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RecruitingNCT06971731Updated Jul 8, 2026

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

A Phase 3 interventional study of JNT-517 Tablet and JNT-517 Tablet in Phenylketonuria, sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc.. Recruiting at 26 sites in 10 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-07-08.

Sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc. · Phase 3, Interventional, and Treatment

From the registry’s dates

  • Started Oct 2025; still recruiting 11 months later.
Phase
Phase 3
Study type
Interventional
Enrollment
120
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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

02

Conditions studied

  • Phenylketonuria

Browse trials for

Keywords

  • Phenylketonuria
  • PKU
03

In context

Phenylketonurias

183 studies on the registry are indexed under Phenylketonurias; 38 are open to participants now.

This study's planned enrollment of 120 is above the median of 25 across 114 interventional studies indexed under Phenylketonurias.

Browse Phenylketonurias studies →

Lead sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc. is the lead sponsor of 289 studies on the registry; 18 are open to participants now.

Of its 104 completed or terminated interventional studies of FDA-regulated products, 69 (66%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility 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]).
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
120 participants (estimated)

Study arms

  • Experimental
    Drug: JNT-517 - 150 mg BID (Tablet)

    Drug: JNT-517 Tablet

  • Experimental
    Drug: JNT-517 - 75 mg BID (Tablet)

    Drug: JNT-517 Tablet

  • 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

Interventions

  • DrugJNT-517 Tablet

    JNT-517: 75 mg BID

  • DrugJNT-517 Tablet

    JNT-517: 150 mg BID

  • DrugPlacebo Tablet: BID

    Placebo Tablet: BID

06

What researchers measure

Primary outcomes

  1. 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)

Secondary outcomes

  1. 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)

  2. 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)

  3. 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)

  4. 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)

  5. 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)

  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

    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.

    Time frame: Baseline to End of Period 1 (Week 6)

  7. Change From Baseline in Dietary Phe Intake While Achieving Plasma Phe <360 µmol/L

    Time frame: Baseline to End of Period 1 (Week 6)

  8. 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

  9. 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)

  10. 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)

  11. 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)

  12. 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)

  13. 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)

  14. 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)

  15. 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)

  16. 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)

  17. 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)

  18. 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)

  19. Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Stop Signal Reaction Time at End of Period 1

    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.

    Time frame: Baseline to End of Period 1 (Week 6)

  20. Change From Baseline in CANTAB Stop Signal Reaction Time During Period 2

    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.

    Time frame: Baseline to End of Period 2 (Week 52)

  21. 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

    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.

    Time frame: Baseline to End of Period 2 (Week 52)

  22. Change From Baseline in Dietary Protein Intake While Maintaining Plasma Phe <360 µmol/L

    Time frame: Baseline to End of Period 2 (Week 52)

  23. 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)

  24. 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)

07

Study locations

26 of 26 sites recruiting
  • University of California Los Angeles (UCLA) School of Medicine
    Los Angeles, California 90024, United States
    Recruiting
  • University of Florida (UF) Health Shands Hospital
    Gainesville, Florida 32608, United States
    Recruiting
  • University of South Florida
    Tampa, Florida 33606, United States
    Recruiting
  • Ann & Robert H. Lurie Children's Hospital of Chicago
    Chicago, Illinois 60611, United States
    Recruiting
  • Oregon Health and Science University
    Portland, Oregon 97239, United States
    Recruiting
  • University of Pittsburgh Medical Center (UPMC) - Children's Hospital of Pittsburgh
    Pittsburgh, Pennsylvania 15201, United States
    Recruiting
  • Vanderbilt University Medical Center
    Nashville, Tennessee 37232, United States
    Recruiting
  • University of Texas Southwestern
    Dallas, Texas 75390, United States
    Recruiting
  • University of Texas Health (UTHealth) Science Center at Houston
    Houston, Texas 77030-1501, United States
    Recruiting
  • Utah Health - The University of Utah Hospital
    Salt Lake City, Utah 84112, United States
    Recruiting
  • Royal Adelaide Hospital
    Adelaide, 5000, Australia
    Recruiting
  • Royal Melbourne Hospital
    Parkville, Australia
    Recruiting
  • Mater Health - Mater Hospital Brisbane
    South Brisbane, 4104, Australia
    Recruiting
  • M.A.G.I.C Clinic
    Calgary, Alberta T2E 7H7, Canada
    Recruiting
  • Fakultní nemocnice Královské Vinohrady
    Prague, Czechia
    Recruiting
  • Centre Hospitalier Régional Universitaire (CHRU) de Tours - Hôpital Bretonneau
    Tours, France
    Recruiting
  • Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz
    Mainz, Germany
    Recruiting
  • Universitätsklinikum Münster
    Münster, Germany
    Recruiting
  • Nihon University Hospital
    Chiyoda-ku, Japan
    Recruiting
  • Fujita Health University
    Kutsukake-cho, Japan
    Recruiting
  • Osaka Metropolitan University Hospital
    Osaka, Japan
    Recruiting
  • Universitair Medisch Centra (AMC)- Amsterdam
    Amsterdam, Netherlands
    Recruiting
  • Beatrix Children's Hospital
    Groningen, Netherlands
    Recruiting
  • Pomorski Uniwersytet Medyczny w Szczecinie
    Szczecin, Poland
    Recruiting
  • Hospital Universitario Ramón y Cajal
    Madrid, Spain
    Recruiting
  • Hospital Clinico Universitario de Santiago de Compostela
    Santiago de Compostela, Spain
    Recruiting
08

References and documents

Individual participant data

Plan to share: Yes — 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.

Supporting information: Study protocol, Sap, Icf

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jul 8, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT06971731
Lead sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
Responsible party
Sponsor
First posted
May 14, 2025
Start date
Oct 20, 2025
Primary completion
Mar 1, 2028 (estimated)
Completion
Apr 1, 2028 (estimated)
Last update
Jul 8, 2026

Study contacts

Otsuka Call Center
Contact
otsuka-professionalservices@otsuka-us.com
844-687-8522

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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