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JNT-517 treatment for adults with phenylketonuria (PKU)

A Phase 3, Double-Blind, Randomized, Two-Period, Multicenter, Placebo-Controlled, Efficacy and Safety Study of JNT-517 for the Treatment of Participants With Phenylketonuria

Phase 3 Interventional Otsuka Pharmaceutical Development & Commercialization, Inc. · NCT06971731

This study will test whether taking JNT-517 pills twice daily lowers high blood phenylalanine and is safe for adults with PKU.

Quick facts

PhasePhase 3
Study typeInterventional
Enrollment120 (estimated)
Ages18 Years and up
SexAll
SponsorOtsuka Pharmaceutical Development & Commercialization, Inc. Industry-sponsored
Locations25 sites (Los Angeles, California and 24 other locations)
Trial IDNCT06971731 on ClinicalTrials.gov

What this trial studies

This Phase 3, randomized, double-blind study gives adults with PKU either JNT-517 or placebo for an initial ~6-week blinded period with about a 2 in 3 chance of receiving active drug. After that, participants who continue will receive one of two JNT-517 doses for an additional 46 weeks, and total participation can last up to ~400 days including screening. Dosing is oral JNT-517 75 mg or 150 mg twice daily (BID) or matching placebo, with clinic visits or mobile nurse home visits for monitoring, safety labs, and pharmacokinetic sampling. The study requires dietary stabilization and multiple fasting plasma phenylalanine measurements during screening to confirm eligibility and stable dietary intake.

Who should consider this trial

Good fit: Adults aged 18 or older with a clinical diagnosis of PKU and an average of at least three fasting plasma phenylalanine measurements ≥360 μmol/L who can maintain a stable Phe/protein diet and meet other medication stability requirements are the intended participants.

Not a fit: People with well-controlled phenylalanine levels below the eligibility threshold, pregnant individuals, those unable to maintain a stable diet, or those recently treated with pegvaliase are unlikely to be eligible or to benefit from this study.

Why it matters

Potential benefit: If successful, JNT-517 could lower blood phenylalanine levels and offer an additional oral treatment option that may reduce dietary burden and improve symptoms for adults with PKU.

How similar studies have performed: Other approved PKU therapies such as sapropterin and pegvaliase have shown benefit in subsets of patients, but oral small-molecule treatments like JNT-517 are a more novel approach with limited late‑stage data to date.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Males and females ≥18 years of age on Day 1
2. Clinical diagnosis of PKU
3. Average of at least 3 plasma Phe levels (after \>4-hour fast) during Screening period of ≥360 μmol/L
4. Not on pegvaliase within 4 weeks prior to Screening
5. If on sapropterin or large neutral amino acids, such as PheBloc®, NeoPhe®, and PreKunil® at Screening, must be on a stable dose 4 weeks prior to Screening and for the entire study duration.
6. Willing and able to maintain a stable diet in Phe and total protein (intact protein and medical food protein) and able to adjust diet through the duration of the study according to the Dietary Management Guidelines
7. Body weight \>40 kilograms (kg)
8. If biologically 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 highly effective contraceptive methods from Screening until at least 30 days after the last study drug administration
   3. If taking estrogen- or progesterone-based oral contraceptives, must agree to use 2 other highly effective methods of contraception or must agree to sexual abstinence during the study
   4. Must refrain from donating ova during the course of the study and for 30 days after the last dose of the study drug.
9. If a biologically 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 biologically male, must practice sexual abstinence, or if involved in any sexual intercourse that could lead to pregnancy, must agree to use highly effective contraceptive methods 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 biological 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. Participants with psychiatric illness must be well-controlled for the last 6 months prior to the Screening visit and if on medication, on stable medications for the last 3 months.
12. Capable of giving signed informed consent or parent/legal guardian to provide informed consent and the participant to give assent and confirm able to comply with study procedures

Exclusion Criteria:

* Exclusion Criteria

Participants will be excluded from the study if any of the following criteria are met:

1. Any acute or uncontrolled 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
2. Positive for hepatitis B or C or human immunodeficiency virus
3. Any history of malignancy of any organ system (other than non-melanoma skin cancer or in situ cervical cancer), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases
4. Any history of significant liver disease
5. Any history of cataracts or more than minimal cataracts observed during the Screening ophthalmologic examination. Minimal cataracts are defined as changes similar to lens opacities classification system III (LOCS III), lens grade C1, N1 or P1
6. Any surgical or medical conditions that may affect study drug absorption, distribution, metabolism, or excretion
7. Estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73 m2 by 2021 Chronic Kidney Disease Epidemiology Collaboration formula
8. Participation in another investigational drug trial within 30 days or, if known, 5 half-lives of the investigational drug (whichever is longer). For gene therapy or editing trials, participants must have received the intervention \>6 months prior to Screening visit and with stable plasma Phe in the past 2 months prior to Screening visit.
9. Alcohol consumption within 5 days of randomization and/or unwilling to limit to 1 alcoholic drink per day until after the 6-month study visit
10. History of drug/alcohol abuse in the last year
11. Use of any medications that are inhibitors or inducers of cytochrome P450 (CYP3A4) or inhibitors of the transporter P-glycoprotein (P-gp) within 4 weeks prior to randomization and unwilling and/or unable to avoid these medications throughout the treatment duration
12. Use of any medications that are substrates of breast cancer resistance protein (BCRP), multidrug and toxin extrusion (MATE)1, or MATE2-K within 4 weeks prior to randomization and unwilling and/or unable to avoid these medications throughout the treatment duration NOTE: Participants 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.
13. Current, recent, or suspected active viral or bacterial infection within 2 weeks prior to and during the Screening Period
14. Unable to tolerate oral medication or have a condition that would interfere with the absorption of JNT-517
15. Allergy to JNT-517 or any component of the investigational product
16. Any of the following laboratory values at the Screening visit: -Alanine aminotransferase or aspartate aminotransferase values \>1.5× the upper limit of normal (ULN)-Total bilirubin ˃ULN unless history of Gilbert Syndrome and then total bilirubin \>4 milligrams per deciliter (mg/dL) is exclusionary-Hemoglobin \<11.0 grams per deciliter (g/dL) \[\<110.0 grams per liter (g/L)\]-White blood cell count \>ULN-Platelets \<150 × 10\^9/Liter (L) (\<150,000/cubic millimeters \[mm\^3\]).

Where this trial is running

Los Angeles, California and 24 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 PhenylketonuriaPKU
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.