Study of Topical ABI-1968 in Subjects With Precancerous Anal Lesions Resulting From Human Papillomavirus (HPV) Infection

Study Overview
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Brief Summary
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This study evaluates the use of ABI-1968, a topical cream, in the treatment of anal precancerous lesions in adults with and without human immunodeficiency virus (HIV) infection.

Official Title
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Open-Label Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of Single and Multiple Doses of Topical ABI-1968 in Subjects With Anal High-Grade Squamous Intraepithelial Lesions (aHSIL)

Conditions
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Anus Neoplasms, HSIL, High-Grade Squamous Intraepithelial Lesions, Human Papilloma Virus Infection, HIV Infection, Anal Cancer

Intervention / Treatment
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* Drug: ABI-1968


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female or male subjects, at least 27 years old. Confirmed diagnosis of intra-anal HSIL at least 3 months prior to screening and confirmed by histopathology (with p16 positive staining) Intra-anal HSIL are visible and evaluable by HRA at the time of screening, and no lesion(s) is suspicious for invasive cancer. For HIV-positive subjects, CD4 count must be at least 200/mm3 with undetectable (<50 copies/mL) viral load within the 3 months prior to enrollment. Subjects must be on a stable regimen of antiretroviral drugs for the 3 months prior to enrollment. Exclusion Criteria: Women who are pregnant, plan to become pregnant in the next 3 months, or lactating females. Received topical treatment or ablative procedures for aHSIL in the 6 months prior to enrolment. History of cancer, including anal cancer (with the exception of basal cell or squamous cell carcinoma of the skin), or currently undergoing treatment for any skin cancer. History of genital herpes with > 3 outbreaks per year. Plan to have excision or ablation of the lesion(s) within 3 months of enrolment.

Ages Eligible for Study
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Minimum Age: 27 Years

Sexes Eligible for Study
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All

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: Sequential Assignment
Interventional Model Description: The study will be conducted in 2 Phases: Part A, up to 5 cohorts of 3 subjects each will receive a single dose of ABI-1968 Topical Cream. In Part B, three cohorts (3 subjects per cohort) will receive multiple doses in 3 ascending dose strengths of ABI-1968 Topical Cream. After completing the ascending dose multiple-dosing cohorts, a multiple-dosing Cohort Expansion group of 30 subjects will be initiated.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose 1 -Single Ascending Dose (SAD)<br>SAD Dose Level 1 of ABI-1968 topical cream applied on Day 1 of the study | Drug: ABI-1968<br>* Topical cream applied at Day 1 for the SAD portion and applied at Day 1, Day 8, Day 15, Day 22 and Day 29 for the MAD portion<br>|
| Experimental: Dose 2 -Single Ascending Dose (SAD)<br>SAD Dose Level 2 of ABI-1968 topical cream applied on Day 1 of the study | Drug: ABI-1968<br>* Topical cream applied at Day 1 for the SAD portion and applied at Day 1, Day 8, Day 15, Day 22 and Day 29 for the MAD portion<br>|
| Experimental: Dose 3 -Single Ascending Dose(SAD)<br>SAD Dose Level 3 of ABI-1968 topical cream applied on Day 1 of the study | Drug: ABI-1968<br>* Topical cream applied at Day 1 for the SAD portion and applied at Day 1, Day 8, Day 15, Day 22 and Day 29 for the MAD portion<br>|
| Experimental: Dose 4 -Single Ascending Dose(SAD)<br>SAD Dose Level 4 of ABI-1968 topical cream applied on Day 1 of the study | Drug: ABI-1968<br>* Topical cream applied at Day 1 for the SAD portion and applied at Day 1, Day 8, Day 15, Day 22 and Day 29 for the MAD portion<br>|
| Experimental: Dose 5 -Single Ascending Dose(SAD)<br>SAD Dose Level 5 of ABI-1968 topical cream applied on Day 1 of the study | Drug: ABI-1968<br>* Topical cream applied at Day 1 for the SAD portion and applied at Day 1, Day 8, Day 15, Day 22 and Day 29 for the MAD portion<br>|
| Experimental: Dose 1 - Multiple Ascending Dose(MAD)<br>MAD Dose Level 1 of ABI-1968 topical cream applied at Day 1, Day 8, Day 15, Day 22 and Day 29 | Drug: ABI-1968<br>* Topical cream applied at Day 1 for the SAD portion and applied at Day 1, Day 8, Day 15, Day 22 and Day 29 for the MAD portion<br>|
| Experimental: Dose 2 -Multiple Ascending Dose(MAD)<br>MAD Dose Level 2 of ABI-1968 topical cream applied at Day 1, Day 8, Day 15, Day 22 and Day 29 | Drug: ABI-1968<br>* Topical cream applied at Day 1 for the SAD portion and applied at Day 1, Day 8, Day 15, Day 22 and Day 29 for the MAD portion<br>|
| Experimental: Dose 3 -Multiple Ascending Dose(MAD)<br>MAD Dose Level 3 of ABI-1968 topical cream applied at Day 1, Day 8, Day 15, Day 22 and Day 29 | Drug: ABI-1968<br>* Topical cream applied at Day 1 for the SAD portion and applied at Day 1, Day 8, Day 15, Day 22 and Day 29 for the MAD portion<br>|
| Experimental: Multiple Ascending Dose (MAD) Cohort Expansion<br>MAD Cohort Expansion of ABI-1968 applied at Day 1, Day 8, Day 15, Day 22 and Day 29 | Drug: ABI-1968<br>* Topical cream applied at Day 1 for the SAD portion and applied at Day 1, Day 8, Day 15, Day 22 and Day 29 for the MAD portion<br>|
| Experimental: Dose 4-Multiple Ascending Dose(MAD)<br>MAD Dose Level 3 of ABI-1968 topical cream applied at Day 1, Day 8, Day 15, Day 22 and Day 29 | Drug: ABI-1968<br>* Topical cream applied at Day 1 for the SAD portion and applied at Day 1, Day 8, Day 15, Day 22 and Day 29 for the MAD portion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose (MTD) of ABI-1968 for the treatment of aHSIL | Number of participants with Adverse Events related to treatment | SAD portion is 29 days/MAD portion is 84 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systemic exposure to ABI-1968 Topical Cream following topical application to the anal canal. | Plasma concentrations of ABI-1968 over time | SAD portion is 29 days/MAD portion is 84 days | 
| Histopathology of areas with biopsy-proven disease following single and multiple doses of ABI-1968 Topical Cream. | Number of subjects with complete and or partial regression of aHSIL by High Resolution Anoscopy (HRA) and histopathology | SAD portion is 29 days/MAD portion is 84 days |