Sepiapterin: Sepiapterin powder for oral use will be mixed in water or apple juice prior to administration.
Study 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.
Eligibility
Sex
ALL
Min age
—
Max age
9 Years
Healthy volunteers
No
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.
Primary outcome measure(s)
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.
Trial sites (10)
Facility
City
Region
Status
Indiana University School of Medicine
Indianapolis
Indiana
Recruiting
Women and Children Hospital
North Adelaide
Australia
Recruiting
The Royal Children's Hospital
Parkville
Australia
Recruiting
Centre Hospitalier Universitaire (CHU) de Lille - Hôpital Jeanne de Flandre
Lille
France
Recruiting
Assistance Publique - Hôpitaux de Paris (AP-HP) - Hôpital Necker-Enfants Malades
Paris
France
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
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time on our Cookie Policy page. See also our Privacy Policy.