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

Phenylketonuria Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05166161
• Other study ID #: PTC923-MD-004-PKU
• Secondary ID: 2021-000497-28
• Status: Recruiting
• Phase: Phase 3
• Start date: February 14, 2022
• Est. completion date: February 7, 2025

Study information

• Verified date: April 2024
• Source: PTC Therapeutics
• Contact: Patient Advocacy
• Phone: 1-866-562-4620
• Email: medinfo[@]ptcbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Eligible participants are: Feeder participants: those who have completed a Phase 3 PTC Therapeutics (PTC) sponsored feeder study (including Study PTC923-MD-003-PKU). 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: February 7, 2025
• Est. primary completion date: February 7, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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 sponsor, 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 sponsor, 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.

Related Conditions & MeSH terms

• Phenylketonuria
• Phenylketonurias

Intervention

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

Locations

Country	Name	City	State
Australia	PARC Clinical Research	Adelaide	South Australia
Australia	Royal Children's Hospital	Parkville	Victoria
Australia	Westmead Hospital	Westmead	New South Wales
Brazil	Hospital de clinicas de Porto Alegre	Porto Alegre	Rio Grande Do Sul
Brazil	Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo	Ribeirão Preto	São Paulo
Canada	Metabolics and Genetics in Calgary (MAGIC) Clinic, Ltd.	Calgary	Alberta
Canada	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
Denmark	Copenhagen University Hospital, Rigshospitalet	Copenhagen
Georgia	Pediatric Surgery Center	Tbilisi
Germany	University Children's Hospital Hamburg Eppendorf (Kinder-UKE) Klinik für Kinder- und Jugendmedizin (Kinder-UKE)	Hamburg
Germany	Universitätsklinikum Heidelberg / Zentrum für Kinder- und Jugendmedizin / Sektion für Neuropädiatrie & Stoffwechselmedizin	Heidelberg
Germany	Universitätsklinikum Münster	Münster
Italy	Azienda Ospedaliera-Universita Padova	Padua	Veneto
Italy	Department of Human Neuroscience, Child and Adolescent Neuropsychiatry, Policlinico Umberto I	Rome
Japan	PTC Clinical Site	Multiple Locations
Mexico	PanAmerican Clinical Research	Guadalajara	Jalisco
Netherlands	UMCG Beatrix Children's Hospital	Groningen
Portugal	CENTRO HOSPITALAR UNIVERSITÁRIO LISBOA NORTE Hospital de Santa Maria	Lisboa	Estremadura
Portugal	CENTRO HOSPITALAR UNIVERSITÁRIO LISBOA NORTE Hospital de Santa Maria,	Lisboa	Estremadura
Portugal	Centro Hospitalar Universitário Do Porto, Epe	Porto	Douro Litoral
Spain	Hospital Sant Joan de Déu	Barcelona	Esplugues De Llobregat
Spain	Hospital Universitario Ramón y Cajal	Madrid
Turkey	Cukurova Üniversity Balcali Hospital Health Application and Research Center	Adana
Turkey	Hacettepe University Medical Faculty	Altindag	Ankara
Turkey	Ege University Faculty of Medicine Children Hospital	Bornova	Izmir
Turkey	Istanbul Üniversitesi Cerrahpasa Tip Fakültesi	Fatih	Istanbul
Turkey	Gazi Üniversitesi Tip Fakültesi	Yenimahalle	Ankara
United Kingdom	Birmingham Children's Hospital NHS Foundation Trust	Birmingham
United Kingdom	Great Ormond Street Hospital	London
United States	University of Colorado and the Children's Hospital CO	Aurora	Colorado
United States	Boston Children's Hospital	Boston	Massachusetts
United States	UF College of Medicine, Department of Pediatrics Division of Genetics and Metabolism	Gainesville	Florida
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	Icahn School of Medicine at Mount Sinai (ISMMS)	New York	New York
United States	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of Utah, Division of Medical Genetics (pediatric and adult clinic)	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
PTC Therapeutics

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Canada,  Denmark,  Georgia,  Germany,  Italy,  Japan,  Mexico,  Netherlands,  Portugal,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 approximately 2.5 years)
Primary	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	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 =18 years Adult PKU-QOL).	Baseline, Months 8, 14, 20, 26, 32, and 38
Secondary	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 ([=16 years]).	Baseline, Months 8, 14, 20, 26, 32, and 38