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

Phenylketonuria Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05781399
• Other study ID #: JNT517-101
• Status: Recruiting
• Phase: Phase 1
• Start date: October 31, 2022
• Est. completion date: March 2025

Study information

• Verified date: January 2024
• Source: Jnana Therapeutics
• Contact: Toby Vaughn
• Phone: 1-513-505-0770
• Email: tvaughn[@]jnanatx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 112
• Est. completion date: March 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Phenylketonuria
• Phenylketonurias

Intervention

Drug:
• JNT-517 Suspension
JNT-517 in on-site compounded suspension
• Placebo Suspension
On-site compounded placebo suspension
• JNT-517 Tablet
JNT-517 tablets, 25 mg and 75 mg
• Placebo Tablet
Matching film-coated placebo tablet

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Nucleus Network Melbourne	Melbourne	Melbourne VIC
Australia	Mater Misericordia Ltd	South Brisbane	Queensland
Australia	Westmead Hospital	Westmead	New South Wales
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 Florida College of Medicine	Gainesville	Florida
United States	University of Texas Health Science Center at Houston	Houston	Texas
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
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

Sponsors (1)

Lead Sponsor	Collaborator
Jnana Therapeutics

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 and C: Screening to Day 8; Part B: Screening to Day 21; Part D: Screening to Day 35
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Comparison of Tmax of JNT-517 in fed and fasted states	Part C only	Pre-dose to 72 hrs post-dose on Day 1
Secondary	Comparison of Cmax of JNT-517 in fed and fasted states	Part C only	Pre-dose to 72 hrs post-dose on Day 1
Secondary	Comparison of AUC of JNT-517 in fed and fasted states	Part C only	Pre-dose to 72 hrs post-dose on Day 1
Secondary	Changes in urinary amino acid levels	Part D only. Urine samples will be collected at the indicated timepoints and analyzed for amino acid levels, including Phe.	Screening and Days 1, 7, 14, 21, 28