PhenylketonuriaPhase 3EPIPHENYNCT06302348
A Study of Sepiapterin in Participants With Phenylketonuria (PKU)
A Phase 3 study testing Sepiapterin in people with Phenylketonuria, run by PTC Therapeutics at 14 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 9 years
- Conditions the study is for
- Phenylketonuria
- What is being tested?
- Sepiapterin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 14 sitesin 7 countries
- Study dates
- 4 Mar 2024to 28 Feb 2031
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 9 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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.
Show all 11Show fewer
- 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.
Who cannot join
- 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.
Show all 10Show fewer
- 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.
Trial locations and contacts
14 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
14 sites in 7 countries
Australia4 sites, 4 recruiting
- Recruiting
Perth Children's Hospital
Nedlands, WA 6009
Maina Kava
- Recruiting
Women and Children Hospital
North Adelaide, SA 5006
Drago Bratkovic
- Recruiting
The Royal Children's Hospital
Parkville, VIC 3052
Heidi Peters
- Recruiting
Children's Health Queensland -Queenslan Children Hospital
South Brisbane, QLD 4101
Anita Inwood
France3 sites, 3 recruiting
- Recruiting
Centre Hospitalier Universitaire (CHU) de Lille - Hôpital Jeanne de Flandre
Lille, 59800
Karine Mention
- Recruiting
Assistance Publique - Hôpitaux de Paris (AP-HP) - Hôpital Necker-Enfants Malades
Paris, 75015
Jean-Baptiste Arnoux
- Recruiting
Centre Hospitalier Régional Universitaire (CHRU) de Tours - Hôpital Clocheville
Tours, 37000
François Labarthe, Dr.
Poland2 sites, 2 recruiting
- Recruiting
Pomorski Uniwersytet Medyczny w Szczecinie
Szczecin, 70-204
Maria Gizewska
- Recruiting
Instytut Matki i Dziecka
Warsaw, 01-211
Joanna Taybert, Dr.
United Kingdom2 sites, 2 recruiting
- Recruiting
Birmingham Women's and Children's NHS Foundation Trust
Birmingham, B4 6NH
Suresh Vijay
- Recruiting
Great Ormond Street Hospital
London, WC1N 3JH
Anupam Chakrapani
United States1 site, 1 recruiting
- Recruiting
Indiana University School of Medicine
Indianapolis, Indiana, 46202
Susan Romie
Melissa Lah
Ireland1 site, 1 recruiting
- Recruiting
Children's Health Ireland (CHI)
Dublin, D01 YC67
Joanne Hughes, Dr.
Sweden1 site, 1 recruiting
- Recruiting
Karolinska Universitetssjukhuset - Astrid Lindgrens Barnsjukhus
Stockholm, 171 76
Svetlana Lajic
About this study
Official title: A Phase 3b Open-Label Study of Long-Term Neurocognitive Outcomes in Children With Phenylketonuria Treated With Sepiapterin
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.
Read the 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.
- Conditions
- Phenylketonuria
- Being tested
- Sepiapterin
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SepiapterinDrug
Also called PTC923, Sephience
Sepiapterin powder for oral use will be mixed in water or apple juice prior to administration.
| Study group | Role | What they receive |
|---|---|---|
| Sepiapterin | Experimental | Participants will receive age- and weight-adjusted doses of sepiapterin orally once daily for up to 6 years. Receives: Drug: Sepiapterin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change From Baseline in Full-scale Intelligence Quotient (FSIQ) Wechsler Preschool and Primary Scale of Intelligence - Fourth Edition (WPPSI-IV) Score
Analysis for participants ≥30 months to <6 years of age.
Measured: Baseline, Year 2
Mean Change From Baseline in FSIQ Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V) Score
Analysis for participants ≥6 years to 16 years of age.
Measured: Baseline, Year 2
Secondary outcomes (5)
Change From Baseline in Phenylketonuria-Quality of Life (PKU-QOL) Questionnaire Score
Measured: Baseline up to 4 years
Change From Baseline in the European Quality of Life - 5 Dimensions (EQ-5D) Score
Measured: Baseline up to 4 years
Mean Change From Baseline in FSIQ (WPPSI-IV) Score
Analysis for participants aged ≥30 months to <6 years.
Measured: Baseline, Year 4
Mean Change From Baseline in FSIQ (WISC-V) Score
Analysis for participants aged ≥6 years to 16 years.
Measured: Baseline, Year 4
Change From Baseline in Mean Blood Phenylalanine (Phe) Levels
Measured: Baseline up to 6 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2024
- Study start4 Mar 2024
- Primary completion28 Feb 2031 (estimated)
- Study completion28 Feb 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PhenylketonuriaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- PTC Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06302348
- Sponsor's protocol ID
- PTC923-PKU-401
- Other IDs
- 2024-514435-20-00
- Acronym
- EPIPHENY
- Status last verified
- Oct 2026
- First submitted
- 4 Mar 2024
- Last updated
- 23 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No