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Trial registered on ANZCTR


Registration number
ACTRN12622001222730
Ethics application status
Approved
Date submitted
22/08/2022
Date registered
9/09/2022
Date last updated
14/01/2024
Date data sharing statement initially provided
9/09/2022
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 in healthy volunteers
Scientific title
A phase 1, first-in-human, single ascending and multiple dose study of JNT-517 in healthy participants.
Secondary ID [1] 307763 0
JNT517-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Phenylketonuria 327370 0
Condition category
Condition code
Metabolic and Endocrine 324493 324493 0 0
Metabolic disorders
Human Genetics and Inherited Disorders 324649 324649 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Part A is a single ascending dose part of the study in healthy volunteers. It will consist of up to 5 sequential cohorts of 8 participants each. In each cohort, participants will be randomised to receive a single dose of JNT-517 or placebo in a 3:1 ratio (6 participants will receive JNT-517 and 2 - placebo) in a fasted state and in a double-blinded fashion. JNT-517 and placebo will be administered as a suspension orally. The starting dose will be 25 mg of JNT-517. The maximum dose dose will not exceed 240 mg. The maximum dose escalation between cohorts will be no more than 3-fold. A dose level may be repeated or decreased, or a new dose cohort added as required, based on emerging results. Dose escalation to a consecutive higher exposure dose regiment, or to a consecutive study part at the same or lower dose, 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.
Part B is a multiple ascending doses part of the study in healthy volunteers. Enrolment in Part B is expected to commence between 5 and 6 weeks after commencement of Part A. It is expected that up to 3 cohorts of 8 participants each will be enrolled. Doses of JNT-517 in Part B will be selected based on blinded review of safety data of single doses in Part A. In each cohort participants will be randomised in double-blinded fashion to receive JNT-517 or placebo in a 3:1 ratio. Participants will receive JNT-517 or matching placebo BID (twice daily) as oral suspension for 14 consecutive days. Morning dose will be administered after an overnight fast (at least 8 hours) and evening dose will be administered between 8 hours and 8 hours and 15 minutes after the morning dose. An additional fourth cohort can be added, during which 8 participants will receive JNT-517 or placebo in a 3:1 ratio once daily for 14 consecutive days.
Inclusion and exclusion criteria for Parts A and B are identical. In both parts 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] 324254 0
Treatment: Drugs
Comparator / control treatment
Avicel PH-102, microcrystalline cellulose, will be used as placebo in doses corresponding to the dose of JNT-517.
Control group
Placebo

Outcomes
Primary outcome [1] 332321 0
Safety and tolerability of single and multiple oral doses 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] 332321 0
Part A
Adverse events: continuously from admission (Day -1) until 72 hours after dosing and on Day 8.
12 lead ECG: Screening (Days -28 to -2), admission (Day -1), 2 hr, 6 hr, 26 hr, 72 hr after dosing and on Day 8.
Vital signs: Screening (Days -28 to -2), admission (Day -1), pre-dose, 2 hr, 4 hr, 6 hr, 8 hr, 24 hr, 26 hr, 72 hr after dosing and on Day 8.
Clinical Laboratory tests: Screening (Days -28 to -2), admission (Day -1), 8 hr, 24 hr and 72 hr after dosing and on Day 8.
Part B
Adverse events: continuously from admission (Day -1) until discharge on Day 15 and on Day 21
12-lead ECG: Screening (Days -28 to -2), admission (Day -1), Day 14 and Day 21
Vital Signs: Screening (Days -28 to -2), admission (Day -1), then daily until discharge on Day 15, Day 21
Clinical Laboratory Tests: Screening (Days -28 to -2), admission (Day -1), Day 1, Day 3, Day 5, Day 7, Day 10, Day 14 and Day 21.
Secondary outcome [1] 413021 0
Pharmacokinetics of single and multiple oral doses of JNT-517 in healthy participants (Parts A & B) through assessment of plasma concentration-time curves, maximum observed plasma concentration, time to maximum plasma concentration, and terminal half-life.
Timepoint [1] 413021 0
Part A: pre-dose, 0.5 hr, 1 hr, 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. post dosing on Day 1.
Part B: Days 1 & 14 of dosing - pre-dose, 0.5 hr, 1 hr, 1.5 hr, 2 hr, 2.5 hr, 3 hr, 4 hr, 6 hr, 8 hr, 8.5 hr, 9 hr, 9.5 hr, 10 hr, 10.5 hr, 11 hr, 12 hr, 14 hr, 16 hr, 24 hr. Days 3 to 13 - pre-dose (morning). Plasma amino acids pre-dose (morning) Days 1, 7 & 14.

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
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. 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
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
Single group
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.
Analysis populations
For all populations, participant data will be analysed according to the actual intervention received.
Safety Population: includes all participants who receive at least one dose of study drug (JNT-517 or placebo).
PK Population: includes all participants who receive at least one dose of study drug and have at least one evaluable post-dose PK sample.
PD Population: includes all participants who receive at least one dose of study drug and for whom at least one post-dose PD sample is obtained and analysed.
Sample size considerations: A total of 64 healthy participants. The sample size for healthy participants is based on the clinical consideration to provide safety and tolerability information and pharmacological considerations with the need to minimize exposure to healthy participants at each dose level, and is in line with other similar Phase 1 studies.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
31/10/2022
Actual
31/10/2022
Date of last participant enrolment
Anticipated
14/03/2023
Actual
11/10/2023
Date of last data collection
Anticipated
17/10/2023
Actual
12/11/2023
Sample size
Target
72
Accrual to date
Final
72
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 22980 0
Nucleus Network - Melbourne
Recruitment hospital [2] 22981 0
Nucleus Network - Geelong
Recruitment postcode(s) [1] 38290 0
3004 - Melbourne
Recruitment postcode(s) [2] 38291 0
3220 - Geelong
Recruitment outside Australia
Country [1] 24959 0
United States of America
State/province [1] 24959 0

Funding & Sponsors
Funding source category [1] 312031 0
Commercial sector/Industry
Name [1] 312031 0
Jnana Therapeutics, Inc.
Country [1] 312031 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] 313571 0
None
Name [1] 313571 0
Address [1] 313571 0
Country [1] 313571 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 311449 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 311449 0
The Alfred, 55 Commercial Road, Melbourne VIC 3004
Ethics committee country [1] 311449 0
Australia
Date submitted for ethics approval [1] 311449 0
22/08/2022
Approval date [1] 311449 0
04/10/2022
Ethics approval number [1] 311449 0
Project No: 481/22 (HREC/89403/Alfred-2022)

Summary
Brief summary
This will be a Phase 1 first-in-human (FIH) study in 2 parts to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of JNT-517 at various incremental doses administered as single and multiple doses in healthy volunteers.
The study will begin with a single ascending dose portion (Part A) followed by the multiple ascending dose portion (Part B) in healthy volunteers in Australia to evaluate the safety, tolerability, PK, and PD of JNT-517 at various incremental doses.
Trial website
Trial related presentations / publications
Public notes
Additional exclusion criteria are:
- 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.

Contacts
Principal investigator
Name 121130 0
Dr Ofer Gonen
Address 121130 0
Nucleus Network Melbourne,
Level 5, Burnett Tower,
89 Commercial Road,
Melbourne VIC 3004
Country 121130 0
Australia
Phone 121130 0
+61 3 8593 9800
Fax 121130 0
Email 121130 0
[email protected]
Contact person for public queries
Name 121131 0
Ofer Gonen
Address 121131 0
Nucleus Network Melbourne,
Level 5, Burnett Tower,
89 Commercial Road,
Melbourne VIC 3004
Country 121131 0
Australia
Phone 121131 0
+61 3 8593 9800
Fax 121131 0
Email 121131 0
[email protected]
Contact person for scientific queries
Name 121132 0
Toby Vaughn
Address 121132 0
Jnana Therapeutics, Inc.
6 Tide Street, Suite 301,
Boston MA 02210
Country 121132 0
United States of America
Phone 121132 0
+1 513 5050770
Fax 121132 0
Email 121132 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

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