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
1 other identifier
interventional
111
2 countries
15
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Oct 2022
Typical duration for phase_1
15 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
October 31, 2022
CompletedFirst Submitted
Initial submission to the registry
February 11, 2023
CompletedFirst Posted
Study publicly available on registry
March 23, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 14, 2025
CompletedStudy Completion
Last participant's last visit for all outcomes
July 14, 2025
CompletedMay 6, 2026
May 1, 2026
2.7 years
February 11, 2023
May 1, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 Outcomes (8)
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
Comparison of Tmax of JNT-517 in fed and fasted states
Pre-dose to 72 hrs post-dose on Day 1
- +3 more secondary outcomes
Study Arms (6)
JNT-517 SAD (Part A and Part F)
EXPERIMENTALSingle dose of JNT-517 or placebo in fasted state.
JNT-517 MAD (Part B)
EXPERIMENTALJNT-517 or placebo once or twice daily for 14 days, with first daily dose given after an overnight fast.
JNT-517 Suspension Then Tablet Fasted Then Tablet Fed (Part C)
EXPERIMENTALSingle 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.
JNT-517 Tablet Fasted Then Tablet Fed Then Suspension (Part C)
EXPERIMENTALSingle 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.
JNT-517 Tablet Fed Then Suspension Then Tablet Fasted (Part C)
EXPERIMENTALSingle 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.
JNT-517 PKU (Part D and E)
EXPERIMENTALJNT-517 or placebo daily for 4 weeks. Dose is based on data from Parts A, B, and C.
Interventions
JNT-517 in on-site compounded suspension
On-site compounded placebo suspension
JNT-517 tablets, 25 mg and 75 mg
Eligibility Criteria
You may qualify if:
- Parts A, B, C, and F:
- Males and females 18 to 55 years of age.
- Medically healthy with no clinically significant medical history.
- Body mass index (BMI) of 18-40 kg/m2 and total body weight \>50 kg (110 lbs).
- Non-smoker for at least 2 weeks prior to dosing and willing to abstain during the study.
- Part D and E:
- Males and females 18 to 65 years of age, inclusive.
- Diagnosis of PKU with a confirmed genotype.
- At least 2 plasma Phe levels \>600 μM over the past 12 months.
- BMI of 18-40 kg/m2.
- All Parts:
- Females of childbearing potential must agree to use 2 highly effective contraceptive methods.
- Capable of giving signed informed consent and able to comply with study procedures.
You may not qualify if:
- All Parts:
- 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.
- Positive for hepatitis B or C or human immunodeficiency virus.
- Any history of malignancy in the last 5 years, excluding non-melanoma skin cancer.
- Any history of liver disease.
- Any surgical or medical conditions that may affect study drug absorption, distribution, metabolism, or excretion.
- Participation in another investigational drug trial within 30 days or, if known, 5 half-lives of the investigational drug (whichever is longer).
- History of drug/alcohol abuse in the last year.
- Current, recent, or suspected infection within 4 weeks of Screening of SARS-CoV-2/COVID-19.
- Received a vaccine for SARS-CoV-2/COVID-19 within 14 days of Screening.
- Unable to tolerate oral medication.
- Allergy to JNT-517 or any component of the investigational product.
- Received \>50 mL of blood or plasma within 30 days of Screening or \>500 mL of blood or plasma within 60 days of Screening.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (15)
University of Florida College of Medicine
Gainesville, Florida, 32610, United States
University of South Florida
Tampa, Florida, 33620, United States
Rare Disease Research
Atlanta, Georgia, 30329, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611, United States
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
Oregon Health & Sciences University
Portland, Oregon, 97239, United States
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224, United States
UT Southwestern Medical Center
Dallas, Texas, 75390, United States
University of Texas Health Science Center at Houston
Houston, Texas, 77030, United States
Utah Health - The University of Utah Hospital
Salt Lake City, Utah, 84112, United States
Nucleus Network Melbourne
Melbourne, Melbourne VIC, 3004, Australia
Westmead Hospital
Westmead, New South Wales, 2145, Australia
Mater Misericordia Ltd
South Brisbane, Queensland, 4101, Australia
Royal Adelaide Hospital
Adelaide, South Australia, 5000, Australia
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Masking Details
- Parts A, B, D, and F are blinded. Parts C and E are open-label.
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 11, 2023
First Posted
March 23, 2023
Study Start
October 31, 2022
Primary Completion
July 14, 2025
Study Completion
July 14, 2025
Last Updated
May 6, 2026
Record last verified: 2026-05
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- 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/
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.