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

Recruitment Status
ACTIVE, NOT RECRUITING
(See Contacts and Locations)Verified February 2026 by PTC Therapeutics
Sponsor
PTC Therapeutics
Information Provided by (Responsible Party)
PTC Therapeutics
Clinicaltrials.gov Identifier
NCT05166161
Other Study ID Numbers:
PTC923-MD-004-PKU
First Submitted
December 7, 2021
First Posted
December 20, 2021
Last Update Posted
March 22, 2026
Last Verified
February 2026

ClinicalTrials.gov processed this data on March 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Eligible participants are:

Feeder participants: those who have completed a Phase 3 PTC Therapeutics (PTC) sponsored feeder study.

Non-feeder controlled participants: those who have not completed a feeder study and have blood Phe levels \<360 μmol/L at study entry.

Non-feeder uncontrolled participants: those who have not completed a feeder study and have blood Phe levels ≥360 μmol/L at study entry.

Condition or DiseaseIntervention/Treatment
Phenylketonuria
Drug: PTC923

Study Design

Study TypeInterventional
Actual Enrollment200 participants
Design AllocationN/A
Interventional ModelSingle Group Assignment
MaskingNone (Open Label)
Primary PurposeTreatment
Official TitleA Phase 3 Open-Label Study of PTC923 (Sepiapterin) in Phenylketonuria
Study Start DateFebruary 13, 2022
Actual Primary Completion Date2mos 1w from now
Actual Study Completion Date2mos 1w from now

Groups and Cohorts

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

Outcome Measures

Primary Outcome Measures
  1. 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
  2. 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 (&mu;mol)/liter (L) (defined as &ge;40 to \&lt;360 &mu;mol/L).
Secondary Outcome Measures
  1. 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
    QOL using PKU-QOL questionnaire will be assessed in the subset of participants who are able to complete the PKU-QOL (that is, participants whose primary language is English \[British or American\], Turkish, Dutch, German, Spanish, Italian, Portuguese, or French) (ages 6 to 8 years Parent PKU-QOL; ages 9 to 11 years Child PKU-QOL; ages 12 to 17 years Adolescent PKU-QOL; ages &ge;18 years Adult PKU-QOL).
  2. Change From Baseline in QOL Using the European Quality of Life - 5 Dimensions (EQ-5D) at Months 8, 14, 20, 26, 32, and 38
    QOL will be assessed using the EQ-5D (EQ-5D-Y Proxy Version 1 \[3 to 7 years\]; EQ-5D-Y \[8 to 15 years\]; EQ-5D-5L (\[&ge;16 years\]).
  3. Palatability of PTC923
    For participants \&lt;5 years of age, palatability will be indirectly assessed by the parent(s)/caregiver(s) of participants using the following: On the basis of the reaction/facial expression of your child, do you think that the medication is (pleasant, not sure, unpleasant)?
  4. Acceptability/Ease of Administration of PTC923
    For all participants \&lt;12 years of age, parent(s)/caregiver(s) will rate the acceptability/ease of administration, with the following question: Do you sometimes have problems in giving the medication to your child because he/she refuses to take it or throws it up? (Yes/No).
  5. Taste/Flavor Assessment Using a Facial Hedonic Scale
    For participants &ge;5 to \&lt;18 years of age who are able to comply with the instructions, the participant will rate the taste/flavor using a facial hedonic scale (5=really good; 4=good; 3=not sure; 2=bad; 1=really bad).
  6. Plasma Sepiapterin Concentration
  7. Plasma BH4 Concentration

Eligibility Criteria

Ages Eligible for Study(Child, Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
Inclusion Criteria
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).
Exclusion Criteria
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.

Contacts and Locations

Sponsors and CollaboratorsPTC Therapeutics
Locations
Children's Hospital Colorado | Aurora Colorado, United States, 80045UF College of Medicine, Department of Pediatrics Division of Genetics and Metabolism | Gainesville Florida, United States, 32610Indiana University School of Medicine Department of Medical and Molecular Genetics | Indianapolis Indiana, United States, 46202Boston Children's Hospital | Boston Massachusetts, United States, 02115Icahn School of Medicine at Mount Sinai (ISMMS) | New York New York, United States, 10009UPMC Children's Hospital of Pittsburgh | Pittsburgh Pennsylvania, United States, 15224University of Utah | Salt Lake City Utah, United States, 84108Westmead Hospital | Westmead New South Wales, Australia, 2145PARC Clinical Research | Adelaide South Australia, Australia, SA 5000Royal Children's Hospital | Parkville Victoria, Australia, 3052Hospital de clinicas de Porto Alegre | Porto Alegre Rio Grande do Sul, Brazil, 90035-903Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo | Ribeirão Preto São Paulo, Brazil, 14051-140Metabolics and Genetics in Calgary (MAGIC) Clinic, Ltd. | Calgary Alberta, Canada, T2E 7Z4McMaster Children's Hospital Hamilton Health Sciences | Hamilton Ontario, Canada, L8N 3Z5The 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, Canada, M5G 1X8Fakultní nemocnice Královské Vinohrady Klinika dětí a dorostu Ambulance pro léčbu PKU a HPA | Prague , Czechia, 100 34Copenhagen University Hospital, Rigshospitalet | Copenhagen , Denmark, DK-2100Hôpital Necker-Enfants Malades - Centre de Référence des Maladies Héréditaires du Métabolisme | Paris , France, 75015Medical Genetics and Laboratory Diagnostics Center | Tbilisi , Georgia, 0159University Children's Hospital Hamburg Eppendorf (Kinder-UKE) Klinik für Kinder- und Jugendmedizin (Kinder-UKE) | Hamburg , Germany, 20246Universitätsklinikum Heidelberg / Zentrum für Kinder- und Jugendmedizin / Sektion für Neuropädiatrie & Stoffwechselmedizin | Heidelberg , Germany, 69120Universitätsklinikum Münster | Münster , Germany, 48149Azienda Ospedaliera-Universita Padova | Padua Veneto, Italy, 35129Department of Human Neuroscience, Child and Adolescent Neuropsychiatry, Policlinico Umberto I | Rome , Italy, 00185PTC Clinical Site 1 | Multiple Locations , Japan, PTC Clinical Site 2 | Multiple Locations , Japan, PTC Clinical Site 3 | Multiple Locations , Japan, PanAmerican Clinical Research | Guadalajara Jalisco, Mexico, 44670UMCG Beatrix Children's Hospital | Groningen , Netherlands, 9713 GZPomorski Uniwersytet Medyczny w Szczecinie Centrum Wsparcia Badań Klinicznych | Szczecin , Poland, 71-252CENTRO HOSPITALAR UNIVERSITÁRIO LISBOA NORTE Hospital de Santa Maria, | Lisbon Estremadura, Portugal, 1649-035CENTRO HOSPITALAR UNIVERSITÁRIO LISBOA NORTE Hospital de Santa Maria | Lisbon Estremadura, Portugal, 1649-035Centro Hospitalar Universitário Do Porto, Epe | Porto , Portugal, 4099-001Univerzitetni klinicni center Ljubljana | Ljubljana , Slovenia, 1000Hospital Sant Joan de Déu | Barcelona Esplugues de Llobregat, Spain, 08950Hospital Universitario Ramón y Cajal | Madrid , Spain, 28034Hospital Universitario Virgen del Rocío | Seville , Spain, 41013Hacettepe University Medical Faculty | Altındağ Ankara, Turkey (Türkiye), 06230Gazi Üniversitesi Tıp Fakültesi | Yenimahalle Ankara, Turkey (Türkiye), 06500İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi | Fatih Istanbul, Turkey (Türkiye), 34098Ege University Faculty of Medicine Children Hospital | Bornova İzmir, Turkey (Türkiye), 35100Çukurova Üniversitesi Tıp Fakültesi Balcalı Hastanesi | Adana , Turkey (Türkiye), 01330Birmingham Children's Hospital NHS Foundation Trust | Birmingham , United Kingdom, B4 6NHUNIVERSITY HOSPITALS BIRMINGHAM NHS Foundation Trust | Birmingham , United Kingdom, Great Ormond Street Hospital | London , United Kingdom, WC1N 3JH