A Study of Sepiapterin in Participants With Phenylketonuria (PKU) (EPIPHENY)

August 26, 2026 updated by: PTC Therapeutics

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

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
56

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

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) <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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Sepiapterin
Participants will receive age- and weight-adjusted doses of sepiapterin orally once daily for up to 6 years.
Drug: Sepiapterin
Sepiapterin powder for oral use will be mixed in water or apple juice prior to administration.
Other Names:
  • PTC923
  • Sephience

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mean Change From Baseline in Full-scale Intelligence Quotient (FSIQ) Wechsler Preschool and Primary Scale of Intelligence - Fourth Edition (WPPSI-IV) Score
Time Frame: Baseline, Year 2
Analysis for participants ≥30 months to <6 years of age.
Baseline, Year 2
Mean Change From Baseline in FSIQ Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V) Score
Time Frame: Baseline, Year 2
Analysis for participants ≥6 years to 16 years of age.
Baseline, Year 2

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Phenylketonuria-Quality of Life (PKU-QOL) Questionnaire Score
Time Frame: Baseline up to 4 years
Baseline up to 4 years
Change From Baseline in the European Quality of Life - 5 Dimensions (EQ-5D) Score
Time Frame: Baseline up to 4 years
Baseline up to 4 years
Mean Change From Baseline in FSIQ (WPPSI-IV) Score
Time Frame: Baseline, Year 4
Analysis for participants aged ≥30 months to <6 years.
Baseline, Year 4
Mean Change From Baseline in FSIQ (WISC-V) Score
Time Frame: Baseline, Year 4
Analysis for participants aged ≥6 years to 16 years.
Baseline, Year 4
Change From Baseline in Mean Blood Phenylalanine (Phe) Levels
Time Frame: Baseline up to 6 years
Baseline up to 6 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
PTC Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 4, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 28, 2031

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 28, 2031

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 4, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 4, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 8, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 28, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 26, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PTC923-PKU-401
  • 2024-514435-20-00 (Other Identifier: EU CT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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