A study of sepiapterin in participants with phenylketonuria (PKU) (EPIPHENY)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

PTC Therapeutics Inc.

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Phenomena and Processes [G] - Metabolism [G03]

Trial duration

23 Dec 2025 → ongoing

Decision date (initial)

2025-07-18

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

PTC Therapeutics Inc.

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy

To evaluate the long-term efficacy of sepiapterin on preserving neurocognitive functioning in children with phenylketonuria (PKU) when treatment is initiated in early childhood

Secondary objectives 1

1. To evaluate the effect of sepiapterin on quality of life (QOL)

Conditions and MedDRA coding

Phenylketonuria

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

EMA paediatric investigation plan (PIP)

EMEA-003027-PIP02-23

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 01. Informed consent, and if necessary, assent (with parent/legally designated representative consent).
2. 02. Male or female outpatients <10 years of age at the time of informed consent/assent form signature.
3. 03. Parent(s) or legally designated representative(s) willing and able to comply with all study procedures.
4. 04. Women of childbearing potential, as defined in CTCG 2024: see protocol for more details; must have a negative pregnancy test at Screening and agree to abstinence or the use of at least 1 highly effective form of contraception (with a failure rate of <1% per year when used consistently and correctly); Highly effective contraception or abstinence must be continued for the duration of the study and for at least 90 days after the last dose of the study drug.
5. 05. Males who are sexually active with women of childbearing potential who have not had a vasectomy must agree to use a barrier method of birth control during the study and for at least 90 days after the last dose of study drug. Males must also refrain from sperm donations during this time period. Males who are abstinent will not be required to use a contraceptive method unless they become sexually active. Males who have undergone a vasectomy are not required to use a contraceptive method if at least 16 weeks post procedure.
6. 06. Willing to maintain prescribed daily protein/Phe during Screening and Part 1.
7. 07. For participants ≥1 month of age at Screening: Established diagnosis of PKU with hyperphenylalaninemia evidenced by at least 2 blood Phe measurement ≥600 μmol/L as documented in the medical history.
8. 08. For participants ≥1 month of age at Screening: A minimum of 1 documented blood Phe measurement <480 μmol/L within 1 month prior to Screening.
9. 09. For participants ≥1 month of age at Screening: Two screening blood Phe concentration values must be in the range ≥120 to ≤480 μmol/L.
10. 10. For participants <1 month of age at the time of informed consent/assent only: Blood Phe at newborn screening ≥600 μmol/L.
11. 11. For participants ≥30 months to <10 years of age: Baseline FSIQ score ≥80.

Exclusion criteria 15

1. 01. The individual and/or parent(s)/legally designated representative(s), in the opinion of the investigator, is/are unwilling or unable to adhere to the requirements of the study.
2. 10. Gastrointestinal disease (such as irritable bowel syndrome, inflammatory bowel disease, chronic gastritis, and peptic ulcer disease, etc) that could affect the absorption of study drug.
3. 11. History of gastric surgery, including Roux-en-Y gastric bypass surgery or an antrectomy with vagotomy, or gastrectomy.
4. 12. Any clinically significant laboratory abnormality as determined by the investigator. In general, each laboratory value from screening and baseline chemistry and hematology panels should fall within the limits of the normal laboratory reference range, unless deemed not clinically significant by the investigator.
5. 13. 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 <60 mL/min/1.73 m2.
6. 14. Major surgery within 90 days prior to Screening visit.
7. 02. History of allergies or adverse reactions to any of the ingredients or excipients of synthetic tetrahydrobiopterin (BH4) or sepiapterin.
8. 03. Inability to tolerate oral medication.
9. 04. A female who is pregnant or breastfeeding or considering pregnancy.
10. 05. Current use of methotrexate, pemetrexed, trimetrexate, or other dihydrofolate reductase inhibitors.
11. 06. Serious neuropsychiatric illness (eg, 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.
12. 07. Treatment with BH4 supplementation (sapropterin, KUVAN) within 3 months prior to Screening.
13. 08. Current participation in another investigational drug study or use of any investigational agent within 30 days prior to Screening.
14. 09. Confirmed diagnosis of a primary BH4 deficiency as evidenced by biallelic pathogenic mutations in 6-pyruvoyltetrahydropterin synthase, recessive GTP cyclohydrolase I, sepiapterin reductase, quinoid dihydropteridine reductase, or pterin 4-alphacarbinolamine dehydratase genes.
15. 15. Previous treatment for >6 weeks with sepiapterin (ie, SEPHIENCE™)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Mean change in full-scale intelligence quotient (FSIQ) (WPPSI-IV or WISC-V) over a 2-year period: WPPSI-IV (Wechsler Preschool and Primary Scale of Intelligence - Fourth Edition): for participants ≥30 months to <6 years of age, WISC-V (Wechsler Intelligence Scale for Children - Fifth Edition): for participants ≥6 years to 16 years of age

Secondary endpoints 4

1. 01. Change from baseline in phenylketonuriaquality of life (PKU-QOL) questionnaire score over time
2. 02. Change from baseline in European Quality of Life - 5 Dimensions (EQ-5D) score over time
3. 03. Mean change in FSIQ (WPPSI-IV or WISC-V) over a 4-year period
4. 04. Change of phenylalanine (Phe) levels over time

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

PTC Therapeutics Inc.

Sponsor organisation

PTC Therapeutics Inc.

Address

500 Warren Corporate Center Drive

City

Warren

Postcode

07059

Country

United States

Scientific contact point

Organisation

PTC Therapeutics Inc.

Contact name

Kim Ingalls

Public contact point

Organisation

PTC Therapeutics Inc.

Contact name

Kim Ingalls

Third parties 8

Locations

4 EU/EEA countries · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 35 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

3 submissions — initial application plus substantial / non-substantial modifications