PhenylketonuriaPhase 4KOGNITONCT01965912
Kuvan®'s Effect on the Cognition of Children With Phenylketonuria
A Phase 4 study testing Kuvan® in people with Phenylketonuria, run by BioMarin Pharmaceutical at 12 sites in 4 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 4 to 5 years
- Conditions the study is for
- Phenylketonuria
- What is being tested?
- Kuvan®
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 12 sitesin 4 countries
- Study dates
- Oct 2013to 4 Jan 2023
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 5 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
12 sites in 4 countries.
12 sites in 4 countries
United Kingdom4 sites
Research site
Birmingham
Research site
Bristol
Research Site - Evelina
London
Research site - GOSH
London
Italy3 sites
Research site
Bologna
Research site - Bambino Gesu
Roma
Research site - La Sapienza
Roma
Spain3 sites
Research Site
Barcelona
Research site
Murcia
Research site
Santiago de Compostela
About this study
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
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.
- Conditions
- Phenylketonuria
- Being tested
- Kuvan®
- Keywords
- Phenylketonuria, Kuvan, Sapropterin dihydrochloride
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Kuvan®Drug
Also called Sapropterin dihydrochloride
Kuvan® oral soluble tablet will be administered once daily along with Phenylalanine-restricted diet for a period of 7 years. Dosage of Kuvan® could range from 5 to 20 milligram per kilogram per day (mg/kg/day), as per Summary of Product Characteristics (SPC).
| Study group | Role | What they receive |
|---|---|---|
| Kuvan® | Experimental | Not described Receives: Drug: Kuvan® |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Full Scale Intelligence Quotient (FSIQ) Score of the Wechsler Intelligence Scale for Children (WISC)-IV
Measured: Year 7
Secondary outcomes (12)
Height compared to the World Health Organization (WHO) Growth Standards
Measured: up to 7 years
Weight compared to the World Health Organization (WHO) Growth Standards
Measured: up to 7 years
Blood levels of tyrosine, tryptophan, pre-albumin and methylmalonic acid
Measured: up to 7 years
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
Measured: Baseline
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
Measured: up to 7 years
Change from Baseline in FSIQ score at 2, 4 and 7 years
Measured: Baseline, and Year 2, 4 and 7
Dietary Phenylalanine tolerance
Measured: up to 7 years
Phenylalanine levels
Measured: up to 7 years
Index of Dietary Control (IDC)
Measured: up to 7 years
Percentage of tablets taken to assess treatment compliance
Measured: up to 7 years
Distribution of phenylalanine hydroxylase (PAH) genotype
Measured: Baseline
Number of subjects with Adverse Events and Serious Adverse Events
Measured: up to 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Oct 2013 (estimated)
- Study startOct 2013
- Primary completion4 Jan 2023
- Study completion4 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PhenylketonuriaStudies of the same condition, open and under way.
- More trials run by BioMarin PharmaceuticalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioMarin Pharmaceutical
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Ece Kucuksayrac, MD, Study director, BioMarin Pharmaceutical
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01965912
- Sponsor's protocol ID
- EMR 700773-002
- Other IDs
- 2009-015844-41, 2009
- Acronym
- KOGNITO
- Status last verified
- Mar 2023
- First submitted
- 16 Oct 2013
- Last updated
- 24 Apr 2023
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01965912
- Acronym / sponsor ID
- KOGNITO / EMR 700773-002
- Conditions
- Phenylketonuria
- Keywords
- Phenylketonuria, Kuvan, Sapropterin dihydrochloride
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- BioMarin PharmaceuticalIndustry (pharma, biotech, devices)
- Study start
- Oct 2013
- Primary completion
- 4 Jan 2023 (actual)
- Study completion
- 4 Jan 2023 (actual)
- First posted
- 18 Oct 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Kuvan® | Experimental | Drug: Kuvan® |
Who may qualify
- Ages
- 4 to 5 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (11 listed)
- 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:
- Intelligence Quotient (IQ) greater than or equal to 70, as assessed with the Wechsler Preschool and Primary Scale of Intelligence (WPPSI)-III, 2nd part
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Kuvan®Also: Sapropterin dihydrochlorideKuvan® oral soluble tablet will be administered once daily along with Phenylalanine-restricted diet for a period of 7 years. Dosage of Kuvan® could range from 5 to 20 milligram per kilogram per day (mg/kg/day), as per Summary of Product Characteristics (SPC). | Drug | Kuvan® |
Primary outcome
Mean Full Scale Intelligence Quotient (FSIQ) Score of the Wechsler Intelligence Scale for Children (WISC)-IV
Time frame: Year 7
12 secondary outcomes
Height compared to the World Health Organization (WHO) Growth Standards
Time frame: up to 7 years
Weight compared to the World Health Organization (WHO) Growth Standards
Time frame: up to 7 years
Blood levels of tyrosine, tryptophan, pre-albumin and methylmalonic acid
Time frame: up to 7 years
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
Time frame: Baseline
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
Time frame: up to 7 years
Change from Baseline in FSIQ score at 2, 4 and 7 years
Time frame: Baseline, and Year 2, 4 and 7
Dietary Phenylalanine tolerance
Time frame: up to 7 years
Phenylalanine levels
Time frame: up to 7 years
Index of Dietary Control (IDC)
Time frame: up to 7 years
Percentage of tablets taken to assess treatment compliance
Time frame: up to 7 years
Distribution of phenylalanine hydroxylase (PAH) genotype
Time frame: Baseline
Number of subjects with Adverse Events and Serious Adverse Events
Time frame: up to 7 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ece Kucuksayrac, MD study director
BioMarin Pharmaceutical
12 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Kuvan® in people with Phenylketonuria, run by BioMarin Pharmaceutical at 12 sites in 4 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United Kingdom, Italy, Spain, Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Full Scale Intelligence Quotient (FSIQ) Score of the Wechsler Intelligence Scale for Children (WISC)-IV (time frame: Year 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2023.