A Study of ABI-2280 Vaginal Tablet in Participants With Cervical Intraepithelial Neoplasia

An Open-Label Single and Multiple-dose, Study to Evaluate Safety, Tolerability and Efficacy of ABI-2280 Vaginal Tablet in Participants With Cervical Squamous Intraepithelial Lesions

This is an open-label study to evaluate the safety, tolerability, and efficacy of ABI-2280 in participants with cervical squamous intraepithelial lesions. This study is divided into 2 parts - Part A and Part B.

Part A consists of 3 dose escalating cohorts. Part B is a dose expansion cohort.

Participants will self-administer ABI-2280.

Study Overview

• Status: Recruiting
• Conditions: Cervical Intraepithelial Neoplasia
• Intervention / Treatment: Drug: ABI-2280

• Study Type: Interventional
• Enrollment (Estimated): 29
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Oranee Daniels, MD; Phone Number: 650-822-1400; Email: odaniels@antivabio.com

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Recruiting
      • East Sydney Doctors
      • Contact: Heather Farlow; Email: hfarlow@eastsydneydoctors.com.au
  • Queensland
    • Southport, Queensland, Australia, 4215
      • Not yet recruiting
      • Gold Coast University Hospital
      • Contact: Danielle Miller; Email: danielle.miller@health.qld.gov.au
• South Africa
  • Free State
    • Bloemfontein, Free State, South Africa, 9301
      • Recruiting
      • Farmvos
      • Contact: Reinard McPherson, MD; Phone Number: 27835262564; Email: reinard.mcpherson@farmvos.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women, 25 to 55 years old.
• For Part A, 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.
• For Part B, biopsy-confirmed cervical HSIL that is p16+ (p16INK4a expressed) within 60 days of enrollment (dosing) with no evidence of invasive cancer in any specimen. If biopsy was performed more than 60 days before planned enrollment, participants must agree to have another biopsy performed at the Screening visit, unless approved by the Medical Monitor.
• No prior treatment for Cervical intraepithelial neoplasia (CIN).
• Generally, in good health with no clinically significant pulmonary, cardiac, gastro-enterologic, neurologic, renal, musculoskeletal, rheumatologic, metabolic, neoplastic, or endocrine disease.

Exclusion Criteria:

• Women who are pregnant, plan to become pregnant in the next 4 months, or lactating females.
• Unwilling to use stringent methods of contraception (including barrier method, as well as another acceptable method) throughout the course of the study.
• History of cancer, except basal cell or squamous cell carcinoma of the skin.
• History of genital herpes with outbreak within prior 12 months.
• 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).
• Current or recent abnormal vaginal discharge and /or abnormal vaginal bleeding.
• Had a therapeutic abortion or miscarriage less than 3 months prior.
• Any clinically significant immune suppressing condition.
• 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.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ABI-2280 0.1mg; 0.1mg vaginal tablet	Drug: ABI-2280; Vaginal Tablet
Experimental: ABI-2280 0.3mg; 0.3mg vaginal tablet	Drug: ABI-2280; Vaginal Tablet
Experimental: ABI-2280 1.0mg; 1.0mg vaginal tablet	Drug: ABI-2280; Vaginal Tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (Safety and Tolerability)	For Parts A and B, to assess the safety and tolerability of ABI-2280 Vaginal Tablet by the incidence and severity of Adverse events (AEs).	From Baseline to Day 42 post dose administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetics of ABI-2280 after single and multiple doses	Time to maximum observed drug concentration (tmax)	60 minutes prior to dosing on Day 1, and 1 hour (± 5 mins) and 6 hours (± 1 hour) post-dose on Day 1. For Part A, additional samples will be taken at 2 hours (± 5 mins) and 24 hours (± 2 hours) post dose on Day 1.
Pharmacokinetics of ABI-2280 after single and multiple doses	Maximum observed drug concentration (Cmax)	60 minutes prior to dosing on Day 1, and 1 hour (± 5 mins) and 6 hours (± 1 hour) post-dose on Day 1. For Part A, additional samples will be taken at 2 hours (± 5 mins) and 24 hours (± 2 hours) post dose on Day 1.
Pharmacokinetics of ABI-2280 after single and multiple doses	Area under the curve (AUC) from time zero to last measurable concentration (AUC0-last)	60 minutes prior to dosing on Day 1, and 1 hour (± 5 mins) and 6 hours (± 1 hour) post-dose on Day 1. For Part A, additional samples will be taken at 2 hours (± 5 mins) and 24 hours (± 2 hours) post dose on Day 1.
Pharmacokinetics of ABI-2280 after single and multiple doses	AUC from time zero to infinity (AUC8)	60 minutes prior to dosing on Day 1, and 1 hour (± 5 mins) and 6 hours (± 1 hour) post-dose on Day 1. For Part A, additional samples will be taken at 2 hours (± 5 mins) and 24 hours (± 2 hours) post dose on Day 1.
Pharmacokinetics of ABI-2280 after single and multiple doses	Apparent elimination half-life (t½)	60 minutes prior to dosing on Day 1, and 1 hour (± 5 mins) and 6 hours (± 1 hour) post-dose on Day 1. For Part A, additional samples will be taken at 2 hours (± 5 mins) and 24 hours (± 2 hours) post dose on Day 1.
Pharmacokinetics of ABI-2280 after single and multiple doses	Apparent terminal elimination rate constant (Kel)	60 minutes prior to dosing on Day 1, and 1 hour (± 5 mins) and 6 hours (± 1 hour) post-dose on Day 1. For Part A, additional samples will be taken at 2 hours (± 5 mins) and 24 hours (± 2 hours) post dose on Day 1.
Pharmacokinetics of ABI-2280 after single and multiple doses	Apparent clearance (CL/F)	60 minutes prior to dosing on Day 1, and 1 hour (± 5 mins) and 6 hours (± 1 hour) post-dose on Day 1. For Part A, additional samples will be taken at 2 hours (± 5 mins) and 24 hours (± 2 hours) post dose on Day 1.
Pharmacokinetics of ABI-2280 after single and multiple doses	Apparent volume of distribution at the terminal phase (Vz/F)	60 minutes prior to dosing on Day 1, and 1 hour (± 5 mins) and 6 hours (± 1 hour) post-dose on Day 1. For Part A, additional samples will be taken at 2 hours (± 5 mins) and 24 hours (± 2 hours) post dose on Day 1.
Histopathologic changes in cHSIL by large loop excision of the transformation zone (LLETZ) specimen	To assess histopathologic changes in cHSIL by LLETZ	12 weeks after the first dose of ABI-2280 Vaginal Tablet

Collaborators and Investigators

• Sponsor: Antiva Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2022
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): May 31, 2024

Study Registration Dates

• First Submitted: August 7, 2022
• First Submitted That Met QC Criteria: August 12, 2022
• First Posted (Actual): August 16, 2022

Study Record Updates

• Last Update Posted (Actual): July 6, 2023
• Last Update Submitted That Met QC Criteria: July 4, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Carcinoma; Neoplasms, Glandular and Epithelial; Uterine Cervical Diseases; Uterine Diseases; Precancerous Conditions; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Neoplasms; Carcinoma in Situ; Uterine Cervical Dysplasia
• Other Study ID Numbers: ABI-2280-303

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No