A Study of PTC923 in Participants With Phenylketonuria

NCT05099640 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: PTC923-MD-003-PKU2021-000474-29
• Study Type: interventional
• Target: 157
• Locations: 15 countries
• Sites: 43

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).

Conditions

Phenylketonuria

Outcome Measures

Primary Outcomes (2)

• Part 2 Double-blind Phase: Mean Change From Baseline in Blood Phenylketonuria (Phe) Level to Weeks 5 and 6 (Averaged Over a 2-week Period) in Participants With Phe Reduction From Baseline ≥30% During Part 1

  Baseline was defined as the average of Day -1 and Day 1 predose blood Phe levels in Part 2, and mean level at Weeks 5 and 6 was calculated as the average of blood Phe levels collected during the Week 5-6 analysis visit window. Least square (LS) mean and standard error (SE) were calculated using mixed model repeated measures (MMRM) method.

  Baseline, Weeks 5 and 6 (average of the 2-week period)

• Part 2 Double-blind Phase: Percent Change From Baseline in Blood Phe Level to Weeks 5 and 6 (Averaged Over a 2-week Period) in Participants With Phe Reduction From Baseline ≥30% During Part 1

  Baseline was defined as the average of Day -1 and Day 1 predose blood Phe levels in Part 2, and mean level at Weeks 5 and 6 was calculated as the average of blood Phe levels collected during the Week 5-6 analysis visit window. LS mean and SE were calculated using MMRM method.

  Baseline, Weeks 5 and 6 (average of the 2-week period)

Secondary Outcomes (8)

• Part 2 Double-blind Phase: Percentage of Participants With Baseline Phe Levels ≥600 μmol/L Who Achieved Phe Levels <600 μmol/L in Participants With Phe Reduction From Baseline ≥30% During Part 1

  Weeks 5 and 6 (average of the 2-week period)

• Part 2 Double-blind Phase: Percentage of Participants With Baseline Phe Levels ≥360 μmol/L Who Achieved Phe Levels <360 μmol/L in Participants With Phe Reduction From Baseline ≥30% During Part 1

  Weeks 5 and 6 (average of the 2-week period)

• Part 2 Double-blind Phase: Mean Change From Baseline in Blood Phe Level at Each 2-Week Period (Averaged Over Each 2-Week Period) in Participants With Phe Reduction From Baseline ≥30% During Part 1

  Baseline, Weeks 1 and 2, Weeks 3 and 4, and Weeks 5 and 6 (average of each 2-week period)

• Part 2 Double-blind Phase: Percent Change From Baseline in Blood Phe Level at Each 2-Week Period (Averaged Over Each 2-Week Period) in Participants With Phe Reduction From Baseline ≥30% During Part 1

  Baseline, Weeks 1 and 2, Weeks 3 and 4, and Weeks 5 and 6 (average of each 2-week period)

• Part 1 Open-label Run-in Phase: Plasma Concentration of Tetrahydrobiopterin (BH4) and Sepiapterin

  Predose, 0.5, 1, 2, 4, 6, 8, and 24 hours postdose at Day 1; 2 and 6 hours postdose at Day 14

Other Outcomes (4)

• Part 2 Double-blind Phase: Mean Change From Baseline in Blood Phe Level to Weeks 5 and 6 (Averaged Over a 2-week Period) in Classical PKU Participants With Phe Reduction From Baseline ≥30% During Part 1

  Baseline, Weeks 5 and 6 (average of the 2-week period)

• Part 2 Double-blind Phase: Percent Change From Baseline in Blood Phe Level to Weeks 5 and 6 (Averaged Over a 2-week Period) in Classical PKU Participants With Phe Reduction From Baseline ≥30% During Part 1

  Baseline, Weeks 5 and 6 (average of the 2-week period)

• Part 1 Open-label Run-in Phase: Mean Change From Baseline (Part 1) in Blood Phe Level to Weeks 1 and 2 (Averaged Over a 2-week Period) in Participants With Phe Reduction From Baseline ≥30% During Part 1

  Baseline (Part 1), Weeks 1 and 2 (average of the 2-week period)

Study Arms (3)

Part 1: PTC923

EXPERIMENTAL

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.

Drug: PTC923

Part 2: PTC923

EXPERIMENTAL

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.

Drug: PTC923

Part 2: Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

PTC923 DRUG

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

Part 1: PTC923; Part 2: PTC923

Placebo DRUG

Placebo matching to PTC923

Part 2: Placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• PTC Therapeutics: lead

Study Sites (43)

Stanford University Center for Academic Medicine

Stanford, California, 94304, United States

Location

University of Colorado and the Children's Hospital CO

Aurora, Colorado, 80045, United States

Location

UF College of Medicine, Department of Pediatrics Division of Genetics and Metabolism

Gainesville, Florida, 32608, United States

Location

Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Icahn School of Medicine at Mount Sinai (ISMMS)

New York, New York, 01009, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Children's Medical Center Dallas

Dallas, Texas, 75235, United States

Location

University of Texas Health Science Center of Texas

Houston, Texas, 77030, United States

Location

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

Salt Lake City, Utah, 84108, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

PARC Clinical Research

Adelaide, South Australia, SA 5000, Australia

Location

Royal Melbourne Hospital

Melbourne, Victoria, 3050, Australia

Location

Hospital de clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo

Ribeirão Preto, São Paulo, 14051-140, Brazil

Location

Metabolics and Genetics in Calgary (MAGIC) Clinic, Ltd.

Calgary, Alberta, AB T2M 0L6, Canada

Location

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, M5G 1X8, Canada

Location

Copenhagen University Hospital, Rigshospitalet

Copenhagen, DK-2100, Denmark

Location

Bretonneau Hospital - CHRU de Tours

Tours, Centre-Val de Loire, 37000, France

Location

CHRU de Tours- Hôpital Pédiatrique de Clocheville

Tours, Centre-Val de Loire, 37044, France

Location

Pediatric Surgery Center

Tbilisi, 159, Georgia

Location

University Children's Hospital Hamburg Eppendorf (Kinder-UKE) Klinik für Kinder- und Jugendmedizin (Kinder-UKE)

Hamburg, 20246, Germany

Location

Universitätsklinikum Heidelberg / Zentrum für Kinder- und Jugendmedizin / Sektion für Neuropädiatrie & Stoffwechselmedizin

Heidelberg, 69120, Germany

Location

Universitätsklinikum Münster

Münster, 48149, Germany

Location

Policlinico Umberto I

Rome, Lazio, 00185, Italy

Location

Division of Inherited Metabolic Diseases, Azienda Ospedaliera-Università Padova

Padua, Veneto, 35128, Italy

Location

PanAmerican Clinical Research

Guadalajara, Jalisco, 44670, Mexico

Location

Grupo Médico Camino SC

Benito Juárez, Mexico City, 3310, Mexico

Location

UMCG Beatrix Children's Hospital

Groningen, 9713 GZ, Netherlands

Location

Centro Hospitalar Universitário Do Porto, Epe

Porto, Douro Litoral, 4099-001, Portugal

Location

CENTRO HOSPITALAR UNIVERSITÁRIO LISBOA NORTE Hospital de Santa Maria,

Lisbon, Estremadura, 1649-035, Portugal

Location

CENTRO HOSPITALAR UNIVERSITÁRIO LISBOA NORTE Hospital de Santa Maria

Lisbon, Estremadura, 1649-035, Portugal

Location

Hospital Sant Joan de Déu

Barcelona, Esplugues de Llobregat, 8950, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hacettepe University Medical Faculty

Altındağ, Ankara, 6230, Turkey (Türkiye)

Location

Gazi Üniversitesi Tıp Fakültesi

Yenimahalle, Ankara, 6560, Turkey (Türkiye)

Location

İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi

Fatih, Istanbul, 34098, Turkey (Türkiye)

Location

Ege University Faculty of Medicine Children Hospital

Bornova, İzmir, 35100, Turkey (Türkiye)

Location

Cukurova Üniversity Balcali Hospital Health Application and Research Center

Adana, 1130, Turkey (Türkiye)

Location

Birmingham Children's Hospital NHS Foundation Trust

Birmingham, B4 6DH, United Kingdom

Location

Great Ormond Street Hospital

London, WC1N 3JH, United Kingdom

Location

Related Publications (2)

• Muntau AC, Gallagher S, Lah M, Belanger-Quintana A, Longo N. Sepiapterin as a treatment for people living with phenylketonuria: a plain language summary of the APHENITY trial. J Comp Eff Res. 2026 Jan;15(1):e250116. doi: 10.57264/cer-2025-0116. Epub 2025 Dec 9.

  PMID: 41363942 DERIVED

• 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.

  PMID: 39368841 DERIVED

MeSH Terms

Conditions

Phenylketonurias

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Patient Advocacy
• Organization: PTC Therapeutics, Inc.

medinfo@ptcbio.com

1-866-562-4620

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 6, 2021
• First Posted: October 29, 2021
• Study Start: September 30, 2021
• Primary Completion: April 3, 2023
• Study Completion: May 3, 2023
• Last Updated: January 10, 2024
• Results First Posted: January 10, 2024

Record last verified: 2023-12

Locations

AU (3); GE (1); US (12); IT (2); TU (5); PT (3); GB (2); ES (2); DK (1); BR (2); CA (2); DE (3); ME (2); FR (2); NL (1)