NCT01965912

Brief 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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
34

participants targeted

Target at below P25 for phase_4

Timeline
Completed

Started Oct 2013

Longer than P75 for phase_4

Geographic Reach
4 countries

12 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

October 1, 2013

Completed
15 days until next milestone

First Submitted

Initial submission to the registry

October 16, 2013

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 18, 2013

Completed
9.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 4, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 4, 2023

Completed
Last Updated

April 24, 2023

Status Verified

March 1, 2023

Enrollment Period

9.3 years

First QC Date

October 16, 2013

Last Update Submit

April 21, 2023

Conditions

Phenylketonuria

Keywords

PhenylketonuriaKuvanSapropterin dihydrochloride

Outcome Measures

Primary Outcomes (1)

  • Mean Full Scale Intelligence Quotient (FSIQ) Score of the Wechsler Intelligence Scale for Children (WISC)-IV

    Year 7

Secondary Outcomes (12)

  • Height compared to the World Health Organization (WHO) Growth Standards

    up to 7 years

  • Weight compared to the World Health Organization (WHO) Growth Standards

    up to 7 years

  • Blood levels of tyrosine, tryptophan, pre-albumin and methylmalonic acid

    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

    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

    up to 7 years

  • +7 more secondary outcomes

Study Arms (1)

Kuvan®

EXPERIMENTAL
Drug: Kuvan®

Interventions

Kuvan®DRUG

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).

Also known as: Sapropterin dihydrochloride
Kuvan®

Eligibility Criteria

Age4 Years - 5 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (12)

Research site

Munich, Germany

Location

Research site

Münster, Germany

Location

Research site

Bologna, Italy

Location

Research site - Bambino Gesu

Roma, Italy

Location

Research site - La Sapienza

Roma, Italy

Location

Research Site

Barcelona, Spain

Location

Research site

Murcia, Spain

Location

Research site

Santiago de Compostela, Spain

Location

Research site

Birmingham, United Kingdom

Location

Research site

Bristol, United Kingdom

Location

Research Site - Evelina

London, United Kingdom

Location

Research site - GOSH

London, United Kingdom

Location

MeSH Terms

Conditions

Phenylketonurias

Interventions

sapropterin

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, InbornBrain Diseases, MetabolicBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesAmino Acid Metabolism, Inborn ErrorsMetabolism, Inborn ErrorsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMetabolic DiseasesNutritional and Metabolic Diseases

Study Officials

  • Ece Kucuksayrac, MD

    BioMarin Pharmaceutical

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 16, 2013

First Posted

October 18, 2013

Study Start

October 1, 2013

Primary Completion

January 4, 2023

Study Completion

January 4, 2023

Last Updated

April 24, 2023

Record last verified: 2023-03

Locations

IT(3)GB(4)DE(2)ES(3)