Long-term JNT-517 treatment for people with phenylketonuria

An Open-Label Study to Evaluate the Long-Term Safety of JNT-517 in Participants With Phenylketonuria

This trial tests the long-term safety of JNT-517 in children and adults with PKU, including people who previously took JNT-517 and those who are new to the drug.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 240 (estimated)
• Ages: 4 Years and up
• Sex: All
• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry-sponsored)
• Locations: 12 sites (Gainesville, Florida and 11 other locations)
• Trial ID: NCT06628128 on ClinicalTrials.gov

What this trial studies

This Phase 3, open-label extension enrolls participants aged 4 and older to receive JNT-517 using age- and weight-banded dosing regardless of prior JNT-517 exposure. The primary aim is to collect long-term safety and tolerability data while participants maintain a consistent phenylalanine (Phe) diet, with protocol-specified pregnancy testing and medication restrictions. Eligible participants include those who completed earlier JNT-517 studies as well as study-naïve individuals, and stable dosing of other PKU treatments is allowed per protocol. Study visits occur at selected U.S. academic centers and results will inform the safety profile of chronic JNT-517 use across pediatric and adult populations.

Who should consider this trial

Good fit: People aged 4 years and older with confirmed PAH-deficiency PKU who weigh at least 12.5 kg, can maintain a consistent Phe diet, are not recently on pegvaliase or sepiapterin, are stable on any sapropterin or large neutral amino acids if used, and (for women of childbearing potential) agree to required pregnancy testing and contraception.

Not a fit: Patients under 4 years old, under 12.5 kg, currently on excluded medications, pregnant or unwilling to follow pregnancy precautions, or unable to attend required clinic visits are unlikely to be eligible or to benefit from participation.

Why it matters

Potential benefit: If successful, JNT-517 could become a safe long-term treatment option that helps control blood phenylalanine levels and reduce the burden of strict dietary management.

How similar studies have performed: Earlier JNT-517 studies (JNT517-101 and JNT517-201) have been conducted and this extension builds on their safety data, but large-scale long-term efficacy and safety across broader populations remain limited.

Eligibility criteria

Key Inclusion Criteria:

1. Diagnosis of phenylketonuria (ie, PAH deficiency) by either molecular testing or biochemical criteria consistent with the applicable regional guidelines.
2. Participants 4 years of age and older, inclusive, at time of Screening.
3. Not on pegvaliase within 4 weeks of Screening.
4. Not on sepiapterin within 2 weeks of Screening.
5. If on sapropterin or large neutral amino acids at Screening, must be on a stable dose for 4 weeks prior to Screening.
6. Willing and able to maintain a diet consistent in Phe content from the Screening period through the duration of the study, unless otherwise directed by a dietician as allowed in the protocol.
7. Body weight ≥ 12.5 kg.
8. If female of childbearing potential:

   1. Must have a negative serum pregnancy test at Screening and a negative urine pregnancy test by Day 1.
   2. Must practice sexual abstinence, or if involved in any sexual intercourse that could lead to pregnancy, must agree to use 2 different contraceptive methods, where at least 1 method must be highly effective, from Screening until at least 30 days after the last study drug administration.
   3. Must refrain from donating ova during the course of the study and for 30 days after the last dose of the study drug.
9. Is a female not of childbearing potential or postmenopausal, defined as follows:

   1. Has had surgical sterilization (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy).
   2. Has had amenorrhea for minimum of 1 year with confirmation by levels of follicle stimulating hormone testing.
   3. Has not achieved menarche (has not had first menstrual period). If a female achieves menarche during the study, she will need to follow the contraception requirement for females of childbearing potential.
10. If male, must practice sexual abstinence, or if involved in any sexual intercourse that could lead to pregnancy, must agree to use 2 different contraceptive methods, where at least 1 method must be highly effective, from Day 1 until at least 30 days after the last study drug administration and must refrain from donating sperm during the course of the study and for 30 days after the last dose of the study drug.

    Note: No restrictions are required for males who have undergone a documented vasectomy at least 4 months prior to Screening. If the vasectomy procedure is not documented or was performed less than 4 months prior to Screening, males must follow the same contraception as for non-vasectomized participants.
11. Capable of giving signed informed consent, or parent/legal guardian to provide informed consent and pediatric participant to give assent, and be able to comply with study procedures.
12. Participants with psychiatric illness must be well-controlled for the last 3 months prior to screening visit and, if on medication, on stable medications for the last 3 months.

Key Exclusion Criteria:

1. Participation in this study is not considered safe and/or feasible in the opinion of the Investigator.
2. Participants have not completed a previous JNT-517 study and are eligible for another active JNT-517 trial at the site, unless approval is obtained from the medical monitor.
3. Any acute or chronic medical condition that would prevent the participant from complying with the procedures or place the participant at risk if they participate in the study.
4. Positive for hepatitis B or C or human immunodeficiency virus.
5. Any history of significant liver disease.
6. Any history of cataracts or more than minimal cataracts observed during the Screening ophthalmologic examination.
7. Any surgical or medical conditions that may affect study drug absorption, distribution, metabolism, or excretion.
8. Estimated glomerular filtration rate \< 60 milliliters per minute per 1.73 square meters (mL/min/1.73 m\^2) by 2021 Chronic Kidney Disease Epidemiology Collaboration formula (participants aged 17 years or greater) or by Schwartz formula (participants aged 4 to 16 years of age).
9. History of drug or alcohol abuse in the last year.
10. Use of any medication that are inhibitors or inducers of cytochrome P450 (CYP)3A4 or inhibitors of the transporter P glycoprotein (P-gp) within 4 weeks prior to the first dose of study drug and unwilling and/or unable to avoid these medications throughout the treatment duration.
11. Use of any medications that are a substrate of breast cancer resistance protein (BCRP), multidrug and toxin extrusion (MATE)1, MATE2-K, organic anion transporter 3 (OAT3), or CYP3A4 within 4 weeks prior to the first dose of study drug and unwilling and/or unable to avoid these medications throughout the treatment duration (Appendix A). CYP3A4 substrates may be allowed if reduction in exposure is not expected to impact safety of the participant after consultation with the Medical Monitor.

    NOTE: Participants of childbearing potential will be permitted to continue with estrogen- or progesterone based oral contraceptives, but must agree to use 2 other methods of contraception, where at least 1 must be highly effective, or must agree to sexual abstinence during the study.
12. Current, recent, or suspected infection within 2 weeks of Screening of Severe Acute Respiratory Syndrome Coronavirus 2/Coronavirus Disease 2019 (SARS-CoV-2/COVID-19).
13. Unable to tolerate oral medication or inability to swallow tablets.
14. Allergy to JNT-517 or any component of the investigational product.
15. Any of the following laboratory values at the Screening visit:

    1. Alanine aminotransferase or aspartate aminotransferase values ˃ 1.5 x the upper limit of normal (ULN).
    2. Total bilirubin ˃ULN unless history of Gilbert Syndrome and then total bilirubin \>4 milligrams per deciliter \[mg/dL\] is exclusionary.
    3. Hemoglobin ˂10.0 g/dL (˂100.0 grams per liter \[g/L\])
    4. White blood cell count ˃1 x ULN
    5. Platelet count ˂150 × 109/L (˂150,000/cubic millimeters\[mm\^3\])
16. Participation in another investigational drug trial within 30 days (other than for JNT-517) or, if known 5 half-lives of investigational drug (whichever is longer).

Where this trial is running

Gainesville, Florida and 11 other locations

• University of Florida (UF) Health Shands Hospital — Gainesville, Florida, United States (Recruiting)
• University of South Florida — Tampa, Florida, United States (Recruiting)
• Oregon Health and Science University — Portland, Oregon, United States (Recruiting)
• University of Pittsburgh Medical Center (UPMC) - Children's Hospital of Pittsburgh — Pittsburgh, Pennsylvania, United States (Recruiting)
• Children's Medical Center Dallas — Dallas, Texas, United States (Recruiting)
• University of Texas Southwestern Medical Center — Dallas, Texas, United States (Recruiting)
• University of Texas Health (UTHealth) Science Center at Houston — Houston, Texas, United States (Recruiting)
• Utah Health - The University of Utah Hospital — Salt Lake City, Utah, United States (Recruiting)
• Children's Health Queensland - Queensland Children's Hospital — South Brisbane, Queensland, Australia (Recruiting)
• Mater Health - Mater Hospital Brisbane — South Brisbane, Queensland, Australia (Recruiting)
• Royal Adelaide Hospital — Adelaide, South Australia, Australia (Recruiting)
• Murdoch Children's Research Institute — Parkville, Victoria, Australia (Recruiting)

Study contacts

• Study coordinator: Otsuka Call Center

Conditions Phenylketonuria; PKU