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

Study Overview
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Brief Summary
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This study evaluates the use of topical ABI-1968 cream, in the treatment of cervical precancerous lesions in adult women.

Official Title
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A Randomised, Double-Blind, Placebo-Controlled, Multiple-Dose Study to Evaluate Safety, Tolerability and Pharmacokinetics of Topical ABI-1968 in Subjects With Cervical High Grade Squamous Intreaepithelial Lesions (cHSIL)

Conditions
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HSIL, HSIL of Cervix, High-Grade Squamous Intraepithelial Lesions, High-grade Cervical Intraepithelial Neoplasia, Human Papilloma Virus, Cervical Cancer, Cervical Intraepithelial Neoplasia, Cervical Neoplasm, Cervical Dysplasia, CIN

Intervention / Treatment
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* Drug: ABI-1968


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women, 25 to 50 years old. Cervical HSIL diagnosis made within 2 months of enrollment and confirmed with biopsy with no evidence of invasive cancer in any specimen and must be p16+. Able and willing to abstain from sexual intercourse for 48 hours prior to first dose and 2 days after each dose. Generally experiencing regular menstrual cycles, unless using long-acting reversible contraception that induces amenorrhea (e.g., Mirena IUD, Norplant). Exclusion Criteria: Women who are pregnant, plan to become pregnant in the next 4 months, or lactating females. History of cancer, except basal cell or squamous cell carcinoma of the skin. History of genital herpes with > 3 outbreaks per year, or active non-HPV vaginal infection. Plan to have excision or ablation of the lesion(s) within 3 months of enrollment. History of cervical cancer, colposcopy suspicious for cancer, any prior treatment of CIN, or hysterectomy.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 50 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: Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Up to two ascending dose cohorts (8 subjects per cohort) may receive multiple doses in 2 ascending dose strengths of ABI-1968 Topical Cream. After completing the multiple ascending dose portion a Cohort Expansion group of 32 to 40 subjects will be initiated.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose 1 - Multiple Ascending Dose (MAD)<br>ABI-1968 or Placebo topical cream applied at Day 1, Day 8, Day 15 and Day 22 | Drug: ABI-1968<br>* Topical ABI-1968 Cream or Placebo with 4 doses administered up to 4 Cohorts<br>|
| Experimental: Dose 2 - Multiple Ascending Dose (MAD)<br>ABI-1968 or Placebo topical cream applied at Day 1, Day 8, Day 15 and Day 22 | Drug: ABI-1968<br>* Topical ABI-1968 Cream or Placebo with 4 doses administered up to 4 Cohorts<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 cHSIL | Number of participants with Adverse Events related to treatment to determine MTD | 85 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systemic exposure to Topical ABI-1968 Cream following topical application to the cervix. | Plasma concentrations of ABI-1968 over time to determine systemic exposure | 85 Days | 
| Histopathology of areas with biopsy-proven disease following multiple doses of Topical ABI-1968 Cream. | Number of subjects with complete and or partial regression of cHSIL by Colposcopy and histopathology to determine change and impact over 4 weekly doses | 85 Days |