A Study of PTC923 in Participants With Phenylketonuria

NCT ID: NCT05099640

Last Updated: 2024-01-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 157 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-30
• Study Completion Date: 2023-05-03

Brief Summary

The main purpose of this trial is to evaluate the efficacy of PTC923 in reducing blood phenylalanine (Phe) levels in participants with phenylketonuria as measured by mean change in blood Phe levels from baseline to Weeks 5 and 6 (that is, the average of each respective treatment dose 2-week period of double-blind treatment).

Detailed Description

The study includes 2 parts: Part 1 and 2. Part 1 of the study tests for responsiveness to PTC923, with 14 days of open-label treatment with PTC923. At the end of treatment in Part 1, the mean change in blood Phe levels over the 14-day treatment period for all participants will be assessed against their pretreatment (baseline) blood Phe level. Participants ≥2 years of age who experience a <15% reduction in blood Phe levels will be classified as non-responsive and participation in the study will be terminated. Participants (≥2 years of age) who experience a ≥15% reduction in blood Phe levels will continue into Part 2. Participants <2 years of age who experience ≥15% reduction in blood Phe levels will be offered the option to enroll directly into an open-label extension Study PTC923-MD-004-PKU. Participants <2 years of age who experience a <15% reduction in blood Phe levels will be classified as nonresponsive, and participation in the study will be terminated. Following the minimum 14-day PTC923 washout period, all eligible participants will be randomized in Part 2 to receive either PTC923 or placebo. After 6 weeks of treatment with either PTC923 or placebo, participants will be offered the option to enter an open-label extension Study PTC923-MD-004-PKU (NCT05166161).

Conditions

Phenylketonuria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Part 1: PTC923

Participants will receive PTC923 7.5 milligrams (mg)/kilogram (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 14 days.

Group Type: EXPERIMENTAL

PTC923

Intervention Type: DRUG

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

Part 2: PTC923

Participants will receive PTC923 20 mg/kg daily for Weeks 1 and 2, then PTC923 40 mg/kg daily for Weeks 3 and 4, then PTC923 60 mg/kg daily for Weeks 5 and 6.

Group Type: EXPERIMENTAL

PTC923

Intervention Type: DRUG

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

Part 2: Placebo

Participants will receive equivalent quantities of placebo to match the 20 to 40 to 60 mg/kg dose escalation of the PTC923 treatment arm.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo matching to PTC923

Interventions

PTC923

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

Intervention Type: DRUG

Placebo

Placebo matching to PTC923

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Uncontrolled blood Phe level ≥360 μmol/L on current therapy anytime during screening and uncontrolled blood Phe level ≥360 μmol/L on current therapy when taking the average of the 3 most recent Phe levels from the participant's medical history (inclusive of the screening value).
• Clinical diagnosis of phenylketonuria 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 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.

Exclusion Criteria

• 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 tetrahydrobiopterin (BH4) or sepiapterin.
• Current participation in any other investigational drug study or use of any investigational agent within 30 days prior to screening.
• Any clinically significant laboratory abnormality as determined by the investigator.
• 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]) and/or under care of a nephrologist.
• Any abnormal physical examination and/or laboratory findings indicative of signs or symptoms of renal disease, including calculated GFR <60 mL/min/1.73 square meter (m^2).
• Requirement for concomitant treatment with any drug known to inhibit folate synthesis (for example, methotrexate).
• Confirmed diagnosis of a primary BH4 deficiency as evidenced by biallelic pathogenic mutations in 6-pyruvoyltetrahydropterin synthase, recessive guanosine-5'-triphosphate (GTP) cyclohydrolase I, sepiapterin reductase, quinoid dihydropteridine reductase, or pterin-4-alpha-carbinolamine dehydratase genes.
• Major surgery within the prior 90 days of screening.
• Concomitant treatment with BH4 supplementation (for example, sapropterin dihydrochloride, KUVAN) or pegvaliase-pqpz (PALYNZIQ).
• Unwillingness to washout from BH4 supplementation (for example, sapropterin dihydrochloride, KUVAN) or pegvaliase-pqpz (PALYNZIQ)

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PTC Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Stanford University Center for Academic Medicine

Stanford, California, United States

University of Colorado and the Children's Hospital CO

Aurora, Colorado, 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

Boston Children's Hospital

Boston, Massachusetts, United States

Icahn School of Medicine at Mount Sinai (ISMMS)

New York, New York, United States

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Children's Medical Center Dallas

Dallas, Texas, United States

University of Texas Health Science Center of Texas

Houston, Texas, United States

University of Utah, Division of Medical Genetics (pediatric and adult clinic)

Salt Lake City, Utah, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Westmead Hospital

Westmead, New South Wales, Australia

PARC Clinical Research

Adelaide, South Australia, Australia

Royal Melbourne Hospital

Melbourne, Victoria, Australia

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, Brazil

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, Canada

Copenhagen University Hospital, Rigshospitalet

Copenhagen, , Denmark

Bretonneau Hospital - CHRU de Tours

Tours, Centre-Val de Loire, France

CHRU de Tours- Hôpital Pédiatrique de Clocheville

Tours, Centre-Val de Loire, France

Pediatric Surgery Center

Tbilisi, , Georgia

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, , Germany

Policlinico Umberto I

Rome, Lazio, Italy

Division of Inherited Metabolic Diseases, Azienda Ospedaliera-Università Padova

Padua, Veneto, Italy

PanAmerican Clinical Research

Guadalajara, Jalisco, Mexico

Grupo Médico Camino SC

Benito Juárez, Mexico City, Mexico

UMCG Beatrix Children's Hospital

Groningen, , Netherlands

Centro Hospitalar Universitário Do Porto, Epe

Porto, Douro Litoral, Portugal

CENTRO HOSPITALAR UNIVERSITÁRIO LISBOA NORTE Hospital de Santa Maria,

Lisbon, Estremadura, Portugal

CENTRO HOSPITALAR UNIVERSITÁRIO LISBOA NORTE Hospital de Santa Maria

Lisbon, Estremadura, Portugal

Hospital Sant Joan de Déu

Barcelona, Esplugues de Llobregat, Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Hacettepe University Medical Faculty

Altındağ, Ankara, Turkey (Türkiye)

Gazi Üniversitesi Tıp Fakültesi

Yenimahalle, Ankara, Turkey (Türkiye)

İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi

Fatih, Istanbul, Turkey (Türkiye)

Ege University Faculty of Medicine Children Hospital

Bornova, İzmir, Turkey (Türkiye)

Cukurova Üniversity Balcali Hospital Health Application and Research Center

Adana, , Turkey (Türkiye)

Birmingham Children's Hospital NHS Foundation Trust

Birmingham, , United Kingdom

Great Ormond Street Hospital

London, , United Kingdom

Countries

United States; Australia; Brazil; Canada; Denmark; France; Georgia; Germany; Italy; Mexico; Netherlands; Portugal; Spain; Turkey (Türkiye); United Kingdom

References

Muntau AC, Longo N, Ezgu F, Schwartz IVD, Lah M, Bratkovic D, Margvelashvili L, Kiykim E, Zori R, Campistol Plana J, Belanger-Quintana A, Lund A, Guilder L, Chakrapani A, Mungan HN, Guimas A, Cabrales Guerra IDC, MacDonald A, Ingalls K, Smith N; APHENITY study group. Effects of oral sepiapterin on blood Phe concentration in a broad range of patients with phenylketonuria (APHENITY): results of an international, phase 3, randomised, double-blind, placebo-controlled trial. Lancet. 2024 Oct 5;404(10460):1333-1345. doi: 10.1016/S0140-6736(24)01556-3.

Reference Type: DERIVED

PMID: 39368841 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2021-000474-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

PTC923-MD-003-PKU

Identifier Type: -

Identifier Source: org_study_id