A Study of Sepiapterin in Participants With Phenylketonuria (PKU)

NCT06302348 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: PTC923-PKU-4012024-514435-20-00
• Study Type: interventional
• Target: 56
• Locations: 6 countries
• Sites: 8

Brief Summary

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.

Conditions

Phenylketonuria

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• 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

  Baseline, Year 4

• Mean Change From Baseline in FSIQ (WISC-V) Score

  Baseline, Year 4

• Change From Baseline in Mean Blood Phenylalanine (Phe) Levels

  Baseline up to 6 years

Study Arms (1)

Sepiapterin

EXPERIMENTAL

Participants will receive age- and weight-adjusted doses of sepiapterin orally once daily for up to 6 years.

Drug: Sepiapterin

Interventions

Sepiapterin DRUG

Sepiapterin powder for oral use will be mixed in water or apple juice prior to administration.

Also known as: PTC923, Sephience

Sepiapterin

Eligibility Criteria

• Age: Up to 9 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• PTC Therapeutics: lead

Study Sites (8)

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

RECRUITING

Women and Children Hospital

North Adelaide, SA 5006, Australia

RECRUITING

The Royal Children's Hospital

Parkville, VIC 3052, Australia

RECRUITING

Centre Hospitalier Régional Universitaire (CHRU) de Tours - Hôpital Clocheville

Tours, 37044, France

RECRUITING

Children's Health Ireland (CHI)

Dublin, D01 YC67, Ireland

RECRUITING

Pomorski Uniwersytet Medyczny w Szczecinie

Szczecin, 70-204, Poland

RECRUITING

Instytut Matki i Dziecka

Warsaw, 01-211, Poland

RECRUITING

Birmingham Women's and Children's NHS Foundation Trust

Birmingham, B4 6NH, United Kingdom

RECRUITING

MeSH Terms

Conditions

Phenylketonurias

Interventions

sepiapterin

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Patient Advocacy

CONTACT

1-866-562-4620; medinfo@ptcbio.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2024
• First Posted: March 8, 2024
• Study Start: March 4, 2024
• Primary Completion (Estimated): February 28, 2031
• Study Completion (Estimated): February 28, 2031
• Last Updated: May 6, 2026

Record last verified: 2026-04

Locations

PL (2); GB (1); AU (2); US (1); FR (1); IE (1)