Phenylketonuria
Conditions
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 an open-label sepiapterin-responsiveness test and Part 2 is an open-label treatment period.
Interventions
DRUGSepiapterin
Sepiapterin powder for oral use will be mixed in water or apple juice prior to administration.
Sponsors
PTC Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 9 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Countries
Australia, France, Ireland, Poland, United Kingdom, United States
Contacts
CONTACTPatient Advocacy
Outcome results
None listed