First-in-Human, Multiple Part Clinical Study of JNT-517 in Healthy Participants and in Participants With Phenylketonuria
Purpose
The goal of Parts A and B of this Phase 1, 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 4 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 1b in participants with PKU (4 weeks)-randomized, double-blind, placebo-controlled In each part, participants will complete a Screening Period, a Treatment Period, and a Follow-up Period for safety.
Condition
- Phenylketonuria
Eligibility
- Eligible Ages
- Between 18 Years and 65 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
Parts A, B, and C: 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: 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.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential Assignment
- Intervention Model Description
- The study will be conducted in 4 parts: Parts A, B, C, and D. This study will be seamless, meaning various study parts could begin while other parts are still ongoing, but dose escalation will occur only after satisfactory review of safety and tolerability data from a minimum of 6 participants completing through Day 3, and available PK data.
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
- Masking Description
- Parts A, B, and D are blinded. Part C is open-label.
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental JNT-517 SAD (Part A) |
Single dose of JNT-517 or placebo in fasted state. |
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|
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. |
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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. |
|
|
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. |
|
|
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. |
|
|
Experimental JNT-517 PKU (Part D) |
JNT-517 or placebo daily for 4 weeks. Dose is based on data from Parts A, B, and C. |
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Recruiting Locations
Houston, Texas 77030
More Details
- Status
- Recruiting
- Sponsor
- Jnana Therapeutics