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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05781399




Registration number
NCT05781399
Ethics application status
Date submitted
11/02/2023
Date registered
23/03/2023
Date last updated
12/01/2024

Titles & IDs
Public title
First-in-Human, Multiple Part Clinical Study of JNT-517 in Healthy Participants and in Participants With Phenylketonuria
Scientific 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
Secondary ID [1] 0 0
JNT517-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Phenylketonuria 0 0
Condition category
Condition code
Metabolic and Endocrine 0 0 0 0
Other metabolic disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - JNT-517 Suspension
Treatment: Drugs - Placebo Suspension
Treatment: Drugs - JNT-517 Tablet
Treatment: Drugs - Placebo Tablet

Experimental: JNT-517 SAD (Part A) - Single dose of JNT-517 or placebo in fasted state.

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.

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.


Treatment: Drugs: JNT-517 Suspension
JNT-517 in on-site compounded suspension

Treatment: Drugs: Placebo Suspension
On-site compounded placebo suspension

Treatment: Drugs: JNT-517 Tablet
JNT-517 tablets, 25 mg and 75 mg

Treatment: Drugs: Placebo Tablet
Matching film-coated placebo tablet
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants with treatment-emergent adverse events
Timepoint [1] 0 0
Parts A and C: Screening to Day 8; Part B: Screening to Day 21; Part D: Screening to Day 35
Secondary outcome [1] 0 0
Plasma area under the concentration-time curve (AUC) of JNT-517
Timepoint [1] 0 0
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 outcome [2] 0 0
Maximum observed plasma concentration (Cmax) of JNT-517
Timepoint [2] 0 0
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 outcome [3] 0 0
Time to maximum plasma concentration (Tmax) of JNT-517
Timepoint [3] 0 0
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 outcome [4] 0 0
Plasma terminal half-life (t1/2) of JNT-517
Timepoint [4] 0 0
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 outcome [5] 0 0
Comparison of Tmax of JNT-517 in fed and fasted states
Timepoint [5] 0 0
Pre-dose to 72 hrs post-dose on Day 1
Secondary outcome [6] 0 0
Comparison of Cmax of JNT-517 in fed and fasted states
Timepoint [6] 0 0
Pre-dose to 72 hrs post-dose on Day 1
Secondary outcome [7] 0 0
Comparison of AUC of JNT-517 in fed and fasted states
Timepoint [7] 0 0
Pre-dose to 72 hrs post-dose on Day 1
Secondary outcome [8] 0 0
Changes in urinary amino acid levels
Timepoint [8] 0 0
Screening and Days 1, 7, 14, 21, 28

Eligibility
Key inclusion criteria
Key

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
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/10/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2025
Actual
Sample size
Target
112
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Melbourne VICNSW,QLD,SA
Recruitment hospital [1] 0 0
Nucleus Network Melbourne - Melbourne
Recruitment hospital [2] 0 0
Westmead Hospital - Westmead
Recruitment hospital [3] 0 0
Mater Misericordia Ltd - South Brisbane
Recruitment hospital [4] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
4101 - South Brisbane
Recruitment postcode(s) [4] 0 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Florida
Country [2] 0 0
United States of America
State/province [2] 0 0
Georgia
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Nebraska
Country [5] 0 0
United States of America
State/province [5] 0 0
Oregon
Country [6] 0 0
United States of America
State/province [6] 0 0
Pennsylvania
Country [7] 0 0
United States of America
State/province [7] 0 0
Texas
Country [8] 0 0
United States of America
State/province [8] 0 0
Utah

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Jnana Therapeutics
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05781399
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toby Vaughn
Address 0 0
Country 0 0
Phone 0 0
1-513-505-0770
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05781399