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

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: Recruiting
• Conditions: Phenylketonuria
• Intervention / Treatment: Drug: Sepiapterin

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: Interventional
• Enrollment (Estimated): 56
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Patient Advocacy; Phone Number: 1-866-562-4620; Email: medinfo@ptcbio.com

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
  • 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

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

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	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	Analysis for participants ≥6 years to 16 years of age.	Baseline, Year 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Phenylketonuria-Quality of Life (PKU-QOL) Questionnaire Score		Baseline up to 4 years
Change From Baseline in the European Quality of Life - 5 Dimensions (EQ-5D) Score		Baseline up to 4 years
Mean Change From Baseline in FSIQ (WPPSI-IV) Score	Analysis for participants aged ≥30 months to <6 years.	Baseline, Year 4
Mean Change From Baseline in FSIQ (WISC-V) Score	Analysis for participants aged ≥6 years to 16 years.	Baseline, Year 4
Change From Baseline in Mean Blood Phenylalanine (Phe) Levels		Baseline up to 6 years

Collaborators and Investigators

• Sponsor: PTC Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): March 4, 2024
• Primary Completion (Estimated): February 28, 2031
• Study Completion (Estimated): February 28, 2031

Study Registration Dates

• First Submitted: March 4, 2024
• First Submitted That Met QC Criteria: March 4, 2024
• First Posted (Actual): March 8, 2024

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Amino Acid Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Phenylketonurias; sepiapterin
• Other Study ID 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