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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Cervical Intraepithelial Neoplasia

Intervention / Treatment
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* Drug: ABI-2280


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABI-2280 0.1mg<br>0.1mg vaginal tablet | Drug: ABI-2280<br>* Vaginal Tablet<br>|
| Experimental: ABI-2280 0.3mg<br>0.3mg vaginal tablet | Drug: ABI-2280<br>* Vaginal Tablet<br>|
| Experimental: ABI-2280 1.0mg<br>1.0mg vaginal tablet | Drug: ABI-2280<br>* Vaginal Tablet<br>|

What is the study measuring?
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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 |