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

NCT ID: NCT05781399

Last Updated: 2025-07-31

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 135 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-10-31
• Study Completion Date: 2025-12-15

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.

Conditions

Phenylketonuria

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

JNT-517 SAD (Part A and Part F)

Single dose of JNT-517 or placebo in fasted state.

Group Type: EXPERIMENTAL

JNT-517 Suspension

Intervention Type: DRUG

JNT-517 in on-site compounded suspension

Placebo Suspension

Intervention Type: DRUG

On-site compounded placebo suspension

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.

Group Type: EXPERIMENTAL

JNT-517 Suspension

Intervention Type: DRUG

JNT-517 in on-site compounded suspension

Placebo Suspension

Intervention Type: DRUG

On-site compounded placebo suspension

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.

Group Type: EXPERIMENTAL

JNT-517 Suspension

Intervention Type: DRUG

JNT-517 in on-site compounded suspension

JNT-517 Tablet

Intervention Type: DRUG

JNT-517 tablets, 25 mg and 75 mg

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.

Group Type: EXPERIMENTAL

JNT-517 Suspension

Intervention Type: DRUG

JNT-517 in on-site compounded suspension

JNT-517 Tablet

Intervention Type: DRUG

JNT-517 tablets, 25 mg and 75 mg

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.

Group Type: EXPERIMENTAL

JNT-517 Suspension

Intervention Type: DRUG

JNT-517 in on-site compounded suspension

JNT-517 Tablet

Intervention Type: DRUG

JNT-517 tablets, 25 mg and 75 mg

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.

Group Type: EXPERIMENTAL

JNT-517 Tablet

Intervention Type: DRUG

JNT-517 tablets, 25 mg and 75 mg

Placebo Tablet

Intervention Type: DRUG

Matching film-coated placebo tablet

Interventions

JNT-517 Suspension

JNT-517 in on-site compounded suspension

Intervention Type: DRUG

Placebo Suspension

On-site compounded placebo suspension

Intervention Type: DRUG

JNT-517 Tablet

JNT-517 tablets, 25 mg and 75 mg

Intervention Type: DRUG

Placebo Tablet

Matching film-coated placebo tablet

Intervention Type: DRUG

Eligibility Criteria

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.

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Otsuka Pharmaceutical Development & Commercialization, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Florida College of Medicine

Gainesville, Florida, United States

University of South Florida

Tampa, Florida, United States

Rare Disease Research

Atlanta, Georgia, United States

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Oregon Health & Sciences University

Portland, Oregon, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

UT Southwestern Medical Center

Dallas, Texas, United States

University of Texas Health Science Center at Houston

Houston, Texas, United States

Utah Health - The University of Utah Hospital

Salt Lake City, Utah, United States

Nucleus Network Melbourne

Melbourne, Melbourne VIC, Australia

Westmead Hospital

Westmead, New South Wales, Australia

Mater Misericordia Ltd

South Brisbane, Queensland, Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Countries

United States; Australia

Other Identifiers

JNT517-101

Identifier Type: -

Identifier Source: org_study_id