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Trial registered on ANZCTR


Registration number
ACTRN12622001065785p
Ethics application status
Submitted, not yet approved
Date submitted
6/07/2022
Date registered
2/08/2022
Date last updated
2/08/2022
Date data sharing statement initially provided
2/08/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Part A: A Study of ABI-2280 Vaginal Tablet in Participants with Cervical Intraepithelial neoplasia
Scientific title
Part A: An Open-Label, Single and Multiple-Dose Study to Evaluate Safety, Tolerability and Efficacy of ABI-2280 Vaginal Tablet in Participants with biopsy-confirmed Cervical Squamous Intraepithelial neoplasia (with visible lesions)
Secondary ID [1] 307407 0
ABI-2280-303
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cervical Squamous Intraepithelial Lesions 326737 0
Condition category
Condition code
Reproductive Health and Childbirth 323970 323970 0 0
Other reproductive health and childbirth disorders
Renal and Urogenital 324212 324212 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Investigational Product (IP): ABI-2280 Vaginal Tablet
Dosage Form: Tablet
Method of Administration: self-administered using a vaginal tablet applicator
Dose: 0.1 mg, 0.3 mg, 1.0 mg
The study consists of three parts
Part A (single dose followed by multiple dose):
Cohort A1: 0.1 mg of single dose ABI-2280 Vaginal tablet on Day 1, Day 8, 10, 12
Cohort A2: 0.3 mg of single dose ABI-2280 Vaginal tablet on Day 1, Day 8, 10, 12
Cohort A3: 1.0 mg of single dose ABI-2280 Vaginal tablet on Day 1, Day 8, 10, 12
The dose of ABI-2280 Vaginal Tablet will be self-administered by participants in clinic under the supervision of Principal Investigator (PI) or qualified designee.
For all cohorts in Part A, participants will be enrolled and will receive the first dose of study drug on Day 1. If the Investigator deems the safety and tolerability at the follow-up visit on Day 8 acceptable, participants will begin multiple dosing in that cohort. Doses for multiple doses for each participant will not exceed what the participant previously received as a single dose.
Enrollment in Cohorts A2 and A3 shall proceed after the Safety Monitoring Committee (SMC) has reviewed the safety data from Day 8 from all three participants, and other available data, of the preceding cohort and has determined it is safe to proceed.
The first dose will be self-administered in the clinic by the participant, with supervision by the Principal Investigator (PI) or qualified designee. The subsequent doses will be self-administered at home.
Participant will complete Patient Diary to confirm self-administration at home.
Each Cohort will enrol distinct group of the participants
Intervention code [1] 323843 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 331783 0
To assess the safety and tolerability of ABI-2280 Vaginal Tablet by the incidence and severity of Adverse events (AEs).
Adverse events (AEs) will be coded using the most current version of Medical Dictionary for Regulatory Activities (MedDRA®)
Timepoint [1] 331783 0
From Baseline to Day 42 post dose administration
Secondary outcome [1] 411108 0
To determine plasma concentrations of ABI-2280 and its metabolite(s) following single and multiple doses of vaginal tablets.
Plasma for measurement of plasma concentrations of ABI-2280 and metabolites will be collected

Pharmacokinetic (PK) parameters:
- Time to maximum observed drug concentration (tmax)
- Maximum observed drug concentration (Cmax)
- Area under the curve (AUC) from time zero to last measurable concentration (AUC0-last)
- AUC from time zero to infinity (AUC8)
- Apparent elimination half-life (t½)
- Apparent terminal elimination rate constant (Kel)
- Apparent clearance (CL/F)
- Apparent volume of distribution at the terminal phase (Vz/F)
Timepoint [1] 411108 0
PK samples should be taken within 60 minutes prior to single dosing on Day 1, and 1 hr (± 5 mins), 2 hrs (± 5 mins), 6 (± 1 hour) post-dose on Day 1. For participants who stay overnight in the clinic on Day 1, a 12-hour (± 1 hour) post dose PK sample will be drawn.
A 24-hour (± 2 hours) post-dose PK sample will be drawn on all participants on Day 2, Day 8, Day 15 and Day 29.
Secondary outcome [2] 411109 0
To assess histopathologic changes in Cervical high-grade squamous intraepithelial lesion (cHSIL) by colposcopy
Timepoint [2] 411109 0
Approximately 12 weeks after the first dose of ABI-2280 Vaginal Tablet.
Secondary outcome [3] 412023 0
To assess histopathologic changes in large loop excision of the transformation zone (LLETZ) specimen
Timepoint [3] 412023 0
Approximately 12 weeks after the first dose of ABI-2280 Vaginal Tablet.

Eligibility
Key inclusion criteria
1. Women, 25 to 55 years old.
2. Participants with biopsy-confirmed CIN (with visible lesions) regardless of p16 positivity may be enrolled upon consultation with PI and medical Monitor. These participants will not be required to get large loop excision of the transformation zone (LLETZ) if not medically necessary, as determined by the PI in consultation with the Medical Monitor.
3. No prior treatment for Cervical intraepithelial neoplasia (CIN).
4. Generally, in good health with no clinically significant pulmonary, cardiac, gastro-enterologic, neurologic, renal, musculoskeletal, rheumatologic, metabolic, neoplastic, or endocrine disease.
5. Willing to use abstinence during the week(s) of study medication administration. In addition, participants agree to take additional strict precautions throughout the study to prevent pregnancy. Under the guidance of the PI, they will be informed of reliable birth control methods to include oral contraceptives and long-acting reversible contraceptive methods. IUDs are acceptable but should be inserted at least 1 month prior to enrollment; however, the use of contraception methods such as a diaphragm, spermicide or Nuvaring® are not allowed.
6. Agree to abstain from activities such as vaginal douching or insertion of any vaginal products other than the investigational product for at least 48 hours prior to enrollment through 7 days after last dose.
7. Generally experiencing regular menstrual cycles (as judged by the PI), unless using long-acting reversible contraception that induces amenorrhea (e.g., Mirena IUD, Norplant).
8. Able and willing to return to the clinic for all study procedures.
9. Able and willing to provide informed consent.
10. Colposcopy is satisfactory based on visualization of the entire squamocolumnar junction (SCJ). The borders of all lesions must be completely visible.
11. If cytology or previous histology suggests the presence of glandular disease, willing to undergo endocervical curettage (ECC) to rule out adenocarcinoma in situ or invasive cancer.
12. The upper limit of the visible (usually aceto-white) lesion is within 3 quadrants or less at screening.
13. Willing to provide access to medical records consisting of HPV test results and pathology reports including p16 results.
14. Able and willing to abstain from sexual intercourse for 48 hours prior to first dose and 48 hours after each dose.
Minimum age
25 Years
Maximum age
55 Years
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Women who are pregnant, plan to become pregnant in the next 4 months, or lactating females.
2. Unwilling to use stringent methods of contraception (including barrier method, as well as another acceptable method) throughout the course of the study.
3. History of cancer, except basal cell or squamous cell carcinoma of the skin.
4. History of genital herpes with outbreak within prior 12 months.
5. Have an active pelvic or non-HPV (Human papillomavirus) vaginal infection (e.g., that was detected by a positive urine screen for gonorrhea or chlamydial infection, bimanual exam consistent with pelvic inflammatory disease, positive bedside testing criteria for bacterial vaginosis, candida vaginitis or trichomonal vaginitis, etc).
6. Current or recent abnormal vaginal discharge and /or abnormal vaginal bleeding.
7. Had a therapeutic abortion or miscarriage less than 3 months prior.
8. Any clinically significant immune suppressing condition.
9. Any medical condition that, in the opinion of the Investigator, would result in increased risk of bleeding at biopsy.
10. Participants with a significant acute condition or any other condition that in the opinion of the Investigator might interfere with the evaluation of the study objectives.
11. Taking any of the following medications: corticosteroids (inhaled and topical corticosteroids are allowed), immunomodulatory treatments, any prescription that in the opinion of the Investigator could interfere with the interpretation of the results or over the counter (OTC) intravaginal preparation within 2 weeks of enrollment (Study Day 1).
12. Hypersensitivity to any component of the product formulation excipients and/or other nucleoside analogues (such as cidofovir, etc.).
13. Participation in any clinical study with an experimental medication or device within 30 days or 5 half-lives (whichever is longer) of enrollment (Study Day 1).
14. Human immunodeficiency virus (HIV) positive (tested at screening visit or tested within 3 months of screening visit).
15. Menses expected to start within 7 days of enrollment (Study Day 1).
16. Vaccination (even 1 dose) with a prophylactic HPV vaccine (i.e. Gardasil®, Gardasil®-9 or Cervarix®) in the last 3 months.
17. Vaccination with a therapeutic HPV vaccine.
18. Biopsy performed more than 60 days prior to enrollment (dosing), unless approved by the Medical Monitor.
19. CIN not amenable to adequate colposcopic evaluations.
20. Women who, in the PI’s judgment, would be harmed by the delay in undergoing definitive treatment as a result of study participation and the ABI-2280 Vaginal Tablet dosing schedule.
21. Resolution of CIN lesion(s) prior to enrollment.
22. ECC positive for glandular disease (adenocarcinoma in situ) or invasive cancer.
23. History of cervical cancer, colposcopy suspicious for cancer, any prior treatment of CIN, or hysterectomy.
24. Plan to have excision or ablation of the lesions, or to undergo LLETZ before the end of the study.
25. Current alcohol or substance abuse as assessed by the PI.

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)
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
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
10/08/2022
Actual
Date of last participant enrolment
Anticipated
12/06/2023
Actual
Date of last data collection
Anticipated
11/09/2023
Actual
Sample size
Target
9
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD
Recruitment hospital [1] 22604 0
Gold Coast University Hospital - Southport
Recruitment hospital [2] 22605 0
East Sydney Doctors - Darlinghurst
Recruitment postcode(s) [1] 37864 0
4215 - Southport
Recruitment postcode(s) [2] 37865 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 311684 0
Commercial sector/Industry
Name [1] 311684 0
Antiva Bioscience, Inc.
Country [1] 311684 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Antiva Bioscience, Inc.
Address
280 Old Country Road #257
Brisbane, CA 94005
Country
United States of America
Secondary sponsor category [1] 313149 0
None
Name [1] 313149 0
Address [1] 313149 0
Country [1] 313149 0
Other collaborator category [1] 282335 0
Commercial sector/Industry
Name [1] 282335 0
Novotech (Australia) Pty Limited
Address [1] 282335 0
Level 3, 235 Pyrmont street, Pyrmont NSW 2009
Country [1] 282335 0
Australia

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 311138 0
Gold Coast Hospital and Health Service HREC
Ethics committee address [1] 311138 0
Ethics committee country [1] 311138 0
Australia
Date submitted for ethics approval [1] 311138 0
13/06/2022
Approval date [1] 311138 0
Ethics approval number [1] 311138 0
Ethics committee name [2] 311146 0
Bellberry Limited
Ethics committee address [2] 311146 0
Ethics committee country [2] 311146 0
Australia
Date submitted for ethics approval [2] 311146 0
13/06/2022
Approval date [2] 311146 0
Ethics approval number [2] 311146 0

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

Contacts
Principal investigator
Name 120074 0
Dr Graeme Walker
Address 120074 0
Gold Coast University Hospital
1 Hospital Boulevard, Southport, QLD, 4215
Country 120074 0
Australia
Phone 120074 0
+61 1300 744 284
Fax 120074 0
Email 120074 0
[email protected]
Contact person for public queries
Name 120075 0
Amy Burks
Address 120075 0
Antiva Biosciences Inc.
280 Old County Road, #257
Brisbane, CA 94005
Country 120075 0
United States of America
Phone 120075 0
+1 650 822 1406
Fax 120075 0
Email 120075 0
[email protected]
Contact person for scientific queries
Name 120076 0
Oranee T. Daniels
Address 120076 0
Antiva Biosciences Inc.
280 Old County Road, #257
Brisbane, CA 94005
Country 120076 0
United States of America
Phone 120076 0
+1 650 822 1408
Fax 120076 0
Email 120076 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


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.