Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000667718p
Ethics application status
Submitted, not yet approved
Date submitted
20/04/2022
Date registered
6/05/2022
Date last updated
8/11/2022
Date data sharing statement initially provided
6/05/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A Study of JT001 Tablets in Caucasian Healthy Subjects after Oral Administrations
Scientific title
An Open-label, Dose-Escalation, Multiple-Dose Phase 1 Clinical Study to Evaluate the Pharmacokinetics, Safety and Tolerability of JT001 Tablets in Caucasian Healthy Subjects after Oral Administrations
Secondary ID [1] 306798 0
JT001-005-I
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 325862 0
Condition category
Condition code
Infection 323182 323182 0 0
Other infectious diseases
Respiratory 323183 323183 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
JT001 is a triisobutyrate prodrug of a nucleoside analogue. The JT001 acts on the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2 in the active form of the nucleoside triphosphate of (116-NTP, di-tri-n-butylamine salt).
Investigational Product: JT001 (VV116)
Mode of Administration: Oral
Method of administration: Oral tablet
Dosage: 200mg, 400mg, 600mg

Dosin frequency: In all dosing group the participants will be administered orally twice a day (approximately 12 hours apart) for 6 consecutive days and the last administration will be given in the morning on Day 6. All doses must be taken under fasting condition.

The study consists of three dosing group as listed below
Cohort 1: 200mg, approximately 9 participants will be enrolled
Cohort 2: 400 mg, approximately 9 participants will be enrolled
Cohort 3: 600mg approximately 9 participants will be enrolled
All doses will be administered at the Clinical Research Unit (CRU) in the presence of the Investigator or their designee, and the oral cavity and drug container will be checked by Investigator or their designee after the subject swallow the IP.
The safety data in all three-dosing group will be reviewed by Safety Review Committee after the completion of each dose group and based on that the dose escalation can be made.
Intervention code [1] 323274 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 330952 0
To explore the pharmacokinetics of JT001 and its prominent metabolite 116-N1 in Caucasian healthy subjects
Blood samples will be collected for pharmacokinetics assessment
Pharmacokinetic (PK) parameters:
• Peak concentration (Cmax)
• Time to peak (Tmax)
• Trough concentration (Ctrough)
• Area under the plasma concentration-time curves (AUC0-t, AUC0-8, and AUC0-t)
• Elimination half-life (t1/2)
• Apparent clearance (CL/F)
• Mean residence time (MRT)
• Apparent volume of distribution (Vz/F)
• Accumulation ratio (Rac)
Timepoint [1] 330952 0
Day 1: blood samples should be collected within 1 h before the first administration, and at 10 min ± 2 min, 20 min ± 2 min, 30 min ± 2 min, 45 min ± 2 min, 1 h ± 2 min, 1.5 h ± 2 min, 2 h ± 2 min, 3 h ± 2 min, 4 h ±2 min, 6 h ± 10 min, 8 h ± 10 min, and 12 h ± 10 min post dose;
Day 5: blood samples should be collected within 0.5 h before each administration;
Day 6: blood samples should be collected within 0.5 h pre-dose, and at 10 min ± 2 min, 20 min ± 2 min, 30 min ± 2 min, 45 min ± 2 min, 1 h ± 2 min, 1.5 h ± 2 min, 2 h ± 2 min, 3 h ± 2 min, 4 h ± 2 min, 6 h ± 10 min, 8 h ± 10 min, 12 h ± 10 min, 24 h ± 10 min, and 48 h ± 1 h post dose
Secondary outcome [1] 408241 0
To evaluate the safety and tolerability of JT001 tablets in Caucasian healthy subjects after multiple doses oral administrations.
To be assessed by monitoring
1. Drug-related adverse events graded according to Common Terminology Criteria for Adverse Events [CTCAE] 5.0
2. Vital signs includes including respiration, blood pressure, body temperature, and pulse will be measure as single recordings using a vital signs monitor at all time-points required per Protocol. If Clinically indicated the Medical Officer may request additional vital signs monitoring as needed.
3. Laboratory tests (hematology, biochemistry, coagulation, and urinalysis)
4. Physical examinations includes general appearance, head, ears, eyes (Ophthalmology tests), nose, throat, dentition, thyroid, chest (heart, lungs), abdomen, skin, neurological, extremities, back, neck, musculoskeletal, and lymph nodes.
5. 12-lead electrocardiograms (heart rate, P-R interval, and QTcF interval)
Timepoint [1] 408241 0
Once daily from baseline to Day 12 post dose

Eligibility
Key inclusion criteria
1. Healthy Caucasian male or female (excluding Middle East) subjects aged 18 to 55 years (inclusive at the time of informed consent). Caucasians are defined as subjects who have 2 parents of Caucasian/European ancestry and 4 grandparents of Caucasian/European ancestry.
2. Subjects must have a Body Mass Index (BMI) greater than 18.0 and equal to or less than 32.0 kg/m2 at Screening with Body weight: male more than 50 kg, female more than 45 kg.
3. Subjects must be in good general health, have no clinically significant abnormalities on vital signs, physical examination, laboratory test, ophthalmology, ECG and B-ultrasonography at Screening and/or before administration of the initial dose of the study drug.
4. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test within 24 hours prior to the start of study drug and must not be breastfeeding, lactating or planning pregnancy during the study period. WOCBP are defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) and is not postmenopausal. Menopause is defined as 12 months of amenorrhea in the absence of other biological causes. In addition, females under the age of 55 years must have a documented serum follicle stimulating hormone (FSH) level greater than 40mIU/mL to confirm menopause. Male participants with potentially postmenopausal partners who are under the age of 55 years must use condoms unless their partner’s postmenopausal status has been confirmed by FSH level.
WOCBP who are not exclusively in same-sex relationships and males with partners of child-bearing potential must agree to use adequate contraception. For WOCBP, contraception should be continued for 32 days after the final dose of study drug. For males, contraception should be continued for 92 days after the final dose of study drug. In addition, males must not donate sperm for 92 days after the final dose.
Males and WOCBP who are continuously not heterosexually active are exempt from contraceptive requirements. However, WOCBP must still undergo pregnancy testing as per protocol.
Investigators will counsel WOCBP and male participants who are sexually active with WOCBP on the importance of pregnancy prevention and the implications of an unexpected pregnancy. Investigators will advise on the use of an adequate methods of contraception, which is defined as use of a condom by the male partner combined with use of a highly effective method of contraception by the female partner. A highly effective method of contraception is one that has a failure rate of less than 1% when used consistently and correctly. Male participants must inform their female partners who are WOCBP of the contraceptive requirements of the protocol and are expected to adhere to using contraception with their partner.
Highly effective methods of contraception are listed below:
• Hormonal methods of contraception including oral contraceptives containing combined estrogen and progesterone, a vaginal ring, injectable and implantable hormonal contraceptives, intrauterine hormone-releasing system (e.g. Mirena) and progestogen-only hormonal contraception associated with inhibition of ovulation
• Nonhormonal intrauterine device (IUD)
• Bilateral tubal occlusion
• Vasectomised subject/partner with documented azoospermia 90 days after procedure, if that partner is the sole sexual partner.
For female participants, include wording that hormonal contraceptives should begin at least 1 month prior to screening to ensure contraceptive is in full effect.
Complete abstinence, defined as the complete avoidance of heterosexual intercourse - is an acceptable form of contraception if used consistently throughout the duration of study and for the durations after dosing specified for males and females above. It is not necessary to use any other method of contraception when complete abstinence is elected. WOCBP who choose complete abstinence must continue to have pregnancy tests as per protocol. The reliability of sexual abstinence needs to be evaluated by the Investigator in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject.
5. Subjects must be willing and able to provide written informed consent after the nature of the study has been explained and before the commencement of any study procedures.
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Known history of allergy to the study drug.
2. History of severe allergic or anaphylactic reactions.
3. Subjects with confirmed diseases in the central nervous system, cardiovascular system, digestive system, respiratory system, urinary system, blood system, metabolic disorders, etc., and require medical intervention, or other diseases that are not suitable for participating in clinical studies (such as psychiatric history, etc.). Subjects with mild depression and anxiety may be enrolled if stable and not medicated.
4. Medical history considered by the Investigator to impact the assessment of PK profiles.
5. Blood donation or blood loss more than 400 mL before screening or has used blood products. Subjects who have donated blood within 1 month or plasma donation within 7 days of Screening will not be included in the study.
6. Subjects who have received treatment with another investigational drug within 3 months of screening or is participating in another study at the time of screening.
7. Use of any prescription drugs, over the counter (OTC) medication, herbal remedies, supplements, or vitamins within 1 week before screening. Taking paracetamol (up to 2000 mg/day) is allowed.
8. Subjects with alcohol addiction within 1 year before screening, defined as drinking more than 14 units per week (1 unit is equivalent to approximately 200 mL of beer with 5% alcohol content, or 25 mL of spirits with 40% alcohol content, or 85 mL of wine with 12% alcohol content).
9. Subjects who have a history of smoking more than 10 cigarettes a day or the equivalent amount within 1 year before screening will not be included. Light smoking (e.g., 10 cigarettes/week) within 1 month prior to screening is acceptable as long as the participant is willing to abstain from smoking during inpatient stay.
10. Subject is unwilling to abstain from smoking or alcohol during the study.
11. Positive test for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (Anti-HCV), Treponema pallidum antibody, and human immunodeficiency virus (HIV) antibody at Screening.
12. Subjects with abnormal ALT or AST value that is considered clinically by the Investigator at Screening will not be included in the study.
13. Glomerular filtration rate (eGFR) less than lower limit of normal (LLN) at Screening. The CKD-EPI formula will be used for the eGFR calculation.
14. Abnormal ECG findings considered by the Investigator to be clinically significant, single-examination QTcF (heart rate corrected) more than 450 ms in males and more than 470 ms in females, and/or other clinically significant abnormalities at Screening.
15. Pregnant or lactating at Screening or planning to become pregnant (self or partner) from Screening until 3 months after the last administration of the study drug.
16. Subject is considered to have other factors, in the opinion of the Investigator, which would make it unlikely that the subject will comply with the protocol or complete the study per protocol.
17. Subjects who received any COVID-19 vaccination within 14 days prior to the first administration of the study drug will not be included in the study.
18. Any other condition that would, in the Investigator's judgement, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures or interpretation of study results.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Sponsor's change of business strategy
Date of first participant enrolment
Anticipated
1/06/2022
Actual
Date of last participant enrolment
Anticipated
18/07/2022
Actual
Date of last data collection
Anticipated
22/07/2022
Actual
Sample size
Target
27
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 22097 0
Nucleus Network - Melbourne
Recruitment hospital [2] 22098 0
Nucleus Network - Geelong
Recruitment postcode(s) [1] 37220 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 311136 0
Commercial sector/Industry
Name [1] 311136 0
Shanghai Vinnerna BioSciences Co., Ltd
Country [1] 311136 0
China
Primary sponsor type
Commercial sector/Industry
Name
Shanghai Vinnerna BioSciences Co., Ltd
Address
Floor 3, Building 1, No.400, Fangchun Road, China (Shanghai) Pilot Free Trade Zone, Shanghai, Postal code: 201203, China
Country
China
Secondary sponsor category [1] 312479 0
None
Name [1] 312479 0
Address [1] 312479 0
Country [1] 312479 0
Other collaborator category [1] 282233 0
Commercial sector/Industry
Name [1] 282233 0
Novotech (Australia) Pty Limited
Address [1] 282233 0
Level 3, 235 Pyrmont street, Pyrmont NSW 2009
Country [1] 282233 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 310662 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 310662 0
55 Commercial Rd, Melbourne VIC 3004
Ethics committee country [1] 310662 0
Australia
Date submitted for ethics approval [1] 310662 0
12/04/2022
Approval date [1] 310662 0
Ethics approval number [1] 310662 0

Summary
Brief summary
This is a phase I, open-label, dose-escalation, multiple-dose study to investigate pharmacokinetics and safety of JT001 in Caucasian healthy subjects.
The study consists of three dose level (200, 400, 600 mg). and the participant will be sequentially assigned from low-dose group to high-dose group to receive the JT001 at one of the three doses according to the dose escalation scheme.
The total duration of participants in the study will be of 14 to 26 days. The study includes a screening phase (up to 14 days), a 6-day multiple-dose phase (D1-D6), a 3-day safety observation phase (end of administration) and 4-day safety follow up period.
Total approximately 27 participants will be enrolled in the study. Each group of dose level will enroll approximately 9 participants.
Oversight of the study will be provided by a committee (the Safety Review Committee) comprising a representative of the Sponsor or Sponsor’s designee, the investigator, and the medical monitor.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 118438 0
Dr Philip Ryan
Address 118438 0
Nucleus Network Pty Ltd
Level 5, Burnet Tower, 89 Commercial Rd, Melbourne 3004, Victoria
Country 118438 0
Australia
Phone 118438 0
+61 03 8593 9800
Fax 118438 0
Email 118438 0
p.ryan@nucleusnetwork.com.au
Contact person for public queries
Name 118439 0
Dr Philip Ryan
Address 118439 0
Nucleus Network Pty Ltd
Level 5, Burnet Tower, 89 Commercial Rd, Melbourne 3004, Victoria
Country 118439 0
Australia
Phone 118439 0
+61 03 8593 9800
Fax 118439 0
Email 118439 0
p.ryan@nucleusnetwork.com.au
Contact person for scientific queries
Name 118440 0
Mr Hao Zhang
Address 118440 0
Protech Pharmaservices Corp China Group,
Flat 801, Block A, China Overseas International Centre, No. 838 South Huang Pi Road, Huangpu District, Shanghai, postal code 200025, China
Country 118440 0
China
Phone 118440 0
+86 21 53687600
Fax 118440 0
Email 118440 0
hao.zhang@ppccro.com

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.