu | Roma | |
Italy | Research site - La Sapienza | Roma | |
Spain | Research Site | Barcelona | |
Spain | Research site | Murcia | |
Spain | Research site | Santiago de Compostela | |
United Kingdom | Research site | Birmingham | |
United Kingdom | Research site | Bristol | |
United Kingdom | Research Site - Evelina | London | |
United Kingdom | Research site - GOSH | London |
Lead Sponsor | Collaborator |
---|---|
BioMarin Pharmaceutical |
Germany, Italy, Spain, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Mean Full Scale Intelligence Quotient (FSIQ) Score of the Wechsler Intelligence Scale for Children (WISC)-IV | Year 7 | ||
Secondary | Height compared to the World Health Organization (WHO) Growth Standards | up to 7 years | ||
Secondary | Weight compared to the World Health Organization (WHO) Growth Standards | up to 7 years | ||
Secondary | Blood levels of tyrosine, tryptophan, pre-albumin and methylmalonic acid | up to 7 years | ||
Secondary | 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 | Baseline | ||
Secondary | 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 | up to 7 years | ||
Secondary | Change from Baseline in FSIQ score at 2, 4 and 7 years | Baseline, and Year 2, 4 and 7 | ||
Secondary | Dietary Phenylalanine tolerance | up to 7 years | ||
Secondary | Phenylalanine levels | up to 7 years | ||
Secondary | Index of Dietary Control (IDC) | up to 7 years | ||
Secondary | Percentage of tablets taken to assess treatment compliance | up to 7 years | ||
Secondary | Distribution of phenylalanine hydroxylase (PAH) genotype | Baseline | ||
Secondary | Number of subjects with Adverse Events and Serious Adverse Events | up to 7 years |
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