PhenylketonuriaPhase 3NCT05099640
A Study of PTC923 in Participants With Phenylketonuria
A Phase 3 study testing PTC923 in people with Phenylketonuria, run by PTC Therapeutics at 43 sites in 15 countries.
Trial 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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Phenylketonuria
- What is being tested?
- PTC923
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 157 participants
- Where
- 43 sitesin 15 countries
- Study dates
- 30 Sep 2021to 3 May 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 14Show fewer
- 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)
Trial locations and contacts
43 sites in 15 countries.
43 sites in 15 countries
United States12 sites
University of Colorado and the Children's Hospital CO
Aurora, Colorado, 80045
Boston Children's Hospital
Boston, Massachusetts, 02115
Children's Medical Center Dallas
Dallas, Texas, 75235
UF College of Medicine, Department of Pediatrics Division of Genetics and Metabolism
Gainesville, Florida, 32608
University of Texas Health Science Center of Texas
Houston, Texas, 77030
Indiana University School of Medicine
Indianapolis, Indiana, 46202
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Icahn School of Medicine at Mount Sinai (ISMMS)
New York, New York, 01009
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
University of Utah, Division of Medical Genetics (pediatric and adult clinic)
Salt Lake City, Utah, 84108
Stanford University Center for Academic Medicine
Stanford, California, 94304
Turkey (Türkiye)5 sites
Cukurova Üniversity Balcali Hospital Health Application and Research Center
Adana, 1130
Hacettepe University Medical Faculty
Altındağ, Ankara, 6230
Ege University Faculty of Medicine Children Hospital
Bornova, İzmir, 35100
İstanbul Üniversitesi Cerrahpaşa Tıp Fakültesi
Fatih, Istanbul, 34098
Gazi Üniversitesi Tıp Fakültesi
Yenimahalle, Ankara, 6560
Australia3 sites
PARC Clinical Research
Adelaide, South Australia, SA 5000
Royal Melbourne Hospital
Melbourne, Victoria, 3050
Westmead Hospital
Westmead, New South Wales, 2145
Germany3 sites
University Children's Hospital Hamburg Eppendorf (Kinder-UKE) Klinik für Kinder- und Jugendmedizin (Kinder-UKE)
Hamburg, 20246
Universitätsklinikum Heidelberg / Zentrum für Kinder- und Jugendmedizin / Sektion für Neuropädiatrie & Stoffwechselmedizin
Heidelberg, 69120
Universitätsklinikum Münster
Münster, 48149
Portugal3 sites
CENTRO HOSPITALAR UNIVERSITÁRIO LISBOA NORTE Hospital de Santa Maria,
Lisbon, Estremadura, 1649-035
CENTRO HOSPITALAR UNIVERSITÁRIO LISBOA NORTE Hospital de Santa Maria
Lisbon, Estremadura, 1649-035
Centro Hospitalar Universitário Do Porto, Epe
Porto, Douro Litoral, 4099-001
Brazil2 sites
Hospital de clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-903
Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo
Ribeirão Preto, São Paulo, 14051-140
Canada2 sites
Metabolics and Genetics in Calgary (MAGIC) Clinic, Ltd.
Calgary, Alberta, AB T2M 0L6
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
France2 sites
Bretonneau Hospital - CHRU de Tours
Tours, Centre-Val de Loire, 37000
CHRU de Tours- Hôpital Pédiatrique de Clocheville
Tours, Centre-Val de Loire, 37044
Italy2 sites
Division of Inherited Metabolic Diseases, Azienda Ospedaliera-Università Padova
Padua, Veneto, 35128
Policlinico Umberto I
Rome, Lazio, 00185
Mexico2 sites
Grupo Médico Camino SC
Benito Juárez, Mexico City, 3310
PanAmerican Clinical Research
Guadalajara, Jalisco, 44670
Spain2 sites
Hospital Sant Joan de Déu
Barcelona, Esplugues de Llobregat, 8950
Hospital Universitario Ramón y Cajal
Madrid, 28034
United Kingdom2 sites
Birmingham Children's Hospital NHS Foundation Trust
Birmingham, B4 6DH
Great Ormond Street Hospital
London, WC1N 3JH
Denmark1 site
Copenhagen University Hospital, Rigshospitalet
Copenhagen, DK-2100
About this study
Official title: A Phase 3 Study of PTC923 in Subjects With Phenylketonuria
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).
Read the 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
- Being tested
- PTC923, Placebo
- Medical subject headings
- Phenylketonurias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PTC923Drug
PTC923 powder for oral use will be suspended in water or apple juice prior to administration.
PlaceboDrug
Placebo matching to PTC923
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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
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.
Measured: 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
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.
Measured: 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 was defined as the average of Day -1 and Day 1 predose blood Phe levels in Part 2, and mean levels at Weeks 1 and 2, Weeks 3 and 4, and Weeks 5 and 6 were calculated as the average of blood Phe levels collected during the Week 1-2, Week 3-4, and Week 5-6 analysis visit windows, respectively.
Measured: 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 was defined as the average of Day -1 and Day 1 predose blood Phe levels in Part 2, and mean levels at Weeks 1 and 2, Weeks 3 and 4, and Weeks 5 and 6 were calculated as the average of blood Phe levels collected during the Week 1-2, Week 3-4, and Week 5-6 analysis visit windows, respectively.
Measured: 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
Measured: Predose, 0.5, 1, 2, 4, 6, 8, and 24 hours postdose at Day 1; 2 and 6 hours postdose at Day 14
Part 2 Double-blind Phase: Plasma Concentration of BH4 and Sepiapterin
Measured: Predose and 4 hours postdose at Days 1, 14, 28, and 42
Part 1 Open-label Run-in Phase: Area Under the Concentration-time Curve From Time 0 to 24 Hours Postdose (AUC0-24h) of Sepiapterin and BH4 Following the First Dose of Sepiapterin at 60 mg/kg
Measured: 0 to 24 hours postdose at Day 1
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. TEAEs were considered:
- Part 1 TEAEs, which included all AEs occurring after first dose in Part 1 but before first dose in Part 2;
- Part 2 TEAEs, which included all AEs after first randomized dose in Part 2. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Measured: Baseline up to Day 42
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2021
- Study start30 Sep 2021
- Primary completion3 Apr 2023
- Study completion3 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for PhenylketonuriaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 157 participants (actual)
Sponsor and investigators
- Lead sponsor
- PTC Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05099640
- Sponsor's protocol ID
- PTC923-MD-003-PKU
- Other IDs
- 2021-000474-29
- Status last verified
- Dec 2023
- First submitted
- 6 Oct 2021
- Last updated
- 10 Jan 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 41363942Muntau 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.
PubMed 39368841
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Study of PTC923 in Subjects With Phenylketonuria
- ClinicalTrials.gov ID
- NCT05099640
- Acronym / sponsor ID
- PTC923-MD-003-PKU
- Conditions
- Phenylketonuria
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 157 participants (actual)
- Lead sponsor
- PTC TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 30 Sep 2021 (actual)
- Primary completion
- 3 Apr 2023 (actual)
- Study completion
- 3 May 2023 (actual)
- First posted
- 29 Oct 2021 (actual)
- Results
- Posted 10 Jan 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part 1: PTC923 | Experimental | Drug: PTC923Participants 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. |
| Part 2: PTC923 | Experimental | Drug: PTC923Participants 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. |
| Part 2: Placebo | Placebo comparator | Drug: PlaceboParticipants will receive equivalent quantities of placebo to match the 20 to 40 to 60 mg/kg dose escalation of the PTC923 treatment arm. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PTC923PTC923 powder for oral use will be suspended in water or apple juice prior to administration. | Drug | Part 1: PTC923, Part 2: PTC923 |
| PlaceboPlacebo matching to PTC923 | Drug | Part 2: Placebo |
Primary outcome
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
Time frame: Baseline, Weeks 5 and 6 (average of the 2-week period)
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.
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
Time frame: Baseline, Weeks 5 and 6 (average of the 2-week period)
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.
8 secondary outcomes
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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Predose, 0.5, 1, 2, 4, 6, 8, and 24 hours postdose at Day 1; 2 and 6 hours postdose at Day 14
Part 2 Double-blind Phase: Plasma Concentration of BH4 and Sepiapterin
Time frame: Predose and 4 hours postdose at Days 1, 14, 28, and 42
Part 1 Open-label Run-in Phase: Area Under the Concentration-time Curve From Time 0 to 24 Hours Postdose (AUC0-24h) of Sepiapterin and BH4 Following the First Dose of Sepiapterin at 60 mg/kg
Time frame: 0 to 24 hours postdose at Day 1
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: Baseline up to Day 42
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41363942Muntau 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.
- Derived from this study: PubMed 39368841Muntau 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
43 sites in 15 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing PTC923 in people with Phenylketonuria, run by PTC Therapeutics at 43 sites in 15 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 43 sites in United States, Turkey (Türkiye), Australia, Germany, Portugal and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jan 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: Baseline, Weeks 5 and 6 (average of the 2-week period)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05099640, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2024.