Evaluating sepiapterin for children with phenylketonuria

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

This study is testing if sepiapterin can help children with phenylketonuria keep their brain function and development healthy over time.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 56 (estimated)
• Ages: N/A to 9 Years
• Sex: All
• Sponsor: PTC Therapeutics (Industry-sponsored)
• Locations: 8 sites (Indianapolis, Indiana and 7 other locations)
• Trial ID: NCT06302348 on ClinicalTrials.gov

What this trial studies

This trial aims to assess the long-term effectiveness of sepiapterin in preserving neurocognitive function in children diagnosed with phenylketonuria (PKU). The study is divided into two parts: the first part involves an open-label test to determine responsiveness to sepiapterin, while the second part consists of an open-label treatment phase. Participants will be monitored for their blood phenylalanine levels and overall cognitive development throughout the study.

Who should consider this trial

Good fit: Ideal candidates include children diagnosed with PKU who are at least one month old and have specific blood phenylalanine levels.

Not a fit: Patients who do not have a confirmed diagnosis of PKU or whose blood phenylalanine levels do not meet the study criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve cognitive outcomes for children with PKU.

How similar studies have performed: Other studies have explored treatments for PKU, but the specific use of sepiapterin in this context is relatively novel.

Eligibility criteria

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.

Where this trial is running

Indianapolis, Indiana and 7 other locations

• Indiana University School of Medicine — Indianapolis, Indiana, United States (Recruiting)
• Women and Children Hospital — North Adelaide, Australia (Recruiting)
• The Royal Children's Hospital — Parkville, Australia (Recruiting)
• Centre Hospitalier Régional Universitaire (CHRU) de Tours - Hôpital Clocheville — Tours, France (Recruiting)
• Children's Health Ireland (CHI) — Dublin, Ireland (Recruiting)
• Pomorski Uniwersytet Medyczny w Szczecinie — Szczecin, Poland (Recruiting)
• Instytut Matki i Dziecka — Warsaw, Poland (Recruiting)
• Birmingham Women's and Children's NHS Foundation Trust — Birmingham, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Patient Advocacy

Conditions Phenylketonuria