A Long-Term Safety Study of PTC923 in Participants With Phenylketonuria

NCT05166161 | Active Not Recruiting Phase 3 FDA Drug

• 3 other identifiers: PTC923-MD-004-PKU2021-000497-282023-509229-31-00
• Study Type: interventional
• Target: 200
• Locations: 19 countries
• Sites: 46

Brief Summary

The main purpose of this study is to evaluate the long-term safety of PTC923 in participants with phenylketonuria, and to evaluate the changes from baseline in dietary phenylalanine (Phe)/protein consumption.

Conditions

Phenylketonuria

Outcome Measures

Primary Outcomes (2)

• Number of Treatment-Emergent Adverse Events (TEAEs)

  A TEAE is any unfavorable or unintended sign (including an abnormal laboratory finding), symptom or disease in a study participant who is administered study drug in this study

  Baseline up to end of study (up to 4 years)

• Change From Baseline in Dietary Phe/Protein Consumption at Week 26, Measured During Phe Tolerance Assessment Period

  Phe tolerance is defined as the total amount of dietary Phe (milligrams \[mg\]/kilogram \[kg\] per day) ingested while maintaining blood Phe levels within the range of 40 to 360 micromoles (μmol)/liter (L) (defined as ≥40 to \<360 μmol/L).

  Baseline, Week 26

Secondary Outcomes (7)

• Change From Baseline in Quality of Life (QOL) Using Phenylketonuria-Quality of Life (PKU-QOL) Questionnaire at Months 8, 14, 20, 26, 32, and 38

  Baseline, Months 8, 14, 20, 26, 32, and 38

• Change From Baseline in QOL Using the European Quality of Life - 5 Dimensions (EQ-5D) at Months 8, 14, 20, 26, 32, and 38

  Baseline, Months 8, 14, 20, 26, 32, and 38

• Palatability of PTC923

  Month 1 Day 1

• Acceptability/Ease of Administration of PTC923

  Month 1 Day 1

• Taste/Flavor Assessment Using a Facial Hedonic Scale

  Month 1 Day 1

Study Arms (1)

PTC923

EXPERIMENTAL

Participants will receive PTC923 7.5 mg/kg (participants 0 to \<6 months of age), 15 mg/kg (participants 6 to \<12 months of age), 30 mg/kg (participants 12 months to \<2 years of age), or 60 mg/kg (participants ≥2 years of age) orally once daily for a minimum of 12 months or until participant experiences lack of efficacy, adverse events (AEs) that lead to discontinuation, withdraws from treatment, or PTC923 is authorized and commercially available in the specific country.

Drug: PTC923

Interventions

PTC923 DRUG

PTC923 powder for oral use will be suspended in water or apple juice prior to administration.

Also known as: Sepiapterin, Sephience

PTC923

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of PKU with hyperphenylalaninemia (HPA) documented by past medical history of at least 2 blood Phe measurements ≥600 μmol/L.
• 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 up to 90 days after the last dose of the study drug.
• 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 up to 90 days after the last dose of study drug. Males must also refrain from sperm donations during this time period.
• Willing to continue current diet unchanged while participating in the study (unless specifically instructed to change diet during the study by the investigator).

You may not qualify if:

• Inability to tolerate oral medication.
• A female who is pregnant or breastfeeding, or considering pregnancy.
• Serious neuropsychiatric illness (for example, major depression) not currently under medical control, that in the opinion of the investigator or PTC, would interfere with the participant's ability to participate in the study or increase the risk of participation for that participant.
• Past medical history and/or evidence of renal impairment and/or condition including moderate/severe renal insufficiency (glomerular filtration rate \[GFR\] \<60 milliliters \[mL\]/minute \[min\] min as estimated most recently during qualifying participation in a feeder study) and/or under care of a nephrologist.
• Any other condition that in the opinion of the investigator or PTC, would interfere with the participant's ability to participate in the study or increase the risk of participation for that participant.
• Requirement for concomitant treatment with any drug known to inhibit folate synthesis (for example, methotrexate).
• Concomitant treatment with tetrahydrobiopterin (BH4) supplementation (for example, sapropterin dihydrochloride, KUVAN) or pegvaliase-pqpz (PALYNZIQ).
• Additional criteria for non-feeder participants who did not participate in a feeder study:
• 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.
• History of gastric surgery, including Roux-en-Y gastric bypass surgery or an antrectomy with vagotomy, or gastrectomy.
• History of allergies or adverse reactions to synthetic BH4 or sepiapterin.
• Any clinically significant laboratory abnormality as determined by the investigator.
• Any abnormal physical examination and/or laboratory findings indicative of signs or symptoms of renal disease, including calculated GFR \<60 milliliters (mL)/minute/1.73 square meter (m\^2).
• 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.

Sponsors & Collaborators

• PTC Therapeutics: lead

Study Sites (46)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

UF College of Medicine, Department of Pediatrics Division of Genetics and Metabolism

Gainesville, Florida, 32610, United States

Location

Indiana University School of Medicine Department of Medical and Molecular Genetics

Indianapolis, Indiana, 46202, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Icahn School of Medicine at Mount Sinai (ISMMS)

New York, New York, 10009, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

University of Utah

Salt Lake City, Utah, 84108, United States

Location

The Queensland Children's Hospital

South Brisbane, Brisbane, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

PARC Clinical Research

Adelaide, South Australia, SA 5000, Australia

Location

Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

Hospital de clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo

Ribeirão Preto, São Paulo, 14051-140, Brazil

Location

Metabolics and Genetics in Calgary (MAGIC) Clinic, Ltd.

Calgary, Alberta, T2E 7Z4, Canada

Location

McMaster Children's Hospital Hamilton Health Sciences

Hamilton, Ontario, L8N 3Z5, Canada

Location

The Hospital for Sick Children University of Toronto Adult Clinic: The Fred A Litwin Family Centre in Genetic Medicine University Health Network & Mt. Sinai Hospital

Toronto, Ontario, M5G 1X8, Canada

Location

Fakultní nemocnice Královské Vinohrady Klinika dětí a dorostu Ambulance pro léčbu PKU a HPA

Prague, 100 34, Czechia

Location

Copenhagen University Hospital, Rigshospitalet

Copenhagen, DK-2100, Denmark

Location

Hôpital Necker-Enfants Malades - Centre de Référence des Maladies Héréditaires du Métabolisme

Paris, 75015, France

Location

Medical Genetics and Laboratory Diagnostics Center

Tbilisi, 0159, Georgia

Location

University Children's Hospital Hamburg Eppendorf (Kinder-UKE) Klinik für Kinder- und Jugendmedizin (Kinder-UKE)

Hamburg, 20246, Germany

Location

Universitätsklinikum Heidelberg / Zentrum für Kinder- und Jugendmedizin / Sektion für Neuropädiatrie & Stoffwechselmedizin

Heidelberg, 69120, Germany

Location

Universitätsklinikum Münster

Münster, 48149, Germany

Location

Azienda Ospedaliera-Universita Padova

Padua, Veneto, 35129, Italy

Location

Department of Human Neuroscience, Child and Adolescent Neuropsychiatry, Policlinico Umberto I

Rome, 00185, Italy

Location

PTC Clinical Site 1

Multiple Locations, Japan

Location

PTC Clinical Site 2

Multiple Locations, Japan

Location

PTC Clinical Site 3

Multiple Locations, Japan

Location

PanAmerican Clinical Research

Guadalajara, Jalisco, 44670, Mexico

Location

UMCG Beatrix Children's Hospital

Groningen, 9713 GZ, Netherlands

Location

Pomorski Uniwersytet Medyczny w Szczecinie Centrum Wsparcia Badań Klinicznych

Szczecin, 71-252, Poland

Location

CENTRO HOSPITALAR UNIVERSITÁRIO LISBOA NORTE Hospital de Santa Maria,

Lisbon, Estremadura, 1649-035, Portugal

Location

CENTRO HOSPITALAR UNIVERSITÁRIO LISBOA NORTE Hospital de Santa Maria

Lisbon, Estremadura, 1649-035, Portugal

Location

Centro Hospitalar Universitário Do Porto, Epe

Porto, 4099-001, Portugal

Location

Univerzitetni klinicni center Ljubljana

Ljubljana, 1000, Slovenia

Location

Hospital Sant Joan de Déu

Barcelona, Esplugues de Llobregat, 08950, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hacettepe University Medical Faculty

Altındağ, Ankara, 06230, Turkey (Türkiye)

Location

Gazi Üniversitesi Tıp Fakültesi

Yenimahalle, Ankara, 06500, Turkey (Türkiye)

Location

İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi

Fatih, Istanbul, 34098, Turkey (Türkiye)

Location

Ege University Faculty of Medicine Children Hospital

Bornova, İzmir, 35100, Turkey (Türkiye)

Location

Çukurova Üniversitesi Tıp Fakültesi Balcalı Hastanesi

Adana, 01330, Turkey (Türkiye)

Location

Birmingham Children's Hospital NHS Foundation Trust

Birmingham, B4 6NH, United Kingdom

Location

UNIVERSITY HOSPITALS BIRMINGHAM NHS Foundation Trust

Birmingham, United Kingdom

Location

Great Ormond Street Hospital

London, WC1N 3JH, United Kingdom

Location

Related Publications (1)

• van Spronsen F, Peters H, Margvelashvili L, Agladze D, Schwartz IVD, Gizewska M, Hamazaki T, Guilder L, MacDonald A, Vijay S, Inwood A, Minami M, Fjellbirkeland O, Lund A, Lah M, Thomas JA, Longo N, Kiykim E, Ishige M, Burlina A, Belanger-Quintana A, Rutsch F, Opladen T, Mungan H, Ezgu F, Bratkovic D, Chakrapani A, Ito T, Guimas A, Zori R, Tchan M, Sacharow S, Oliveira A, Janeiro P, Guerra IC, Plana JC, Yildiz Y, Canda E, Khan A, Vockley J, Breilyn MS, Manti F, Larkin A, Hughes C, Liu E, Gao L, Ingalls K, Smith N, Muntau AC. Effect of long-term sepiapterin treatment on dietary phenylalanine tolerance in patients with phenylketonuria: Interim results from the phase 3 APHENITY Extension Study. Genet Med. 2026 Apr;28(4):101683. doi: 10.1016/j.gim.2026.101683. Epub 2026 Jan 12.

  PMID: 41537382 DERIVED

MeSH Terms

Conditions

Phenylketonurias

Interventions

sepiapterin

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2021
• First Posted: December 21, 2021
• Study Start: February 14, 2022
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

NL (1); FR (1); JP (3); GB (3); DE (3); US (7); CA (3); TU (5); AU (4); SL (1); CZ (1); ES (3); GE (1); PL (1); IT (2); DK (1); PT (3); BR (2); ME (1)