First-in-Human, Multiple Part Clinical Study of JNT-517 in Healthy Participants and in Participants With Phenylketonuria

A Phase 1/2, First-In-Human, Multiple Part, Single Ascending and Multiple Dose Study of JNT-517 in Healthy Participants and in Participants With Phenylketonuria

The goal of Parts A and B of this Phase 1/2, first-in-human, randomized study is to assess the safety, tolerability, and pharmacokinetics (PK) of single (SAD) and multiple (MAD) ascending doses of oral JNT-517 in healthy participants. In Part C, the goal is to evaluate the differences in bioavailability between a tablet and suspension formulation of JNT-517 and the food effect in healthy volunteers. All participants in Part C will receive JNT-517. The goal of Part D is to assess the safety, tolerability, PK, and effect on urinary Phe and other amino acids of JNT-517 in participants with phenylketonuria (PKU). Participants in Part D will receive either JNT-517 or placebo and will be blinded to their treatment assignment.

The study consists of 6 parts:

• Part A: SAD in healthy participants -randomized, double-blind, placebo-controlled
• Part B: MAD in healthy participants (14 days)-randomized, double-blind, placebo-controlled
• Part C: Relative bioavailability of 2 formulations and food effect in healthy participants-randomized, open-label
• Part D: Phase 2 in participants with PKU (4 weeks)-randomized, double-blind, placebo-controlled
• Part E: Phase 2 in participants with PKU (4 weeks) open label
• Part F: SAD Phase 1 in healthy participants, randomized, double-blind, placebo-controlled

In each part, participants will complete a Screening Period, a Treatment Period, and a Follow-up Period for safety.

Study Overview

• Status: Completed
• Conditions: Phenylketonuria
• Intervention / Treatment: Drug: JNT-517 Suspension; Drug: Placebo Suspension; Drug: JNT-517 Tablet; Drug: Placebo Tablet

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Australia
  • Melbourne VIC
    • Melbourne, Melbourne VIC, Australia, 3004
      • Nucleus Network Melbourne
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Mater Misericordia Ltd
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida College of Medicine
    • Tampa, Florida, United States, 33620
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Rare Disease Research
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Sciences University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Utah Health - The University of Utah Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Key Inclusion Criteria:

Parts A, B, C, and F:

1. Males and females 18 to 55 years of age.
2. Medically healthy with no clinically significant medical history.
3. Body mass index (BMI) of 18-40 kg/m2 and total body weight >50 kg (110 lbs).

4. Non-smoker for at least 2 weeks prior to dosing and willing to abstain during the study.

   Part D and E:

5. Males and females 18 to 65 years of age, inclusive.
6. Diagnosis of PKU with a confirmed genotype.
7. At least 2 plasma Phe levels >600 μM over the past 12 months.

8. BMI of 18-40 kg/m2.

   All Parts:

9. Females of childbearing potential must agree to use 2 highly effective contraceptive methods.
10. Capable of giving signed informed consent and able to comply with study procedures.

Key Exclusion Criteria:

All Parts:

1. Any acute or 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 in the last 5 years, excluding non-melanoma skin cancer.
4. Any history of liver disease.
5. Any surgical or medical conditions that may affect study drug absorption, distribution, metabolism, or excretion.
6. Participation in another investigational drug trial within 30 days or, if known, 5 half-lives of the investigational drug (whichever is longer).
7. History of drug/alcohol abuse in the last year.
8. Current, recent, or suspected infection within 4 weeks of Screening of SARS-CoV-2/COVID-19.
9. Received a vaccine for SARS-CoV-2/COVID-19 within 14 days of Screening.
10. Unable to tolerate oral medication.
11. Allergy to JNT-517 or any component of the investigational product.
12. Received >50 mL of blood or plasma within 30 days of Screening or >500 mL of blood or plasma within 60 days of Screening.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JNT-517 MAD (Part B); JNT-517 or placebo once or twice daily for 14 days, with first daily dose given after an overnight fast.	Drug: JNT-517 Suspension; JNT-517 in on-site compounded suspension; Drug: Placebo Suspension; On-site compounded placebo suspension
Experimental: JNT-517 Suspension Then Tablet Fasted Then Tablet Fed (Part C); Single dose of JNT-517 suspension, JNT-517 tablet in a fasted state, and JNT-517 tablet in a fed state in a sequential, open-label manner. Each treatment is separated by a minimum of 5 half-lives.	Drug: JNT-517 Suspension; JNT-517 in on-site compounded suspension; Drug: JNT-517 Tablet; JNT-517 tablets, 25 mg and 75 mg
Experimental: JNT-517 Tablet Fasted Then Tablet Fed Then Suspension (Part C); Single dose of JNT-517 tablet in a fasted state, JNT-517 tablet in a fed state, and JNT-517 suspension in a sequential, open-label manner. Each treatment is separated by a minimum of 5 half-lives.	Drug: JNT-517 Suspension; JNT-517 in on-site compounded suspension; Drug: JNT-517 Tablet; JNT-517 tablets, 25 mg and 75 mg
Experimental: JNT-517 Tablet Fed Then Suspension Then Tablet Fasted (Part C); Single dose of JNT-517 tablet in a fed state, JNT-517 suspension, and JNT-517 tablet in a fasted state in a sequential, open-label manner. Each treatment is separated by a minimum of 5 half-lives.	Drug: JNT-517 Suspension; JNT-517 in on-site compounded suspension; Drug: JNT-517 Tablet; JNT-517 tablets, 25 mg and 75 mg
Experimental: JNT-517 SAD (Part A and Part F); Single dose of JNT-517 or placebo in fasted state.	Drug: JNT-517 Suspension; JNT-517 in on-site compounded suspension; Drug: Placebo Suspension; On-site compounded placebo suspension
Experimental: JNT-517 PKU (Part D and E); JNT-517 or placebo daily for 4 weeks. Dose is based on data from Parts A, B, and C.	Drug: JNT-517 Tablet; JNT-517 tablets, 25 mg and 75 mg; Drug: Placebo Tablet; Matching film-coated placebo tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with treatment-emergent adverse events	Reported based on results of 12-lead ECGs, vital signs, clinical laboratory tests, and other medical assessments.	Parts A/C/F: Screening to Day 8; Part B: Screening to Day 21; Part D/E: Screening to Day 35

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparison of Tmax of JNT-517 in fed and fasted states	Part C only	Pre-dose to 72 hrs post-dose on Day 1
Comparison of Cmax of JNT-517 in fed and fasted states	Part C only	Pre-dose to 72 hrs post-dose on Day 1
Comparison of AUC of JNT-517 in fed and fasted states	Part C only	Pre-dose to 72 hrs post-dose on Day 1
Plasma area under the concentration-time curve (AUC) of JNT-517		Parts A/C/F: pre-dose to 72 hrs post-dose on Day 1; Part B: pre-dose to 24 hrs post-dose on Days 1, 14 and pre-dose on Days 3, 13; Part D/E: pre-dose to 4 hrs post-dose on Days 1, 14, 28
Maximum observed plasma concentration (Cmax) of JNT-517		Parts A/C/F: pre-dose to 72 hrs post-dose on Day 1; Part B: pre-dose to 24 hrs post-dose on Days 1, 14 and pre-dose on Days 3, 13; Part D/E: pre-dose to 4 hrs post-dose on Days 1, 14, 28
Time to maximum plasma concentration (Tmax) of JNT-517		Parts A/C/F: pre-dose to 72 hrs post-dose on Day 1; Part B: pre-dose to 24 hrs post-dose on Days 1, 14 and pre-dose on Days 3, 13; Part D/E: pre-dose to 4 hrs post-dose on Days 1, 14, 28
Plasma terminal half-life (t1/2) of JNT-517		Parts A/C/F: pre-dose to 72 hrs post-dose on Day 1; Part B: pre-dose to 24 hrs post-dose on Days 1, 14 and pre-dose on Days 3, 13; Part D/E: pre-dose to 4 hrs post-dose on Days 1, 14, 28
Changes in urinary amino acid levels	Part D/E only. Urine samples will be collected at the indicated timepoints and analyzed for amino acid levels, including Phe.	Screening and Days 1, 7, 14, 21, 28

Collaborators and Investigators

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2022
• Primary Completion (Actual): July 14, 2025
• Study Completion (Actual): July 14, 2025

Study Registration Dates

• First Submitted: February 11, 2023
• First Submitted That Met QC Criteria: March 10, 2023
• First Posted (Actual): March 23, 2023

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: PKU
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Amino Acid Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Phenylketonurias
• Other Study ID Numbers: JNT517-101

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; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No