Sepiapterin for Phenylketonuria (PKU)

Inclusion criteria

• {"criterion_text":"- 01. Informed consent, and if necessary, assent (with parent/legally designated representative consent).\n- 10. For participants <1 month of age at the time of informed consent/assent only: Blood Phe at newborn screening ≥600 μmol/L.\n- 11. For participants ≥30 months to <10 years of age: Baseline FSIQ score ≥80.\n- 02. Male or female outpatients <10 years of age at the time of informed consent/assent form signature.\n- 03. Parent(s) or legally designated representative(s) willing and able to comply with all study procedures.\n- 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.\n- 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.\n- 06. Willing to maintain prescribed daily protein/Phe during Screening and Part 1.\n- 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.\n- 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.\n- 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."}

Exclusion criteria

• {"criterion_text":"- 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.\n- 05. Current use of methotrexate, pemetrexed, trimetrexate, or other dihydrofolate reductase inhibitors.\n- 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.\n- 07. Treatment with BH4 supplementation (sapropterin, KUVAN) within 3 months prior to Screening.\n- 08. Current participation in another investigational drug study or use of any investigational agent within 30 days prior to Screening.\n- 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.\n- 15. Previous treatment for >6 weeks with sepiapterin (ie, SEPHIENCE™)\n- 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.\n- 11. History of gastric surgery, including Roux-en-Y gastric bypass surgery or an antrectomy with vagotomy, or gastrectomy.\n- 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.\n- 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.\n- 14. Major surgery within 90 days prior to Screening visit.\n- 02. History of allergies or adverse reactions to any of the ingredients or excipients of synthetic tetrahydrobiopterin (BH4) or sepiapterin.\n- 03. Inability to tolerate oral medication.\n- 04. A female who is pregnant or breastfeeding or considering pregnancy."}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"FSIQ measured using WPPSI-IV for participants ≥30 months to <6 years and WISC-V for participants ≥6 years to 16 years; outcome is mean change in FSIQ over a 2-year period."}

Secondary endpoints

• {"endpoint_text":"- 01. Change from baseline in phenylketonuriaquality of life (PKU-QOL) questionnaire score over time","definition_or_measurement_approach":"Measured as change from baseline in PKU-QOL questionnaire score over time (questionnaire-based patient/parent-reported outcome)."}
• {"endpoint_text":"- 02. Change from baseline in European Quality of Life - 5 Dimensions (EQ-5D) score over time","definition_or_measurement_approach":"Measured as change from baseline in EQ-5D score over time (standardized health-related quality of life instrument)."}
• {"endpoint_text":"- 03. Mean change in FSIQ (WPPSI-IV or WISC-V) over a 4-year period","definition_or_measurement_approach":"FSIQ measured using WPPSI-IV (for younger children) or WISC-V (for older children); outcome is mean change over 4 years."}
• {"endpoint_text":"- 04. Change of phenylalanine (Phe) levels over time","definition_or_measurement_approach":"Measured as change in blood phenylalanine (Phe) concentrations over time (laboratory measurements)."}

Ireland

Earliest CTIS Part Ii Submission Date

19-06-2025

Latest Decision Or Authorization Date

14-07-2025

Processing Time Days

25

Number Of Sites

1

Number Of Participants

15

Poland

Earliest CTIS Part Ii Submission Date

26-06-2025

Latest Decision Or Authorization Date

18-07-2025

Processing Time Days

22

Number Of Sites

2

Number Of Participants

15

Sweden

Earliest CTIS Part Ii Submission Date

06-06-2025

Latest Decision Or Authorization Date

16-07-2025

Processing Time Days

40

Number Of Sites

1

Number Of Participants

15

France

Earliest CTIS Part Ii Submission Date

24-06-2025

Latest Decision Or Authorization Date

18-07-2025

Processing Time Days

24

Number Of Sites

3

Number Of Participants

15

Primary sponsor

Full Name

PTC Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Iqvia Rds Inc.

Responsibilities

sponsorDuties codes: [8]; pharmacovigilance contact

Name

CTI Clinical Trial and Consulting Services Europe GmbH

Responsibilities

regulatory and trial management duties (sponsorDuties codes: [1,12,2,5])

Name

PPD Development LP

Responsibilities

DSMB and related functions (sponsorDuties: [15])

Name

Everest Clinical Research Corporation

Responsibilities

site-related functions (sponsorDuties: [6])

Third parties

• {"country":"United States","full_name":"Iqvia Rds Inc.","duties_or_roles":"sponsorDuties codes: [8]; contact email: pharmacovigilance@ptcbio.com","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"CTI Clinical Trial and Consulting Services Europe GmbH","duties_or_roles":"sponsorDuties codes: [1,12,2,5]; contact email: regulatoryeurope@ctifacts.com","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Mde Healthcare Services Limited","duties_or_roles":"sponsorDuties: [15] (Travel Managament); contact email: info@mdgroup.com","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties: [15 (Site Payments), 7]; contact email: info@medidata.com","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"sponsorDuties: [15] (DSMB); contact email: EUCTRInquiry.sm@ppd.com","organisation_type":"Pharmaceutical company"}
• {"country":"Canada","full_name":"Everest Clinical Research Corporation","duties_or_roles":"sponsorDuties: [6]; contact email: corporate.communication@ecrscorp.com","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"MEDPACE LABORATORIES","duties_or_roles":"sponsorDuties: [4]; contact email: MRL-BE-PM@medpace.com","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"sponsorDuties: [3]; contact email: support@suvoda.com","organisation_type":"Non-Pharmaceutical company"}