Clinical trial NCT05781399: First-in-Human, Multiple Part Clinical Study of JNT-517 in Healthy Participants and in Participants With Phenylketonuria
Official title: A Phase 1, First-In-Human, Multiple Part, Single Ascending and Multiple Dose Study of JNT-517 in Healthy Participants and in Participants With Phenylketonuria
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Phenylketonuria
Keywords: PKU
Lead sponsor: Jnana Therapeutics
Sponsor class: INDUSTRY
First posted: 2023-03-23
Enrollment: 112
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
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

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.


Eligibility criteria: Key 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.

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.

Primary outcomes:
measure: Number of participants with treatment-emergent adverse events
timeFrame: Parts A and C: Screening to Day 8; Part B: Screening to Day 21; Part D: Screening to Day 35
Secondary outcomes:
measure: Plasma area under the concentration-time curve (AUC) of JNT-517
timeFrame: 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
measure: Maximum observed plasma concentration (Cmax) of JNT-517
timeFrame: 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
measure: Time to maximum plasma concentration (Tmax) of JNT-517
timeFrame: 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
measure: Plasma terminal half-life (t1/2) of JNT-517
timeFrame: 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
measure: Comparison of Tmax of JNT-517 in fed and fasted states
timeFrame: Pre-dose to 72 hrs post-dose on Day 1
measure: Comparison of Cmax of JNT-517 in fed and fasted states
timeFrame: Pre-dose to 72 hrs post-dose on Day 1
measure: Comparison of AUC of JNT-517 in fed and fasted states
timeFrame: Pre-dose to 72 hrs post-dose on Day 1
measure: Changes in urinary amino acid levels
timeFrame: Screening and Days 1, 7, 14, 21, 28
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: University of Florida College of Medicine
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
city: Atlanta
country: United States
facility: Rare Disease Research
state: Georgia
city: Chicago
country: United States
facility: Ann & Robert H. Lurie Children's Hospital of Chicago
state: Illinois
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Portland
country: United States
facility: Oregon Health & Sciences University
state: Oregon
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Children's Hospital of Pittsburgh
state: Pennsylvania
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Salt Lake City
country: United States
facility: Utah Health - The University of Utah Hospital
state: Utah
city: Melbourne
country: Australia
facility: Nucleus Network Melbourne
state: Melbourne VIC
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: South Brisbane
country: Australia
facility: Mater Misericordia Ltd
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
Study officials:
References: