Clinical trial NCT05166161: A Long-Term Safety Study of PTC923 in Participants With Phenylketonuria
Official title: A Phase 3 Open-Label Study of PTC923 (Sepiapterin) in Phenylketonuria
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Phenylketonuria
Lead sponsor: PTC Therapeutics
Sponsor class: INDUSTRY
First posted: 2021-12-21
Enrollment: 200
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to end of study (up to 4 years)
measure: Change From Baseline in Dietary Phe/Protein Consumption at Week 26, Measured During Phe Tolerance Assessment Period
timeFrame: Baseline, Week 26
Secondary outcomes:
measure: 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
timeFrame: Baseline, Months 8, 14, 20, 26, 32, and 38
measure: Change From Baseline in QOL Using the European Quality of Life - 5 Dimensions (EQ-5D) at Months 8, 14, 20, 26, 32, and 38
timeFrame: Baseline, Months 8, 14, 20, 26, 32, and 38
measure: Palatability of PTC923
timeFrame: Month 1 Day 1
measure: Acceptability/Ease of Administration of PTC923
timeFrame: Month 1 Day 1
measure: Taste/Flavor Assessment Using a Facial Hedonic Scale
timeFrame: Month 1 Day 1
measure: Plasma Sepiapterin Concentration
timeFrame: Month 1 Day 1 up to Month 11 Day 1
measure: Plasma BH4 Concentration
timeFrame: Month 1 Day 1 up to Month 11 Day 1
Other outcomes:
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Gainesville
country: United States
facility: UF College of Medicine, Department of Pediatrics Division of Genetics and Metabolism
state: Florida
city: Indianapolis
country: United States
facility: Indiana University School of Medicine Department of Medical and Molecular Genetics
state: Indiana
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai (ISMMS)
state: New York
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Adelaide
country: Australia
facility: PARC Clinical Research
state: South Australia
city: Parkville
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Porto Alegre
country: Brazil
facility: Hospital de clinicas de Porto Alegre
state: Rio Grande Do Sul
city: Ribeirão Preto
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
state: São Paulo
city: Calgary
country: Canada
facility: Metabolics and Genetics in Calgary (MAGIC) Clinic, Ltd.
state: Alberta
city: Hamilton
country: Canada
facility: McMaster Children's Hospital Hamilton Health Sciences
state: Ontario
city: Toronto
country: Canada
facility: 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
state: Ontario
city: Prague
country: Czechia
facility: Fakultní nemocnice Královské Vinohrady Klinika dětí a dorostu Ambulance pro léčbu PKU a HPA
city: Copenhagen
country: Denmark
facility: Copenhagen University Hospital, Rigshospitalet
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades - Centre de Référence des Maladies Héréditaires du Métabolisme
city: Tbilisi
country: Georgia
facility: Medical Genetics and Laboratory Diagnostics Center
city: Hamburg
country: Germany
facility: University Children's Hospital Hamburg Eppendorf (Kinder-UKE) Klinik für Kinder- und Jugendmedizin (Kinder-UKE)
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg / Zentrum für Kinder- und Jugendmedizin / Sektion für Neuropädiatrie & Stoffwechselmedizin
city: Münster
country: Germany
facility: Universitätsklinikum Münster
city: Padua
country: Italy
facility: Azienda Ospedaliera-Universita Padova
state: Veneto
city: Rome
country: Italy
facility: Department of Human Neuroscience, Child and Adolescent Neuropsychiatry, Policlinico Umberto I
city: Multiple Locations
country: Japan
facility: PTC Clinical Site 1
city: Multiple Locations
country: Japan
facility: PTC Clinical Site 2
city: Multiple Locations
country: Japan
facility: PTC Clinical Site 3
city: Guadalajara
country: Mexico
facility: PanAmerican Clinical Research
state: Jalisco
city: Groningen
country: Netherlands
facility: UMCG Beatrix Children's Hospital
city: Szczecin
country: Poland
facility: Pomorski Uniwersytet Medyczny w Szczecinie Centrum Wsparcia Badań Klinicznych
city: Lisboa
country: Portugal
facility: CENTRO HOSPITALAR UNIVERSITÁRIO LISBOA NORTE Hospital de Santa Maria,
state: Estremadura
city: Lisboa
country: Portugal
facility: CENTRO HOSPITALAR UNIVERSITÁRIO LISBOA NORTE Hospital de Santa Maria
state: Estremadura
city: Porto
country: Portugal
facility: Centro Hospitalar Universitário Do Porto, Epe
city: Ljubljana
country: Slovenia
facility: Univerzitetni klinicni center Ljubljana
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Déu
state: Esplugues De Llobregat
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Altındağ
country: Turkey
facility: Hacettepe University Medical Faculty
state: Ankara
city: Yenimahalle
country: Turkey
facility: Gazi Üniversitesi Tıp Fakültesi
state: Ankara
city: Fatih
country: Turkey
facility: İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi
state: Istanbul
city: Bornova
country: Turkey
facility: Ege University Faculty of Medicine Children Hospital
state: Izmir
city: Adana
country: Turkey
facility: Çukurova Üniversitesi Tıp Fakültesi Balcalı Hastanesi
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital NHS Foundation Trust
city: Birmingham
country: United Kingdom
facility: UNIVERSITY HOSPITALS BIRMINGHAM NHS Foundation Trust
city: London
country: United Kingdom
facility: Great Ormond Street Hospital
Study officials:
References: