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

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)

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.

Study Overview

• Status: Completed
• Conditions: HIV Infection; Anal Cancer; Anus Neoplasms; Human Papilloma Virus Infection; HSIL, High-Grade Squamous Intraepithelial Lesions
• Intervention / Treatment: Drug: ABI-1968

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Darlinghurst
    • Sydney, Darlinghurst, Australia, 2010
      • Research Center
• United States
  • California
    • San Francisco, California, United States, 94115
      • Research Center
  • Florida
    • Orlando, Florida, United States, 32803
      • Research Center
  • Illinois
    • Chicago, Illinois, United States, 60614
      • Research Center
  • New York
    • New York, New York, United States, 10011
      • Research Center
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Female or male subjects, at least 27 years old.
2. Confirmed diagnosis of intra-anal HSIL at least 3 months prior to screening and confirmed by histopathology (with p16 positive staining)
3. Intra-anal HSIL are visible and evaluable by HRA at the time of screening, and no lesion(s) is suspicious for invasive cancer.
4. 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:

1. Women who are pregnant, plan to become pregnant in the next 3 months, or lactating females.
2. Received topical treatment or ablative procedures for aHSIL in the 6 months prior to enrolment.
3. 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.
4. History of genital herpes with > 3 outbreaks per year.
5. Plan to have excision or ablation of the lesion(s) within 3 months of enrolment.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

10

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Antiva Biosciences
• Investigators: Study Chair: Clinical Operations, Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may use the contacts provided below.

Study record dates

Study Major Dates

• Study Start (Actual): August 11, 2017
• Primary Completion (Actual): February 4, 2019
• Study Completion (Actual): February 4, 2019

Study Registration Dates

• First Submitted: June 24, 2017
• First Submitted That Met QC Criteria: June 27, 2017
• First Posted (Actual): June 29, 2017

Study Record Updates

• Last Update Posted (Actual): February 7, 2019
• Last Update Submitted That Met QC Criteria: February 5, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Virus Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Uterine Cervical Diseases; Uterine Diseases; Disease Attributes; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; DNA Virus Infections; Intestinal Neoplasms; Rectal Diseases; Tumor Virus Infections; Colorectal Neoplasms; Precancerous Conditions; Neoplasms, Squamous Cell; Rectal Neoplasms; Anus Diseases; Uterine Cervical Dysplasia; Carcinoma in Situ; Infections; Communicable Diseases; Carcinoma, Squamous Cell; Anus Neoplasms; Papillomavirus Infections; Papilloma; Squamous Intraepithelial Lesions of the Cervix
• Other Study ID Numbers: ABI-1968-201

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