A Study of Sepiapterin in Participants With Phenylketonuria (PKU)

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified February 2026 by PTC Therapeutics
Sponsor
PTC Therapeutics
Information Provided by (Responsible Party)
PTC Therapeutics
Clinicaltrials.gov Identifier
NCT06302348
Other Study ID Numbers:
PTC923-PKU-401
First Submitted
March 3, 2024
First Posted
March 7, 2024
Last Update Posted
March 26, 2026
Last Verified
February 2026

ClinicalTrials.gov processed this data on March 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study 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.

Condition or DiseaseIntervention/Treatment
Phenylketonuria
Drug: Sepiapterin

Study Design

Study TypeInterventional
Actual Enrollment56 participants
Design AllocationN/A
Interventional ModelSingle Group Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleA Phase 3b Open-Label Study of Long-Term Neurocognitive Outcomes in Children With Phenylketonuria Treated With Sepiapterin
Study Start DateMarch 3, 2024
Actual Primary Completion Date4yrs 10mos from now
Actual Study Completion Date4yrs 10mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
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.

Outcome Measures

Primary Outcome Measures
  1. 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.
  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.
Secondary Outcome Measures
  1. Change From Baseline in Phenylketonuria-Quality of Life (PKU-QOL) Questionnaire Score
  2. Change From Baseline in the European Quality of Life - 5 Dimensions (EQ-5D) Score
  3. Mean Change From Baseline in FSIQ (WPPSI-IV) Score
    Analysis for participants aged ≥30 months to \<6 years.
  4. Mean Change From Baseline in FSIQ (WISC-V) Score
    Analysis for participants aged ≥6 years to 16 years.
  5. Change From Baseline in Mean Blood Phenylalanine (Phe) Levels

Eligibility Criteria

Ages Eligible for Study(Child)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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.

Contacts and Locations

Sponsors and CollaboratorsPTC Therapeutics
Locations
Indiana University School of Medicine | Indianapolis Indiana, United States, 46202Women and Children Hospital | North Adelaide , Australia, SA 5006The Royal Children's Hospital | Parkville , Australia, VIC 3052Pomorski Uniwersytet Medyczny w Szczecinie | Szczecin , Poland, 70-204Birmingham Women's and Children's NHS Foundation Trust | Birmingham , United Kingdom, B4 6NH