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

April 22, 2026 updated by: PTC Therapeutics

A Phase 3 Open-Label Study of PTC923 (Sepiapterin) in Phenylketonuria

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed 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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
200

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Australia
    • Brisbane
      • South Brisbane, Brisbane, Australia
        • The Queensland Children's Hospital
    • New South Wales
      • Westmead, New South Wales, Australia, 2145
        • Westmead Hospital
    • South Australia
      • Adelaide, South Australia, Australia, SA 5000
        • PARC Clinical Research
    • Victoria
      • Parkville, Victoria, Australia, 3052
        • Royal Children's Hospital
  • Brazil
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
        • Hospital de Clinicas de Porto Alegre
    • São Paulo
      • Ribeirão Preto, São Paulo, Brazil, 14051-140
        • Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto da Universidade de Sao Paulo
  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2E 7Z4
        • Metabolics and Genetics in Calgary (MAGIC) Clinic, Ltd.
    • Ontario
      • Hamilton, Ontario, Canada, L8N 3Z5
        • McMaster Children's Hospital Hamilton Health Sciences
      • Toronto, Ontario, Canada, M5G 1X8
        • 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
  • Czechia
      • Prague, Czechia, 100 34
        • Fakultní nemocnice Královské Vinohrady Klinika dětí a dorostu Ambulance pro léčbu PKU a HPA
  • Denmark
      • Copenhagen, Denmark, DK-2100
        • Copenhagen University Hospital, Rigshospitalet
  • France
      • Paris, France, 75015
        • Hôpital Necker-Enfants Malades - Centre de Référence des Maladies Héréditaires du Métabolisme
  • Georgia
      • Tbilisi, Georgia, 0159
        • Medical Genetics and Laboratory Diagnostics Center
  • Germany
      • Hamburg, Germany, 20246
        • University Children's Hospital Hamburg Eppendorf (Kinder-UKE) Klinik für Kinder- und Jugendmedizin (Kinder-UKE)
      • Heidelberg, Germany, 69120
        • Universitätsklinikum Heidelberg / Zentrum für Kinder- und Jugendmedizin / Sektion für Neuropädiatrie & Stoffwechselmedizin
      • Münster, Germany, 48149
        • Universitätsklinikum Münster
  • Italy
      • Rome, Italy, 00185
        • Department of Human Neuroscience, Child and Adolescent Neuropsychiatry, Policlinico Umberto I
    • Veneto
      • Padua, Veneto, Italy, 35129
        • Azienda Ospedaliera-Universita Padova
  • Japan
      • Multiple Locations, Japan
        • PTC Clinical Site 1
      • Multiple Locations, Japan
        • PTC Clinical Site 2
      • Multiple Locations, Japan
        • PTC Clinical Site 3
  • Mexico
    • Jalisco
      • Guadalajara, Jalisco, Mexico, 44670
        • PanAmerican Clinical Research
  • Netherlands
      • Groningen, Netherlands, 9713 GZ
        • UMCG Beatrix Children's Hospital
  • Poland
      • Szczecin, Poland, 71-252
        • Pomorski Uniwersytet Medyczny w Szczecinie Centrum Wsparcia Badań Klinicznych
  • Portugal
      • Porto, Portugal, 4099-001
        • Centro Hospitalar Universitario do Porto, EPE
    • Estremadura
      • Lisbon, Estremadura, Portugal, 1649-035
        • CENTRO HOSPITALAR UNIVERSITÁRIO LISBOA NORTE Hospital de Santa Maria,
      • Lisbon, Estremadura, Portugal, 1649-035
        • CENTRO HOSPITALAR UNIVERSITÁRIO LISBOA NORTE Hospital de Santa Maria
  • Slovenia
      • Ljubljana, Slovenia, 1000
        • Univerzitetni klinicni center Ljubljana
  • Spain
      • Madrid, Spain, 28034
        • Hospital Universitario Ramón y Cajal
      • Seville, Spain, 41013
        • Hospital Universitario Virgen del Rocio
    • Esplugues de Llobregat
      • Barcelona, Esplugues de Llobregat, Spain, 08950
        • Hospital Sant Joan de Déu
  • Turkey (Türkiye)
      • Adana, Turkey (Türkiye), 01330
        • Çukurova Üniversitesi Tıp Fakültesi Balcalı Hastanesi
    • Ankara
      • Altındağ, Ankara, Turkey (Türkiye), 06230
        • Hacettepe University Medical Faculty
      • Yenimahalle, Ankara, Turkey (Türkiye), 06500
        • Gazi Üniversitesi Tıp Fakültesi
    • Istanbul
      • Fatih, Istanbul, Turkey (Türkiye), 34098
        • İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi
    • İzmir
      • Bornova, İzmir, Turkey (Türkiye), 35100
        • Ege University Faculty of Medicine Children Hospital
  • United Kingdom
      • Birmingham, United Kingdom, B4 6NH
        • Birmingham Children's Hospital NHS Foundation Trust
      • Birmingham, United Kingdom
        • University Hospitals Birmingham NHS Foundation Trust
      • London, United Kingdom, WC1N 3JH
        • Great Ormond Street Hospital
  • United States
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Children's Hospital Colorado
    • Florida
      • Gainesville, Florida, United States, 32610
        • UF College of Medicine, Department of Pediatrics Division of Genetics and Metabolism
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University School of Medicine Department of Medical and Molecular Genetics
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Boston Children's Hospital
    • New York
      • New York, New York, United States, 10009
        • Icahn School of Medicine at Mount Sinai (ISMMS)
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15224
        • UPMC Children's Hospital of Pittsburgh
    • Utah
      • Salt Lake City, Utah, United States, 84108
        • University of Utah

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: 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.
Other Names:
  • Sepiapterin
  • Sephience

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in Dietary Phe/Protein Consumption at Week 26, Measured During Phe Tolerance Assessment Period
Time Frame: Baseline, Week 26
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
Number of Treatment-Emergent Adverse Events (TEAEs)
Time Frame: Baseline up to end of study (up to 4 years)
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)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change From Baseline in QOL Using the European Quality of Life - 5 Dimensions (EQ-5D) at Months 8, 14, 20, 26, 32, and 38
Time Frame: Baseline, 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 ([≥16 years]).
Baseline, Months 8, 14, 20, 26, 32, and 38
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
Time Frame: Baseline, 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 ≥18 years Adult PKU-QOL).
Baseline, Months 8, 14, 20, 26, 32, and 38
Palatability of PTC923
Time Frame: Month 1 Day 1
For participants <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)?
Month 1 Day 1
Acceptability/Ease of Administration of PTC923
Time Frame: Month 1 Day 1
For all participants <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).
Month 1 Day 1
Taste/Flavor Assessment Using a Facial Hedonic Scale
Time Frame: Month 1 Day 1
For participants ≥5 to <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).
Month 1 Day 1
Plasma Sepiapterin Concentration
Time Frame: Month 1 Day 1 up to Month 11 Day 1
Month 1 Day 1 up to Month 11 Day 1
Plasma BH4 Concentration
Time Frame: Month 1 Day 1 up to Month 11 Day 1
Month 1 Day 1 up to Month 11 Day 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
PTC Therapeutics

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 14, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 30, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 8, 2021

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 8, 2021

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 21, 2021

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 24, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 22, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • PTC923-MD-004-PKU
  • 2021-000497-28 (EudraCT Number)
  • 2023-509229-31-00 (Other Identifier: CTIS Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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