Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12621001540808
Ethics application status
Approved
Date submitted
23/09/2021
Date registered
11/11/2021
Date last updated
25/05/2022
Date data sharing statement initially provided
11/11/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
A Single and Multiple Dose Escalation Study in Healthy Participants to Evaluate Safety, Tolerability and Pharmacokinetics of ABI-2280 Vaginal Gel and Tablets as Applied to the Cervix
Scientific title
A randomized, Double-blind, Placebo-controlled, Single and Multiple Dose Escalation Study in Healthy Participants to Evaluate Safety, Tolerability and Pharmacokinetics of ABI-2280 Vaginal Gel and Tablet as Applied to the Cervix
Secondary ID [1] 305374 0
ABI-2280-301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cervical High grade squamous Intraepithelial Lesion 323727 0
Condition category
Condition code
Infection 321255 321255 0 0
Other infectious diseases
Renal and Urogenital 321663 321663 0 0
Other renal and urogenital disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a randomized, double-blind, placebo-controlled, single and multiple dose
escalation first-in-human study in healthy female participants. The study is designed to assess the safety, tolerability and PK of ABI-2280 Vaginal Gel and Tablet, applied to the cervix of healthy participants. Participants who meet all inclusion and none of the exclusion criteria will be evaluated throughout the study.
The study will be conducted in 2 parts: Part A (single ascending dose) and Part B (multiple ascending dose).
Investigational Product (IP): ABI-2280
Presentation: Vaginal Gel and Vaginal Tablet
Mode of administration: Intravaginal on the cervix
Part A
Up to approximately 32 participants will be enrolled in one of four cohorts-A1 to A4. Each cohort will consist of 8 participants (6 to receive a single dose of ABI-2280 and 2 to receive a single dose of placebo). No participant will be enrolled in more than one cohort. For all cohorts in Part A, two sentinel participants will be enrolled.
Cohort A1: Participants will receive ABI-2280 vaginal gel, 0.01% or placebo gel
Cohort A2: Participants will receive ABI-2280 vaginal gel, 0.03% or placebo gel
Cohort A3: Participants will receive ABI-2280 vaginal gel 0.1% or placebo gel OR
Cohort A3: Participant will receive ABI-2280 vaginal tablet, up to 0.3 mg or placebo tablet
Cohort A4: Participants will receive ABI-2280 vaginal tablet, up to 1 mg or placebo tablet
Dose levels in part A are: 0.01%, 0.03%, 0.1% of ABI-2280 vaginal gel or placebo gel
and Vaginal tablet up to 0.3 mg and 1 mg of ABI-2280 or Placebo tablet
Part B
Up to approximately 16 participants will be enrolled into two cohorts-B1 and B2. Each cohort will consists of 8 participants (6 to receive ABI-2280 vaginal tablet and 2 to receive placebo).
The following treatments are planned:
Cohort B1: ABI-2280 Vaginal tablet, up to 0.3 mg or placebo tablet administered 3 times over a 1 week period.
Cohort B2: ABI-2280 Vaginal Tablet, up to 1 mg or placebo tablet administered 3 times over a 1 week period.
Cohort B1 and B2 will be enrolled sequentially and enrollment into next higher dose cohort will not begin until key safety and PK data up to Day 9 from at least 6 participants in the cohort B1 become available. Additionally, all available cumulative safety and PK data from earlier cohorts in Part A and B will also be reviewed by the safety monitoring committee.
For Cohorts B1 and B2, participants may be admitted to the research unit on Days-1 and 4 and discharged on Days 2 and 6, respectively. Alternatively, they may be admitted to clinical research unit on Day-1 and discharged on Day 6. On Days 1 and 5 participants will receive the first and last doses and complete the procedures as detailed in schedule of assessment in the protocol.
Intervention code [1] 321785 0
Treatment: Drugs
Comparator / control treatment
Placebo Gel and Tablet
The placebo vaginal gel is comprised of carbopol 974, propylene glycol, ethylenediaminetetraacetic acid, disodium salt, sorbic acid, water and sodium hydroxide.
The placebo tablet is comprised of Mannito, magnesium stearate, and microcrystalline cellulose.
Control group
Placebo

Outcomes
Primary outcome [1] 329036 0
To assess the safety and tolerability of ABI-2280 Vaginal Gel and Tablet when administered as a single and multiple doses to the cervix of healthy adult women.
Safety and tolerability will be measured by:
1. The frequency and severity of Adverse events (AE); AEs will be assessed by Common terminology Criteria for Adverse Events (CtCAE4)
2. The relationship of adverse events to the study drug,
3. Safety laboratory tests (chemistry, hematology) from blood samples
4. Urinalysis from urine samples
5. vital signs, such as
a) body temperature assessed by the oral thermometer,
b) blood pressure measured by a sphygmomanometer,
c) heart rate assessed by ECG and manual 60 second count,
d) respiratory rate assessed by manual 60 count
6. physical abnormalities and
7. ECG- 12 lead ECG will be taken
Timepoint [1] 329036 0
Part A
AEs: Day 1 to day 8
Safety lab: Screening, Baseline, Day 2, 4 ,and 8
Vital signs: Screening, Baseline, Pre dose, 12 and 24 hour post dose, and Day 8
Part B (Cohorts B1-B2)
AEs: Day 1 to Day 15
Safety Lab: Screening, Baseline, 24 hours post dose (Day 2 & 6) Day 9 and Day 15
Vital signs: Screening, Baseline, Pre dose, 12 hours post dose (Day 1 and 5), 24 hours post dose (Day 2 & 6), Day 3, Day 9, and Day 15.
Secondary outcome [1] 401246 0
To determine the extent of systemic exposure to ABI-2280 Vaginal Gel and Tablet after single and multiple doses.
Pharmacokinetic parameters of ABI-2280 and its metabolite(s) including, but not limited to AUC0-last, AUC8, Cmax, tmax, and t1/2 will be calculated. For these assessments, blood samples will be taken at different time points.
Timepoint [1] 401246 0
Part A Pre dose, 1, 2, 4, 6, 8, 12, 24 hours post dose, Day4, and Day 8
Part B (Cohorts B1 and B2) Pre dose, 1, 2, 4, 6, 8, 12, 24, 48 hours post dose, Day 9 and Day 15

Eligibility
Key inclusion criteria
1. Women, 18 to 50 years old, with an intact uterus
2. Generally in good health with no clinically significant pulmonary, cardiac, gastroenterologic, neurologic, renal, musculoskeletal, rheumatologic, metabolic, neoplastic, or endocrine disease
3. Able and willing to use stringent methods of contraception from at least 1 month prior to the required abstinence period (up to Day 7) through to Day 28.
4. Agree to provide coital history at study visits, and any local adverse reactions for sexual partner
5. Agree to abstain from sexual activities such as oral sex or sexual intercourse, vaginal douching or insertion of any vaginal products other than the study drug for at least 48 hours prior to enrollment through 7 days after dosing
6. Generally regular menstrual cycles
7. Negative cervical screening test within 3 months of enrollment, and no history of cervical intraepithelial lesions at any time
8. Good physical and mental health on the basis of medical history, physical examination, clinical laboratory, ECG, and vital signs at screening and admission (day-1)
9. Willing and able to adhere to the study visit schedule, other protocol requirements, including pelvic examination and cervical image acquisition
Minimum age
18 Years
Maximum age
50 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Pregnant women, plan to become pregnant in next 3 months, lactating females
2. History of cancer, except basal cell or squamous cell carcinoma of the skin
3. History of genital herpes with more than 3 outbreaks per year
4. Have an active pelvic infection
5. Current or recent abnormal vaginal discharge and/or abnormal vaginal bleeding, abortion or miscarriage within the 3 months prior to randomization
6. Any clinically significant immune suppressing condition
7. Taking medications like inhaled or oral corticosteroids, systemic immunomodulatory treatments, over-the-counter intra-vaginal preparation or any prescription that in the opinion of investigator can interfere with the interpretation of the results
8. Hypersensitivity to any component of placebo formulation excipients or other nucleoside analogues (such as cidofovir, etc.)
9. Menses expected to start within 7 days of dosing for participants in Part A or 14 days for participants in Part B
10. Participants who test positive for HIV, Hepatitis B, or Hepatitis C at screening
11. Substance or alcohol abuse, history of anaphylaxis, or severe allergy to any food, drug or other exposure

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)
Sponsor or designee (e.g. CRO biostatistician) will prepare the study randomization schedule/treatment assignment by simple randomization and distribute to the unblinded site pharmacy team.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

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

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
13/11/2021
Actual
13/12/2021
Date of last participant enrolment
Anticipated
9/10/2022
Actual
Date of last data collection
Anticipated
31/10/2022
Actual
Sample size
Target
48
Accrual to date
5
Final
Recruitment in Australia
Recruitment state(s)
QLD,VIC
Recruitment hospital [1] 20577 0
Nucleus Network - Melbourne
Recruitment hospital [2] 21771 0
Q-Pharm Pty - Clive Berghofer Research Centre (CBCRC) - Herston
Recruitment hospital [3] 22434 0
Gold Coast University Hospital - Southport
Recruitment postcode(s) [1] 35364 0
3004 - Melbourne
Recruitment postcode(s) [2] 36825 0
4007 - Herston
Recruitment postcode(s) [3] 37635 0
4215 - Southport

Funding & Sponsors
Funding source category [1] 309744 0
Commercial sector/Industry
Name [1] 309744 0
Antiva Biosciences Inc.
Country [1] 309744 0
United States of America
Primary sponsor type
Commercial sector/Industry
Name
Antiva Biosciences Inc.
Address
280 Old County Road #257 Brisbane,
CA 94005, USA
Country
United States of America
Secondary sponsor category [1] 310765 0
None
Name [1] 310765 0
Address [1] 310765 0
Country [1] 310765 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309500 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 309500 0
Ethics committee country [1] 309500 0
Australia
Date submitted for ethics approval [1] 309500 0
06/10/2021
Approval date [1] 309500 0
03/11/2021
Ethics approval number [1] 309500 0

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

Contacts
Principal investigator
Name 114370 0
Dr Jason Lickliter
Address 114370 0
Level 5, Burnet Tower,
AMREP Precinct
89 Commercial Road
Melbourne, Victoria, 3004
Australia
Country 114370 0
Australia
Phone 114370 0
+61 3 9076 8960
Fax 114370 0
Email 114370 0
[email protected]
Contact person for public queries
Name 114371 0
Jonathan Lee
Address 114371 0
Antiva Biosciences Inc.
280 Old County Road, #257
Brisbane, CA 94005, USA
Country 114371 0
United States of America
Phone 114371 0
+1 650 822 1400
Fax 114371 0
Email 114371 0
[email protected]
Contact person for scientific queries
Name 114372 0
Jonathan Lee
Address 114372 0
Antiva Biosciences Inc.
280 Old County Road, #257
Brisbane, CA 94005, USA
Country 114372 0
United States of America
Phone 114372 0
+1 650 822 1400
Fax 114372 0
Email 114372 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.