First-in-Human, Multiple Part Clinical Study of JNT-517 in Healthy Participants and in Participants With Phenylketonuria
- Conditions
- Phenylketonuria
- Interventions
- Drug: JNT-517 SuspensionDrug: Placebo SuspensionDrug: JNT-517 TabletDrug: Placebo Tablet
- Registration Number
- NCT05781399
- Lead Sponsor
- Jnana Therapeutics
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 112
Parts A, B, and C:
-
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).
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Non-smoker for at least 2 weeks prior to dosing and willing to abstain during the study.
Part D:
-
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.
Key
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description JNT-517 MAD (Part B) JNT-517 Suspension JNT-517 or placebo once or twice daily for 14 days, with first daily dose given after an overnight fast. JNT-517 MAD (Part B) Placebo Suspension JNT-517 or placebo once or twice daily for 14 days, with first daily dose given after an overnight fast. JNT-517 SAD (Part A) Placebo Suspension Single dose of JNT-517 or placebo in fasted state. JNT-517 Suspension Then Tablet Fasted Then Tablet Fed (Part C) JNT-517 Suspension 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. JNT-517 Tablet Fed Then Suspension Then Tablet Fasted (Part C) JNT-517 Suspension 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. JNT-517 Suspension Then Tablet Fasted Then Tablet Fed (Part C) JNT-517 Tablet 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. JNT-517 Tablet Fasted Then Tablet Fed Then Suspension (Part C) JNT-517 Suspension 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. JNT-517 SAD (Part A) JNT-517 Suspension Single dose of JNT-517 or placebo in fasted state. JNT-517 Tablet Fasted Then Tablet Fed Then Suspension (Part C) JNT-517 Tablet 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. JNT-517 PKU (Part D) JNT-517 Tablet JNT-517 or placebo daily for 4 weeks. Dose is based on data from Parts A, B, and C. JNT-517 Tablet Fed Then Suspension Then Tablet Fasted (Part C) JNT-517 Tablet 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. JNT-517 PKU (Part D) Placebo Tablet JNT-517 or placebo daily for 4 weeks. Dose is based on data from Parts A, B, and C.
- Primary Outcome Measures
Name Time Method Number of participants with treatment-emergent adverse events Parts A and C: Screening to Day 8; Part B: Screening to Day 21; Part D: Screening to Day 35 Reported based on results of 12-lead ECGs, vital signs, clinical laboratory tests, and other medical assessments.
- Secondary Outcome Measures
Name Time Method Time to maximum plasma concentration (Tmax) of JNT-517 Parts A and C: 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: pre-dose to 4 hrs post-dose on Days 1, 14, 28 Plasma terminal half-life (t1/2) of JNT-517 Parts A and C: 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: 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 Part C only
Plasma area under the concentration-time curve (AUC) of JNT-517 Parts A and C: 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: pre-dose to 4 hrs post-dose on Days 1, 14, 28 Maximum observed plasma concentration (Cmax) of JNT-517 Parts A and C: 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: pre-dose to 4 hrs post-dose on Days 1, 14, 28 Comparison of Cmax of JNT-517 in fed and fasted states Pre-dose to 72 hrs post-dose on Day 1 Part C only
Comparison of AUC of JNT-517 in fed and fasted states Pre-dose to 72 hrs post-dose on Day 1 Part C only
Changes in urinary amino acid levels Screening and Days 1, 7, 14, 21, 28 Part D only. Urine samples will be collected at the indicated timepoints and analyzed for amino acid levels, including Phe.
Trial Locations
- Locations (15)
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
UPMC Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
University of Florida College of Medicine
🇺🇸Gainesville, Florida, United States
Rare Disease Research
🇺🇸Atlanta, Georgia, United States
Ann & Robert H. Lurie Children's Hospital of Chicago
🇺🇸Chicago, Illinois, United States
UT Southwestern Medical Center
🇺🇸Dallas, Texas, United States
University of Texas Health Science Center at Houston
🇺🇸Houston, Texas, United States
Mater Misericordia Ltd
🇦🇺South Brisbane, Queensland, Australia
Nucleus Network Melbourne
🇦🇺Melbourne, Melbourne VIC, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Oregon Health & Sciences University
🇺🇸Portland, Oregon, United States
Utah Health - The University of Utah Hospital
🇺🇸Salt Lake City, Utah, United States
University of South Florida
🇺🇸Tampa, Florida, United States
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia