Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622001271796
Ethics application status
Approved
Date submitted
13/09/2022
Date registered
28/09/2022
Date last updated
31/08/2023
Date data sharing statement initially provided
28/09/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
First in human clinical study of a novel drug JNT-517 to assess its safety and tolerability, effects of food intake and to compare JNT-517 levels when taken as an oral suspension and tablet formulation.
Scientific title
A phase 1, first-in-human study to asses the pharmacokinetics of single oral doses of JNT-517 in the fasted and fed states and to evaluate the comparative bioavailability of 2 formulations of JNT-517 in healthy participants.
Secondary ID [1] 307961 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record
This record is a sub-study of ACTRN12622001222730p

Health condition
Health condition(s) or problem(s) studied:
phenylketonuria 327619 0
Condition category
Condition code
Metabolic and Endocrine 324707 324707 0 0
Metabolic disorders
Human Genetics and Inherited Disorders 324708 324708 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This part will be an open-label, 3-period, 3-treatment crossover design to evaluate the food effect and relative bioavailability of 2 formulations of JNT-517 in 12 participants. All participants will be randomised to receive a single dose of 3 treatments listed below in one of these sequences: ABC, BCA, CAB. The dose of JNT-517 will be determined from safety data collected during ACTRN12622001222730p study.
The periods will be separated by a minimum 5 half-lives (2 days).
A - on-site compounded oral suspension in fasted state
B - solid formulation (tablet) in fasted state
C - solid formulation (tablet) in fed state
Participants will be required to fast for a minimum of 8 hours overnight prior to each dosing day. In fasted periods (A and B), participants will remain fasted until 4 hours post dose. In fed period (C) dosing will occur within 30 minutes from the start of the meal. In all periods breakfast should be consumed within a maximum of 30 minutes.
The standardised meal will be the standard US Food and Drug Administration high-fat, high calorie (800 to 1000 calories) breakfast. Approximately 50% of total caloric content of the meal will be from fat. The meal will derive approximately 150, 250, and 500-600 calories from protein, carbohydrate, and fat, respectively.
Healthy volunteers will stay in the clinical research unit for the entire duration of dosing and will take study drug under direct supervision of the clinical research unit staff.
Intervention code [1] 324419 0
Treatment: Drugs
Comparator / control treatment
Crossover arm A (oral suspension in fasted state) will serve as the control treatment.
Control group
Active

Outcomes
Primary outcome [1] 332526 0
Safety and tolerability of single oral dose of JNT-517 in healthy participants through review of:
- treatment-emergent adverse event
- 12-lead electrocardiograms
- vital signs (blood pressure and heart rate assessed by sphygmomanometer, body temperature by thermometer)
- clinical safety laboratory tests: serum chemistry (including liver function tests, electrolytes, kidney function tests, cholesterol and triglycerides), full blood count and coagulation tests will be assessed using whole blood sample, urinalysis will be assessed using urine sample.
Timepoint [1] 332526 0
Adverse events: continuously from admission (Day -1) until discharge on Day 10 and on Day 14
12-lead ECG: Screening (Days -28 to -2), admission (Day -1), Day 3, Day 6, Day 9 and Day 14.
Vital Signs: Screening (Days -28 to -2), admission (Day -1), Day 1 (pre-dose, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs after dose), Day 3, Day 4 (pre-dose, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs after dose), Day 6, Day 7 (pre-dose, 1 hr, 2 hrs, 4 hrs, 6 hrs, 8 hrs after dose), Day 9, Day 14.
Clinical Laboratory Tests: Screening (Days -28 to -2), admission (Day -1), Day 3, Day 6, Day 9, Day 14.
Secondary outcome [1] 413820 0
Pharmacokinetics of single oral doses of JNT-517 in the fasted and fed states through comparison of the time to maximum plasma concentration and the exposure parameters maximum observed plasma concentration and plasma concentration -time curves in the fed and fasted states.
Timepoint [1] 413820 0
Pre-dose, 30 min, 60 min, 1.5 hr, 2 hr, 2.5 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 24 hr, 36 hr, 48 hr, 72 hr after dosing on Day 1 of each 3 treatment periods.
Secondary outcome [2] 413821 0
Comparative bioavailability of 2 formulations of JNT-517 through comparison of the time to maximum plasma concentration and the exposure parameters maximum observed plasma concentration and plasma concentration -time curves.
Timepoint [2] 413821 0
Pre-dose, 30 min, 60 min, 1.5 hr, 2 hr, 2.5 hr, 3 hr, 4 hr, 6 hr, 8 hr, 10 hr, 12 hr, 24 hr, 36 hr, 48 hr, 72 hr after dosing on Day 1 of each 3 treatment periods.

Eligibility
Key inclusion criteria
1. Males and females 18 to 55 years of age, inclusive.
2. Medically healthy with no clinically significant medical history, physical examination, laboratory results, vital signs, or ECGs at Screening and Day 1.
3. Body mass index (BMI) of 18-40 kg/m2 and total body weight >50 kg.
4. Non-smoker for at least 2 weeks prior to dosing and willing to abstain during the study.
5. Females of childbearing potential involved in any sexual intercourse that could lead to pregnancy: the participant must agree to use two highly effective contraceptive methods from Screening until at least 1 week after the last study drug administration.
a. Female participants of childbearing potential must have a negative serum pregnancy test at Screening and a negative urine pregnancy test by Day 1.
6. Females not of childbearing potential or postmenopausal defined as follows:
a. Have had surgical sterilization (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy)
b. Have had amenorrhea for minimum of 1 year with confirmation by levels of follicle stimulating hormone testing
7. For male participants involved in any sexual intercourse that could lead to pregnancy, participant must agree to use highly effective contraceptive methods from Day 1 until at least 12 weeks after the last study drug administration.
Note: No restrictions are required for males who have undergone a documented vasectomy at least 4 months prior to Screening. If vasectomy procedure is not documented or was performed less than 4 months prior to Screening, males must follow the same contraception as for non-vasectomized participants.
8. Participants with psychiatric illness must be well-controlled for last 6 months prior to the Screening visit and if on medication, on stable medications for the last 3 months.
9. Capable of giving signed informed consent and ability to comply with study procedures.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
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. Creatinine clearance <90 mL/min by Cockcroft-Gault formula.
7. Participation in another investigational drug trial within 30 days or, if known, 5 half-lives of the investigational drug (whichever is longer).
8. Alcohol consumption within 5 days of randomization and/or unwilling to abstain during the study.
9. Use of any medications that are inhibitors or inducers of cytochrome P450 (CYP)3A4 or inhibitors of the transporter P-glycoprotein (P-gp) within 4 weeks prior to randomization and unwilling and/or unable to avoid these medications throughout the treatment duration.
10. Use of any medication that is a substrate of CYP3A4, or a substrate of the transporters P-gp, breast cancer resistance protein (BCRP), organic anion transporter 3 (OAT3), multidrug and toxin extrusion (MATE)1, or MATE2-K within 4 weeks prior to randomization and unwilling and/or unable to avoid these medications throughout the treatment duration.
11. History of drug/alcohol abuse in the last year.
12. Inability to tolerate oral medication.
13. Allergy to JNT-517 or any component of the investigational product.
14. Given >50 mL of blood or plasma within 30 days of Screening or >500 mL of blood or plasma within 60 days of Screening.
15. Any of the following laboratory values at the Screening visit:
• Alanine aminotransferase or aspartate aminotransferase values >upper limit of normal (ULN)
• Total bilirubin >ULN
• Haemoglobin <11.0 g/dL (<110.0 g/L)
• White blood cell count <4.5 × 10 9/L (<4500/mm3)
• Platelet count <150 × 10 9/L (<150,000/mm3)
16. Smoker (defined as an individual who has used nicotine-containing products, including cigarettes and e-cigarettes) within the last 2 weeks prior to dosing.
17. Positive for cotinine or drug screen.

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)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
A formal statistical analysis plan will be developed and finalized before database lock.
The sample size of 12 healthy participants has been selected based on the clinical consideration to provide safety and tolerability information and pharmacological considerations with the need to minimise exposure to healthy participants and is in line with other similar Phase 1 studies. No formal sample size calculations have been performed.
Analysis populations:
Safety Population: includes all participants who receive at least one dose of study drug.
PK Population: includes all participants who receive at least one dose of study drug and have at least one evaluable post-dose PK sample.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
7/02/2023
Actual
7/02/2023
Date of last participant enrolment
Anticipated
10/02/2023
Actual
7/02/2023
Date of last data collection
Anticipated
24/02/2023
Actual
21/02/2023
Sample size
Target
12
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 23152 0
Nucleus Network - Melbourne
Recruitment hospital [2] 23153 0
Nucleus Network - Geelong
Recruitment postcode(s) [1] 38510 0
3004 - Melbourne
Recruitment postcode(s) [2] 38511 0
3220 - Geelong

Funding & Sponsors
Funding source category [1] 312228 0
Commercial sector/Industry
Name [1] 312228 0
Jnana Therapeutics, Inc.
Country [1] 312228 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
CTI Clinical Trial and Consulting Services Australia Pty Ltd.
Address
Level 21, 207 Kent Street, Sydney NSW 2000
Country
Australia
Secondary sponsor category [1] 313763 0
None
Name [1] 313763 0
Address [1] 313763 0
Country [1] 313763 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311607 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 311607 0
Ethics committee country [1] 311607 0
Australia
Date submitted for ethics approval [1] 311607 0
22/08/2022
Approval date [1] 311607 0
04/10/2022
Ethics approval number [1] 311607 0
Project No: 481/22 (HREC/89403/Alfred-2022)

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 121694 0
Dr Ofer Gonen
Address 121694 0
Nucleus Network Melbourne,
Level 5, Burnett Tower,
89 Commercial Road,
Melbourne VIC 3004
Country 121694 0
Australia
Phone 121694 0
+61 3 8593 9800
Fax 121694 0
Email 121694 0
[email protected]
Contact person for public queries
Name 121695 0
Ofer Gonen
Address 121695 0
Nucleus Network Melbourne,
Level 5, Burnett Tower,
89 Commercial Road,
Melbourne VIC 3004
Country 121695 0
Australia
Phone 121695 0
+61 3 8593 9800
Fax 121695 0
Email 121695 0
[email protected]
Contact person for scientific queries
Name 121696 0
Toby Vaughn
Address 121696 0
Jnana Therapeutics, Inc.
6 Tide Street, Suite 301,
Boston MA 02210
Country 121696 0
United States of America
Phone 121696 0
+1 513 5050770
Fax 121696 0
Email 121696 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
The data will be analysed in aggregate and reported as such to the PI, participants if interested, clinical community (via public disclosure in presentations, publications, investigator brochure and other public forums), to regulatory authorities by regulatory filings on this trial and related future trials, and to the investor community at private and public meetings. There will be no patient identifier data attached to any of the aggregate data. The only place the patient name can be associated with the data is at the site where the original enrolment occurs. After enrolment, all data entry is based on an anonymized patient identifier.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.