Phenylketonuria Clinical Trial
Official title:
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.
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. |
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 |
Lead Sponsor | Collaborator |
---|---|
PTC Therapeutics |
United States, Australia, Brazil, Canada, Denmark, Georgia, Germany, Italy, Japan, Mexico, Netherlands, Portugal, Spain, Turkey, United Kingdom,
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 |
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