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Long-term safety evaluation of PTC923 for phenylketonuria

A Phase 3 Open-Label Study of PTC923 (Sepiapterin) in Phenylketonuria

Phase 3 Interventional PTC Therapeutics · NCT05166161

This study tests the long-term safety of a medication called PTC923 for people with phenylketonuria (PKU) to see how it affects their diet and health.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment200 (estimated)
SexAll
SponsorPTC Therapeutics Industry-sponsored
Drugs / interventionsmethotrexate
Locations45 sites (Aurora, Colorado and 44 other locations)
Trial IDNCT05166161 on ClinicalTrials.gov

What this trial studies

This study evaluates the long-term safety of PTC923 in individuals diagnosed with phenylketonuria (PKU). Participants include those who have previously completed a feeder study and those who have not, categorized based on their blood phenylalanine levels. The study aims to assess changes in dietary phenylalanine and protein consumption from baseline. Participants are required to maintain their current diet unless instructed otherwise by the investigator.

Who should consider this trial

Good fit: Ideal candidates include individuals with a clinical diagnosis of PKU and specific blood phenylalanine levels.

Not a fit: Patients who are unable to tolerate oral medication or are pregnant or breastfeeding may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide a safer treatment option for patients with phenylketonuria.

How similar studies have performed: Previous studies have shown promise in evaluating treatments for PKU, but the long-term safety of PTC923 specifically is being assessed for the first time.

Eligibility criteria

Show full inclusion / exclusion 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.

Where this trial is running

Aurora, Colorado and 44 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Phenylketonuria
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.