A Study of JNT-517 in Participants With Phenylketonuria (PKU)

April 28, 2026 updated by: Otsuka Pharmaceutical Development & Commercialization, Inc.

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

The goal of this Phase 3, randomized study is to assess the safety, efficacy, tolerability, and pharmacokinetics (PK) of oral JNT-517 in adults (18 years of age or older) with PKU. Participants will receive either JNT-517 or placebo and will be blinded to their treatment assignment. Participants will have a 2 in 3 (or approximately 67%) chance of receiving JNT-517 during the first part of the study which will last approximately six weeks. During the second part of the study every participant who continues in the study will receive one of two doses of JNT-517 for an additional 46 weeks. The study requires a screening period of up to 35 days to ensure dietary stabilization and amino acid levels required to meet study eligibility. In total, participation in the study could last for up to 400 days.

Participants will:

Take 75 mg JNT-517 or 150 mg JNT-517, or a placebo BID (2x per day) for approximately 365 days; Visit the clinic or have a mobile health nurse visit your home for checkups and tests; Collect urine sample at home and bring to clinic on specified days; Keep a food diary 3 days before each study visit

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
      • Adelaide, Australia, 5000
      • Parkville, Australia
      • South Brisbane, Australia, 4104
  • Canada
    • Alberta
  • Czechia
      • Prague, Czechia
  • France
      • Tours, France
        • Recruiting
        • Centre Hospitalier Régional Universitaire (CHRU) de Tours - Hôpital Bretonneau
        • Contact:
        • Principal Investigator:
          • Francois Maillot
  • Germany
  • Japan
  • Netherlands
      • Amsterdam, Netherlands
      • Groningen, Netherlands
  • Poland
      • Szczecin, Poland
  • Spain
      • Madrid, Spain
      • Santiago de Compostela, Spain
        • Recruiting
        • Hospital Clínico Universitario de Santiago de Compostela
        • Contact:
        • Principal Investigator:
          • Alvaro Hermida
  • United States
    • California
      • Los Angeles, California, United States, 90024
        • Recruiting
        • University of California Los Angeles (UCLA) School of Medicine
        • Contact:
        • Principal Investigator:
          • Nicola Longo
    • Florida
      • Gainesville, Florida, United States, 32608
      • Tampa, Florida, United States, 33606
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Ann & Robert H. Lurie Children's Hospital of Chicago
        • Contact:
        • Principal Investigator:
          • Erika Vucko
    • Oregon
      • Portland, Oregon, United States, 97239
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15201
        • Recruiting
        • University of Pittsburgh Medical Center (UPMC) - Children's Hospital of Pittsburgh
        • Principal Investigator:
          • Gerard Vockley
        • Contact:
    • Tennessee
      • Nashville, Tennessee, United States, 37232
    • Texas
      • Dallas, Texas, United States, 75390
      • Houston, Texas, United States, 77030-1501
        • Recruiting
        • University of Texas Health (UTHealth) Science Center at Houston
        • Principal Investigator:
          • Hope Northrup
        • Contact:
    • Utah
      • Salt Lake City, Utah, United States, 84112

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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]).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Drug: JNT-517 - 150 mg BID (Tablet)
Drug: JNT-517 Tablet
JNT-517: 75 mg BID
Drug: JNT-517 Tablet
JNT-517: 150 mg BID
Experimental: Drug: JNT-517 - 75 mg BID (Tablet)
Drug: JNT-517 Tablet
JNT-517: 75 mg BID
Drug: JNT-517 Tablet
JNT-517: 150 mg BID
Placebo Comparator: Placebo - BID
One-third (1/3) of participants in the study will be assigned to placebo twice daily (BID) during Treatment Period Part 1. After 6 weeks, these participants will transition to Treatment Period Part 2 and receive JNT-517 at 150 mg BID for 46 weeks.
Drug: Placebo Tablet: BID
Placebo Tablet: BID

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Absolute Change in Plasma Phenylalanine (Phe) From Baseline to the Mean of Weeks 2, 4, and 6 in the JNT-517 150 mg BID Dose Group at End of Period 1
Time Frame: Baseline to End of Period 1 (Week 6)
Baseline to End of Period 1 (Week 6)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change in Plasma Phe From Baseline to the Mean of Weeks 2, 4, and 6 in the JNT-517 150 mg BID Dose Group at End of Period 1
Time Frame: Baseline to End of Period 1 (Week 6)
Baseline to End of Period 1 (Week 6)
Percentage of Participants Achieving Plasma Phe <600 Micromoles per Liter (µmol/L) at End of Period 1 Among Participants With Baseline ≥600 µmol/L in the 150 mg BID and 75 mg BID Groups
Time Frame: Baseline to End of Period 1 (Week 6)
Baseline to End of Period 1 (Week 6)
Percentage of Participants Achieving Plasma Phe <360 µmol/L at End of Period 1 in the 150 mg BID and 75 mg BID Groups
Time Frame: Baseline to End of Period 1 (Week 6)
Baseline to End of Period 1 (Week 6)
Absolute Change in Plasma Phe From Baseline to the Mean of Weeks 2, 4, and 6 in the JNT-517 75 mg BID Group at End of Period 1
Time Frame: Baseline to End of Period 1 (Week 6)
Baseline to End of Period 1 (Week 6)
Percent Change in Plasma Phe From Baseline to the Mean of Weeks 2, 4, and 6 in the JNT-517 75 mg BID Group at End of Period 1
Time Frame: Baseline to End of Period 1 (Week 6)
Baseline to End of Period 1 (Week 6)
Change From Baseline in ADHD Rating Scale-5 (ADHD-RS-5) Inattentive Subscore in Participants With Baseline Inattentive Subscore >9 in the JNT-517 150 mg BID and 75 mg BID dose Groups at End of Period 1
Time Frame: Baseline to End of Period 1 (Week 6)
The ADHD Rating Scale-5 (ADHD-RS-5) Inattentive Subscore (sum of 9 inattentive items) ranges from 0 to 27, with higher scores indicating greater severity of inattentive symptoms. A decrease in the subscore represents an improvement in symptoms.
Baseline to End of Period 1 (Week 6)
Change From Baseline in Dietary Phe Intake While Achieving Plasma Phe <360 µmol/L
Time Frame: Baseline to End of Period 1 (Week 6)
Baseline to End of Period 1 (Week 6)
Number of Participants With Treatment-Emergent Adverse Events and Serious Treatment-Emergent Adverse Events
Time Frame: From first dose of the study drug through Week 56
From first dose of the study drug through Week 56
Percentage of Participants With ≥30% and ≥50% Reduction From Baseline in Plasma Phe at Week 6
Time Frame: Baseline to End of Period 1 (Week 6)
Baseline to End of Period 1 (Week 6)
Percentage of Participants Achieving Plasma Phe <120 µmol/L at End of Period 1 in the 150 mg BID and 75 mg BID Groups
Time Frame: End of Period 1 (Week 6)
End of Period 1 (Week 6)
Absolute Change in Plasma Phe From Baseline to Weeks 2, 4, and 6 of Period 1 in the JNT-517 150 mg BID and 75 mg BID Groups
Time Frame: Baseline to End of Period 1 (Week 6)
Baseline to End of Period 1 (Week 6)
Percent Change in Plasma Phe From Baseline to Weeks 2, 4, and 6 of Period 1 in the JNT-517 150 mg BID and 75 mg BID Groups
Time Frame: Baseline to End of Period 1 (Week 6)
Baseline to End of Period 1 (Week 6)
Percentage of Participants Achieving Plasma Phe <600 µmol/L Among Participants With Baseline ≥600 µmol/L in the JNT-517 150 mg BID and 75 mg BID Dose Groups at the End of Period 2
Time Frame: Baseline to End of Period 2 (Week 52)
Baseline to End of Period 2 (Week 52)
Percentage of Participants Achieving Plasma Phe <360 µmol/L in the JNT-517 150 mg BID and 75 mg BID Dose Groups at the End of Period 2
Time Frame: End of Period 2 (Week 52)
End of Period 2 (Week 52)
Percentage of Participants Achieving Plasma Phe <120 µmol/L in the JNT-517 150 mg BID and 75 mg BID Dose Groups at the End of Period 2
Time Frame: End of Period 2 (Week 52)
End of Period 2 (Week 52)
Absolute Change From Baseline in Plasma Phe in the JNT-517 75 mg BID and 150 mg BID Dose Groups During Period 2
Time Frame: Baseline to End of Period 2 (Week 52)
Baseline to End of Period 2 (Week 52)
Percent Change From Baseline in Plasma Phe in the JNT-517 75 mg BID and 150 mg BID Dose Groups During Period 2
Time Frame: Baseline to End of Period 2 (Week 52)
Baseline to End of Period 2 (Week 52)
Percentage of Participants With ≥30% and ≥50% Reduction From Baseline in Plasma Phe During Period 2
Time Frame: Baseline to End of Period 2 (Week 52)
Baseline to End of Period 2 (Week 52)
Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Stop Signal Reaction Time at End of Period 1
Time Frame: Baseline to End of Period 1 (Week 6)
The CANTAB Stop Signal Task measures response inhibition. Stop Signal Reaction Time (SSRT) reflects the time required to inhibit a response, with longer times indicating poorer inhibitory control. A decrease from baseline indicates improvement.
Baseline to End of Period 1 (Week 6)
Change From Baseline in CANTAB Stop Signal Reaction Time During Period 2
Time Frame: Baseline to End of Period 2 (Week 52)
The CANTAB Stop Signal Task measures response inhibition. SSRT reflects the time required to inhibit a response, with longer times indicating poorer inhibitory control. A decrease from baseline indicates improvement.
Baseline to End of Period 2 (Week 52)
Change From Baseline in ADHD Rating Scale-5 (ADHD-RS-5) Inattentive Subscore in Participants with Baseline Inattentive Subscore >9 in the JNT-517 150 mg BID and 75 mg BID Dose Groups During Period 2
Time Frame: Baseline to End of Period 2 (Week 52)
The ADHD Rating Scale-5 (ADHD-RS-5) Inattentive Subscore (sum of 9 inattentive items) ranges from 0 to 27, with higher scores indicating greater severity of inattentive symptoms. A decrease in the subscore represents an improvement in symptoms.
Baseline to End of Period 2 (Week 52)
Change From Baseline in Dietary Protein Intake While Maintaining Plasma Phe <360 µmol/L
Time Frame: Baseline to End of Period 2 (Week 52)
Baseline to End of Period 2 (Week 52)
Percentage of Participants Achieving Recommended Dietary Allowance (RDA) for Natural Intact Protein Intake While Maintaining Plasma Phenylalanine <360 µmol/L
Time Frame: End of Period 2 (Week 52)
End of Period 2 (Week 52)
Percentage of Participants Achieving Two Times the RDA for Natural Intact Protein Intake Consistent With an Unrestricted Diet While Maintaining Plasma Phenylalanine <360 µmol/L
Time Frame: End of Period 2 (Week 52)
End of Period 2 (Week 52)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc.

Collaborators

Otsuka Pharmaceutical Development & Commercialization, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 20, 2025

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

April 1, 2028

Study Registration Dates

First Submitted

May 7, 2025

First Submitted That Met QC Criteria

May 7, 2025

First Posted (Actual)

May 14, 2025

Study Record Updates

Last Update Posted (Actual)

May 4, 2026

Last Update Submitted That Met QC Criteria

April 28, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JNT517-301

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.

IPD Sharing Time Frame

Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.

IPD Sharing Access Criteria

Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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