Study of Long-Term Neurocognitive Outcomes in Children with Phenylketonuria Treated with Sepiapterin

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What is this study about?

This study is evaluating sepiapterin as a treatment for children with phenylketonuria (PKU). Phenylketonuria is an inherited disorder that increases levels of a substance called phenylalanine in the blood. If left untreated, high phenylalanine levels can damage the brain and cause severe intellectual disability. The purpose of this research is to evaluate how well sepiapterin preserves brain function in children with PKU when treatment begins early in childhood.

The study will follow children under 10 years of age over a period of several years to measure changes in their thinking abilities and intelligence. Researchers will use age-appropriate intelligence tests to track how children’s cognitive abilities develop while receiving sepiapterin treatment. During the study, children will continue their prescribed diet that controls protein and phenylalanine intake.

The research will also track quality of life measures and blood phenylalanine levels over time. This long-term follow-up will help determine if sepiapterin can provide lasting protection for brain development in children with PKU.

1 Initial Participation

After joining the study, you will begin an open-label clinical trial testing a medication called sepiapterin (PTC923), which is a powder for oral use intended to treat phenylketonuria (PKU).

This study aims to evaluate how sepiapterin helps preserve brain function when treatment starts in early childhood. You will be monitored for up to 4 years during this trial.

2 Medication Administration

You will receive sepiapterin (PTC923) in powder form for oral use throughout the study period.

You must maintain your prescribed daily protein and phenylalanine (Phe) intake during the screening period and initial part of the study.

Specific dosage and frequency of sepiapterin administration will be provided by your study doctor.

3 Blood Tests

Your phenylalanine (Phe) levels will be regularly monitored through blood tests throughout the study.

These tests will track how your Phe levels change over time with treatment.

4 Cognitive Testing

You will undergo intelligence testing using standardized tests appropriate for your age:

If you are between 30 months and 6 years old, you’ll take the WPPSI-IV (Wechsler Preschool and Primary Scale of Intelligence).

If you are 6 years or older, you’ll take the WISC-V (Wechsler Intelligence Scale for Children).

These tests will be conducted at the start of the study and then periodically to measure changes in your cognitive function over the 2-year and 4-year periods.

5 Quality of Life Assessments

You will complete quality of life questionnaires throughout the study period:

The PKU-QOL (Phenylketonuria Quality of Life) questionnaire specifically addresses how PKU affects your daily life.

The EQ-5D (European Quality of Life – 5 Dimensions) questionnaire measures general health status.

6 Long-Term Follow-up

You will continue with regular study visits for up to 4 years.

These visits will include the cognitive tests and quality of life assessments mentioned above.

The study is scheduled to run until July 2032, with primary completion expected by July 2025.

7 Contraception Requirements

If applicable, you must follow the contraception requirements throughout the study and for 90 days after your last dose:

Women who can become pregnant must use highly effective contraception (with failure rate <1% per year) or practice abstinence.

Sexually active males with female partners who can become pregnant must use barrier contraception unless they’ve had a vasectomy at least 16 weeks prior.

Males must also refrain from sperm donations during the study and for 90 days after the last dose.

Who Can Join the Study?

You must sign informed consent, and children must give assent (agreement) if able, with parent/legal representative consent.
You must be under 10 years of age when signing the consent form.
Your parent(s) or legal representative(s) must be willing and able to follow all study procedures.
You must be an outpatient (not hospitalized).
You must have a diagnosis of phenylketonuria (PKU) with at least 2 blood phenylalanine (Phe) measurements of 600 μmol/L or higher in your medical history. Phe is an amino acid that builds up in the blood of people with PKU.
You must be willing to maintain your prescribed daily protein/Phe diet during screening and the first part of the study.
If you are 1 month or older at screening: You must have at least one documented blood Phe measurement below 480 μmol/L within 1 month before screening.
If you are 1 month or older at screening: You must have two screening blood Phe concentration values between 120 and 480 μmol/L.
If you are less than 1 month old when consenting: Your blood Phe at newborn screening must be 600 μmol/L or higher.
If you are between 30 months and 10 years old: Your baseline Full Scale Intelligence Quotient (FSIQ) score must be 80 or higher.
Women who can become pregnant must have a negative pregnancy test at screening and use effective birth control or abstinence during the study and for 90 days after the last dose.
Sexually active males must use barrier birth control during the study and for 90 days after the last dose, unless they’ve had a vasectomy (at least 16 weeks post-procedure).

Who Cannot Join the Study?

You cannot join if you have a known hypersensitivity (allergic reaction) to sepiapterin or any of its ingredients.
You cannot participate if you have any other medical conditions that, in the opinion of the investigators, might interfere with study participation.
You cannot be in the study if you are currently participating in another clinical trial with an investigational drug.
You cannot join if you have severe liver dysfunction (problems with how your liver works).
You cannot participate if you have severe kidney dysfunction (problems with how your kidneys work).
You cannot be included if you have a history of non-compliance (not following) with medical treatment or dietary restrictions.
You cannot join if you have a cognitive impairment (difficulty with thinking, learning, memory) that would prevent understanding of the study procedures.
You cannot participate if your parents or legal guardians are unable to provide informed consent (permission).
You cannot be in the study if you have previously received sepiapterin treatment.
You cannot join if you have been diagnosed with any neurological disorder (brain or nervous system condition) other than PKU.

Where you can join this trial?

Verified and Recommended Sites

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Verified Sites

Site Name	City	Country
Centre Hospitalier Universitaire De Lille	Lille	France
Pomeranian Medical University	Szczecin	Poland
Hopital Necker Enfants Malades	Paris	France

Other Sites

Site Name	City	Country
Instytut Matki I Dziecka	Warsaw	Poland
Karolinska University Hospital	Solna	Sweden
Children’s Health Ireland	Dublin	Ireland
Cmfmaw Hoijhlfidhz Rmtgxdsn Udebmefulhtyw Dq Tuzes	Tours	France

Trial status

Country	Status	Recruitment Start
France	Recruiting	01.07.2025
Ireland	Recruiting	01.07.2025
Poland	Recruiting	01.07.2025
Sweden	Not yet recruiting	01.07.2025

Trial locations

Investigated drugs:

Sepiapterin

Sepiapterin is a medication being studied for the treatment of phenylketonuria (PKU), which is a rare genetic disorder that affects how the body processes protein. The medication is designed to help the body convert phenylalanine (an amino acid found in protein) into tyrosine, potentially reducing the harmful buildup of phenylalanine in the blood and brain that occurs in people with PKU. This study specifically looks at how this medication might help preserve brain function in children with PKU when treatment begins early in childhood.

Investigated diseases:

Phenylketonuria

Phenylketonuria is an inherited metabolic disorder where the body cannot properly break down the amino acid phenylalanine. In this condition, phenylalanine builds up in the blood and other tissues due to a deficiency of the enzyme phenylalanine hydroxylase. Without early dietary intervention, the accumulation of phenylalanine can lead to intellectual disability, delayed development, behavioral problems, and seizures. Infants with phenylketonuria appear normal at birth but begin to show symptoms within the first few months of life if the condition remains untreated. The disease affects the brain’s development and function, particularly during the crucial early years of brain development. Phenylketonuria is typically detected through newborn screening programs in many countries.

Trial ID:

2024-514435-20-00

Protocol code:

PTC923-PKU-401

Trial Phase:

Therapeutic confirmatory (Phase III)

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Study of Long-Term Neurocognitive Outcomes in Children with Phenylketonuria Treated with Sepiapterin

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