A Study of Sepiapterin in Participants With Phenylketonuria (PKU)

Official title

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

Overview

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.

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.

Interventions

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

Primary outcome measures

• 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]
• Mean Change From Baseline in FSIQ Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V) Score [Time frame: Baseline, Year 2]

Secondary outcome measures (5)

• Change From Baseline in Phenylketonuria-Quality of Life (PKU-QOL) Questionnaire Score [Time frame: 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]
• Mean Change From Baseline in FSIQ (WPPSI-IV) Score [Time frame: Baseline, Year 4]
• Mean Change From Baseline in FSIQ (WISC-V) Score [Time frame: Baseline, Year 4]
• Change From Baseline in Mean Blood Phenylalanine (Phe) Levels [Time frame: Baseline up to 6 years]

Eligibility criteria

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.

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

France · 3 centers

• Centre Hospitalier Universitaire (CHU) de Lille - Hôpital Jeanne de Flandre — Lille
• Assistance Publique - Hôpitaux de Paris (AP-HP) - Hôpital Necker-Enfants Malades — Paris
• Centre Hospitalier Régional Universitaire (CHRU) de Tours - Hôpital Clocheville — Tours

Australia · 2 centers

• Women and Children Hospital — North Adelaide
• The Royal Children's Hospital — Parkville

Poland · 2 centers

• Pomorski Uniwersytet Medyczny w Szczecinie — Szczecin
• Instytut Matki i Dziecka — Warsaw

United States · 1 center

• Indiana University School of Medicine — Indianapolis

Ireland · 1 center

• Children's Health Ireland (CHI) — Dublin

United Kingdom · 1 center

• Birmingham Women's and Children's NHS Foundation Trust — Birmingham

Identifiers

NCT: NCT06302348 · PTC923-PKU-401 · 2024-514435-20-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗