Who may be eligible for the A Study of Sepiapterin in Participants With Phenylketonuria (PKU) trial?

Key Inclusion Criteria: For all participants: * Women of childbearing potential must have a negative pregnancy test at Screening and agree to abstinence or the use of at least one highly effective form of contraception for the duration of the study, and for at least 90 days after the last dose of the study drug. * Willing to maintain prescribed daily protein/Phe during Screening and Part 1. For participants ≥1 month of age at Screening: * Established diagnosis of PKU with hyperphenylalaninemia (HPA) evidenced by at least 2 blood Phe measurement ≥600 micromoles (μmol)/liter (L) as documented in the medical history. * A minimum of 1 documented blood Phe measurement \<480 μmol/L within 1 month prior to Screening. * Two screening blood Phe concentration values must be in the range ≥120 to ≤480 μmol/L. For participants \<1 month of age at the time of informed consent/assent only: * Blood Phe at newborn screening ≥600 μmol/L. For participants ≥30 months to \<10 years of age: * Baseline FSIQ score ≥80. Key Exclusion Criteria: * History of allergies or adverse reactions to any of the ingredients or excipients of synthetic tetrahydrobiopterin (BH4) or sepiapterin. * Serious neuropsychiatric illness (for example, major depression) not currently under medical control or other concurrent disease or condition that, in the opinion of the investigator or sponsor, would interfere with the participant's ability to participate in the study or increase the risk of participation for that participant. * Treatment with BH4 supplementation (sapropterin, Kuvan®) within 3 months prior to Screening. * Current participation in another investigational drug study or use of any investigational agent within 30 days prior to Screening. * Confirmed diagnosis of a primary BH4 deficiency as evidenced by biallelic pathogenic mutations in 6-pyruvoyltetrahydropterin synthase, recessive Guanosine-5'-triphosphate (GTP) cyclohydrolase I, sepiapterin reductase, quinoid dihydropteridine reductase, or pterin 4-alphacarbinolamine dehydratase genes. * Any clinically significant laboratory abnormality as determined by the investigator. * Any past medical history of an abnormal physical examination and/or laboratory findings indicative of signs or symptoms of renal disease, including calculated (Bedside Schwartz Equation) glomerular filtration rate (GFR) \ 6 weeks with sepiapterin (that is, Sephience). Note: Other protocol-defined inclusion and exclusion criteria may apply.

ClinicalTrials.gov record NCT06302348

A Study of Sepiapterin in Participants With Phenylketonuria (PKU)

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Sep 6, 2026

A Phase 3b Open-Label Study of Long-Term Neurocognitive Outcomes in Children With Phenylketonuria Treated With Sepiapterin

About this page. This page shows the study's official ClinicalTrials.gov record ↗, with added help to make it easier to understand. We explain medical terms, highlight key details in plain language, and suggest questions you may want to ask the study team.

The record is periodically copied from ClinicalTrials.gov and may lag behind changes. AI summaries are checked by software, not a clinician.Read moreShow less

The official record is written by the study sponsor and published on ClinicalTrials.gov. It may not always reflect the latest changes. Before making any decisions, please confirm important information with the study team and your own healthcare team.

Where you see "AI summary", AI was used to create a plain-language explanation and software checked it against the source. It has not been reviewed by a clinician, so it may contain mistakes or leave out important details.

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.

Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.

PhasePhase 3A later-stage study, usually with more participants, designed to give stronger evidence about how well a treatment works and how safe it is. It often compares the treatment with standard care or a placebo, and results may support an application for approval.

AgeUp to 9 years old

SexAll

LocationAustralia, France, Ireland, Poland, United Kingdom, United States

AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This Phase 3, open-label study evaluates sepiapterin in children with phenylketonuria (PKU). It begins with an open-label responsiveness test (Part 1) followed by an open-label treatment period (Part 2) during which participants receive age- and weight-adjusted oral sepiapterin once daily for up to 6 years. Key measures include IQ tests, quality-of-life questionnaires, and blood phenylalanine levels.

What it is studying. The study tests the long-term effects of sepiapterin on preserving neurocognitive functioning when started in early childhood in people with PKU. It will track changes in IQ scores, quality-of-life measures, and blood phenylalanine over time.

What the researchers hope to learn. Scientific goals are to evaluate the long-term effect of sepiapterin on neurocognitive outcomes in children with PKU and to measure changes in IQ, quality of life, and blood phenylalanine levels over time.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

The main purpose of this trial is to evaluate the long-term efficacy of sepiapterin on preserving neurocognitive functioning in children with PKU when treatment is initiated in early childhood.

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Drug: Sepiapterin

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion criteria

For all participants:
Women of childbearing potential must have a negative pregnancy test at Screening and agree to abstinence or the use of at least one highly effective form of contraception for the duration of the study, and for at least 90 days after the last dose of the study drug.
Willing to maintain prescribed daily protein/Phe during Screening and Part 1.
For participants ≥1 month of age at Screening:
Established diagnosis of PKU with hyperphenylalaninemia (HPA) evidenced by at least 2 blood Phe measurement ≥600 micromoles (μmol)/liter (L) as documented in the medical history.
A minimum of 1 documented blood Phe measurement <480 μmol/L within 1 month prior to Screening.
Two screening blood Phe concentration values must be in the range ≥120 to ≤480 μmol/L.
For participants <1 month of age at the time of informed consent/assent only:
Blood Phe at newborn screening ≥600 μmol/L.
For participants ≥30 months to <10 years of age:
Baseline FSIQ score ≥80.
Key

Exclusion criteria

History of allergies or adverse reactions to any of the ingredients or excipients of synthetic tetrahydrobiopterin (BH4) or sepiapterin.
Serious neuropsychiatric illness (for example, major depression) not currently under medical control or other concurrent disease or condition that, in the opinion of the investigator or sponsor, would interfere with the participant's ability to participate in the study or increase the risk of participation for that participant.
Treatment with BH4 supplementation (sapropterin, Kuvan®) within 3 months prior to Screening.
Current participation in another investigational drug study or use of any investigational agent within 30 days prior to Screening.
Confirmed diagnosis of a primary BH4 deficiency as evidenced by biallelic pathogenic mutations in 6-pyruvoyltetrahydropterin synthase, recessive Guanosine-5'-triphosphate (GTP) cyclohydrolase I, sepiapterin reductase, quinoid dihydropteridine reductase, or pterin 4-alphacarbinolamine dehydratase genes.
Any clinically significant laboratory abnormality as determined by the investigator.
Any past medical history of an abnormal physical examination and/or laboratory findings indicative of signs or symptoms of renal disease, including calculated (Bedside Schwartz Equation) glomerular filtration rate (GFR) <60 milliliters (mL)/minute (min)/1.73 square meter (m\^2).
Major surgery within 90 days prior to Screening visit.
Previous treatment for >6 weeks with sepiapterin (that is, Sephience).
Note: Other protocol-defined inclusion and exclusion criteria may apply.

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Detailed description from the registry

The study includes 2 parts: Part 1 and 2. Part 1 is an open-label sepiapterin-responsiveness test and Part 2 is an open-label treatment period.

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

The study has two parts: Part 1 is an open‑label sepiapterin‑responsiveness test and Part 2 is an open‑label treatment period in which participants take age‑ and weight‑adjusted sepiapterin orally once daily for up to 6 years. Participants will have neurocognitive testing (FSIQ using WPPSI‑IV or WISC‑V) at baseline and at scheduled follow‑up visits (including Year 2 and Year 4) and will complete quality‑of‑life questionnaires (PKU‑QOL, EQ‑5D) during follow‑up. Blood tests to measure phenylalanine (Phe) levels will be taken at screening and repeatedly during the study (up to 6 years); women of childbearing potential will have a pregnancy test at screening and must agree to contraception requirements. You will be asked to maintain your prescribed daily protein/phenylalanine intake during Screening and Part 1 and to attend regular study visits for assessments and drug dispensing.

How the study is structured. This is an open-label, single-group Phase 3 drug study. Part 1 is an open-label sepiapterin-responsiveness test. Part 2 is an open-label treatment period in which participants take age- and weight-adjusted sepiapterin orally once daily (sepiapterin powder to be mixed in water or apple juice) for up to 6 years. Participants will have scheduled assessments including standardized IQ tests, quality-of-life questionnaires, and blood phenylalanine measurements at specified time points.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

The listed sites are in Australia, France, Ireland, Poland, United Kingdom, United States. Is any of them reachable for me, and does the study help with travel?
Which of the eligibility criteria would need to be checked with tests before I could join?

More on phenylketonuria

Clinical trials38 trials listed for phenylketonuriaEvery trial the registry lists for phenylketonuria, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in phenylketonuria researchLatest monthly update: September 2026. Includes: Diet supply gaps. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start: Mar 4, 2024
Primary completion: Feb 28, 2031 (estimated)
Study completion: Feb 28, 2031 (estimated)
Target enrollment: 56 participants (estimated)
Last updated on registry: Aug 28, 2026
Data verified: Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor: PTC Therapeutics

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Patient Advocacy 📞 1-866-562-4620 ✉ medinfo@ptcbio.com

Participating sites (10)

Filter by country:

Indiana University School of MedicineRecruiting
Indianapolis, Indiana, 46202 · United States
- Susan Romie
- Melissa Lah
Women and Children HospitalRecruiting
North Adelaide, SA 5006 · Australia
- Drago Bratkovic
The Royal Children's HospitalRecruiting
Parkville, VIC 3052 · Australia
- Heidi Peters
Centre Hospitalier Universitaire (CHU) de Lille - Hôpital Jeanne de FlandreRecruiting
Lille, 59800 · France
- Karine Mention
Assistance Publique - Hôpitaux de Paris (AP-HP) - Hôpital Necker-Enfants MaladesRecruiting
Paris, 75015 · France
- Jean-Baptiste Arnoux
Centre Hospitalier Régional Universitaire (CHRU) de Tours - Hôpital ClochevilleRecruiting
Tours, 37044 · France
- François Labarthe, Dr.
Children's Health Ireland (CHI)Recruiting
Dublin, D01 YC67 · Ireland
- Joanne Hughes, Dr.
Pomorski Uniwersytet Medyczny w SzczecinieRecruiting
Szczecin, 70-204 · Poland
- Maria Gizewska
Instytut Matki i DzieckaRecruiting
Warsaw, 01-211 · Poland
- Joanna Taybert, Dr.
Birmingham Women's and Children's NHS Foundation TrustRecruiting
Birmingham, B4 6NH · United Kingdom
- Suresh Vijay

Terms used on this page · explanations by MedicalUpdates.ai

Women of childbearing potential: Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
at Screening: The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
study drug: A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
informed consent: The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
assent: A child's or dependent adult's agreement to take part, given alongside the formal consent of a parent or legal representative.
Baseline: Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them.
sponsor: The organisation or person that initiates the study and has authority over it. The sponsor may be a company, hospital, university, government agency or individual, and is not necessarily the organisation that funds the study.
glomerular filtration rate: A blood-test estimate of how well the kidneys are filtering. Lower numbers mean reduced kidney function; many studies set a minimum value.
exclusion criteria: The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
Key Inclusion Criteria: The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
open-label: No masking is used, so the assigned intervention is not deliberately hidden from participants or study staff.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

← Back to clinical trials