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

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified March 2026 by Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
Information Provided by (Responsible Party)
Otsuka Pharmaceutical Development & Commercialization, Inc.
Clinicaltrials.gov Identifier
NCT06971731
Other Study ID Numbers:
JNT517-301
First Submitted
May 6, 2025
First Posted
May 13, 2025
Last Update Posted
May 3, 2026
Last Verified
March 2026

ClinicalTrials.gov processed this data on April 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study Description

Condition or DiseaseIntervention/Treatment
Phenylketonuria
Drug: JNT-517 TabletDrug: JNT-517 TabletDrug: Placebo Tablet: BID

Study Design

Study TypeInterventional
Actual Enrollment120 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleA Phase 3, Double-Blind, Randomized, Two-Period, Multicenter, Placebo-Controlled, Efficacy and Safety Study of JNT-517 for the Treatment of Participants With Phenylketonuria
Study Start DateOctober 19, 2025
Actual Primary Completion Date1yr 8mos from now
Actual Study Completion Date1yr 9mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
Drug: JNT-517 - 150 mg BID (Tablet)
Drug: JNT-517 Tablet
JNT-517: 75 mg BID
Drug: JNT-517 - 75 mg BID (Tablet)
Drug: JNT-517 Tablet
JNT-517: 75 mg BID
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

Outcome Measures

Primary Outcome Measures
  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
Secondary Outcome Measures
  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
  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
  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
  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
  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
  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.
  7. Change From Baseline in Dietary Phe Intake While Achieving Plasma Phe <360 µmol/L
  8. Number of Participants With Treatment-Emergent Adverse Events and Serious Treatment-Emergent Adverse Events
  9. Percentage of Participants With ≥30% and ≥50% Reduction From Baseline in Plasma Phe at 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
  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
  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
  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
  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
  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
  16. Absolute Change From Baseline in Plasma Phe in the JNT-517 75 mg BID and 150 mg BID Dose Groups During Period 2
  17. Percent Change From Baseline in Plasma Phe in the JNT-517 75 mg BID and 150 mg BID Dose Groups During Period 2
  18. Percentage of Participants With ≥30% and ≥50% Reduction From Baseline in Plasma Phe During Period 2
  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.
  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.
  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.
  22. Change From Baseline in Dietary Protein Intake While Maintaining Plasma Phe <360 µmol/L
  23. Percentage of Participants Achieving Recommended Dietary Allowance (RDA) for Natural Intact Protein Intake While Maintaining Plasma Phenylalanine <360 µmol/L
  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

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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 \[mm\^3\]).

Contacts and Locations

Sponsors and CollaboratorsOtsuka Pharmaceutical Development & Commercialization, Inc.
Locations
University of California Los Angeles (UCLA) School of Medicine | Los Angeles California, United States, 90024University of Florida (UF) Health Shands Hospital | Gainesville Florida, United States, 32608University of South Florida | Tampa Florida, United States, 33606Ann & Robert H. Lurie Children's Hospital of Chicago | Chicago Illinois, United States, 60611Oregon Health and Science University | Portland Oregon, United States, 97239University of Pittsburgh Medical Center (UPMC) - Children's Hospital of Pittsburgh | Pittsburgh Pennsylvania, United States, 15201Vanderbilt University Medical Center | Nashville Tennessee, United States, 37232University of Texas Southwestern | Dallas Texas, United States, 75390University of Texas Health (UTHealth) Science Center at Houston | Houston Texas, United States, 77030-1501Utah Health - The University of Utah Hospital | Salt Lake City Utah, United States, 84112Royal Adelaide Hospital | Adelaide , Australia, 5000Royal Melbourne Hospital | Parkville , Australia, Mater Health - Mater Hospital Brisbane | South Brisbane , Australia, 4104M.A.G.I.C Clinic | Calgary Alberta, Canada, T2E 7H7Fakultní nemocnice Královské Vinohrady | Prague , Czechia, Centre Hospitalier Régional Universitaire (CHRU) de Tours - Hôpital Bretonneau | Tours , France, Universitätsklinikum Münster | Münster , Germany, Nihon University Hospital | Chiyoda-ku , Japan, Fujita Health University | Kutsukake-cho , Japan, Osaka Metropolitan University Hospital | Osaka , Japan, Universitair Medisch Centra (AMC)- Amsterdam | Amsterdam , Netherlands, Beatrix Children's Hospital | Groningen , Netherlands, Pomorski Uniwersytet Medyczny w Szczecinie | Szczecin , Poland, Hospital Universitario Ramón y Cajal | Madrid , Spain, Hospital Clinico Universitario de Santiago de Compostela | Santiago de Compostela , Spain,