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

NCT06971731 | Recruiting Phase 3 FDA Drug

• 1 other identifier: JNT517-301
• Study Type: interventional
• Target: 120
• Locations: 10 countries
• Sites: 25

Brief 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

Conditions

Phenylketonuria

Keywords

Phenylketonuria; PKU

Outcome Measures

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

  Baseline to End of Period 1 (Week 6)

Secondary Outcomes (24)

• 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

  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

  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

  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

  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

  Baseline to End of Period 1 (Week 6)

Study Arms (3)

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

EXPERIMENTAL

Drug: JNT-517 Tablet

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

EXPERIMENTAL

Drug: JNT-517 Tablet

Placebo - BID

PLACEBO COMPARATOR

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

JNT-517 Tablet DRUG

JNT-517: 75 mg BID

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

Placebo Tablet: BID DRUG

Placebo Tablet: BID

Placebo - BID

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females ≥18 years of age on Day 1
• Clinical diagnosis of PKU
• Average of at least 3 plasma Phe levels (after \>4-hour fast) during Screening period of ≥360 μmol/L
• Not on pegvaliase within 4 weeks prior to Screening
• 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.
• 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
• Body weight \>40 kilograms (kg)
• If biologically female of childbearing potential:
• Must have a negative serum pregnancy test at Screening and a negative urine pregnancy test by Day 1
• 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
• 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
• Must refrain from donating ova during the course of the study and for 30 days after the last dose of the study drug.
• If a biologically female not of childbearing potential or postmenopausal, defined as follows:
• Has had surgical sterilization (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy)
• Has had amenorrhea for minimum of 1 year with confirmation by levels of follicle stimulating hormone testing

You may not qualify if:

• Participants will be excluded from the study if any of the following criteria are met:
• 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
• Positive for hepatitis B or C or human immunodeficiency virus
• 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
• Any history of significant liver disease
• 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
• Any surgical or medical conditions that may affect study drug absorption, distribution, metabolism, or excretion
• Estimated glomerular filtration rate (eGFR) \<60 mL/min/1.73 m2 by 2021 Chronic Kidney Disease Epidemiology Collaboration formula
• 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.
• 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
• History of drug/alcohol abuse in the last year
• 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
• 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.
• Current, recent, or suspected active viral or bacterial infection within 2 weeks prior to and during the Screening Period
• Unable to tolerate oral medication or have a condition that would interfere with the absorption of JNT-517

Sponsors & Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.: lead

Study Sites (25)

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

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

Related Links

• Otsuka Clinical Trial Website
• Otsuka Clinical Trial Transparency

MeSH Terms

Conditions

Phenylketonurias

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Amino Acid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Otsuka Call Center

CONTACT

844-687-8522; otsuka-professionalservices@otsuka-us.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2025
• First Posted: May 14, 2025
• Study Start: October 20, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): April 1, 2028
• Last Updated: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• 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.
• Access Criteria: Otsuka will share data on the Vivli data sharing platform which can be found here: https://vivli.org/ourmember/Otsuka/

Locations

DE (1); CZ (1); CA (1); US (10); ES (2); AU (3); FR (1); JP (3); PL (1); NL (2)