A Study of Sepiapterin in Participants With Phenylketonuria (PKU)
- Registration Number
- NCT06302348
- Lead Sponsor
- PTC Therapeutics
- 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.
- Detailed Description
The study includes 2 parts: Part 1 and 2. Part 1 is a sepiapterin-responsiveness test, and Part 2 is an open-label treatment period.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 56
Inclusion Criteria
- 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 up to 90 days after the last dose of the study drug.
- Established diagnosis of PKU with hyperphenylalaninemia (HPA) evidenced by at least 1 blood Phe measurement >600 μmol/L as documented in the medical history.
- For participants ≥1 month of age, a minimum of 1 documented blood Phe measurement <480 μmol/L within 1 month prior to Screening.
- For participants ≥1 month of age, 2 screening blood Phe concentration values must be in the range ≥120 to ≤480 μmol/L.
- Willing to continue prescribed diet during Screening and Part 1.
- For participants ≥30 months to <12 years of age, baseline FSIQ score ≥80.
Key
Exclusion Criteria
- History of allergies or adverse reactions to 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 dihydrochloride, 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 the prior 90 days of Screening.
Note: Other protocol-defined inclusion and exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Sepiapterin Sepiapterin Participants will receive age- and weight-adjusted doses of sepiapterin orally once daily for up to 6 years.
- Primary Outcome Measures
Name Time Method Mean Change From Baseline in Full-scale Intelligence Quotient (FSIQ) Wechsler Preschool and Primary Scale of Intelligence - Fourth Edition (WPPSI-IV) Score Baseline, Year 2 Analysis for participants ≥30 months to \<6 years of age.
Mean Change From Baseline in FSIQ Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V) Score Baseline, Year 2 Analysis for participants ≥6 years to 16 years of age.
- Secondary Outcome Measures
Name Time Method 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 Analysis for participants aged ≥30 months to \<6 years.
Mean Change From Baseline in FSIQ (WISC-V) Score Baseline, Year 4 Analysis for participants aged ≥6 years to 16 years.
Change From Baseline in Mean Blood Phenylalanine (Phe) Levels Baseline up to 6 years
Trial Locations
- Locations (1)
Indiana University
🇺🇸Indianapolis, Indiana, United States