Human Papillomavirus (HPV) is a common virus that can affect both men and women. There are several types of HPV, with some considered high-risk for causing cancers, particularly cervical cancer in women. High-risk HPV (hrHPV) infections are a global health concern. These infections are often spread through intimate contact and can persist for years without causing symptoms. In some cases, however, hrHPV infections can lead to the development of cancers, including cervical cancers. Globally, hrHPV is a widespread issue. It is estimated that over 80% of sexually active individuals may acquire an HPV infection at some point in their lives. Cervical cancer, primarily caused by hrHPV, is a leading cause of cancer-related deaths among women in many parts of the world, particularly in low- and middle-income countries where access to screening and preventive measures is limited. There are currently no treatments options for persistent hrHPV, and women are essentially asked to “wait and see” if their hrHPV infections resolve, persist, or progress to pre-cancer or cancer of the cervix. A topical treatment that is safe and effective in clearing persistent hrHPV would be beneficial in not only preventing progression of infection to pre-cancer and cervical cancer, but also in reducing potential transmission of the virus. The study drug, ABI-2280 is an experimental drug, developed to treat persistent hrHPV infection. The purpose of this study is to identify the effect, good or bad of ABI-2280 while identifying the highest tolerated dose. This will be compared against placebo to tell how well ABI-2280 works against hrHPV. Placebo is an inactive substance that contains no active ingredient but looks like the study drug. A total of 160 participants will be enrolled globally across 5 countries. Participants will be allocated by chance to receive ABI-2280 (3 out of 4 chance) or placebo (1 out of 4 chance) and assigned to one of up to 11 treatment groups where different doses may be evaluated. Subject participation will involve a combination of visits to the clinic and wellness visits (contact by telephone, email, or text) over approximately 30 weeks total and a final follow-up visit at Week 52 (about one year after the first dose). Some of the risks of participating in the study include mild to severe side effects of the study drug. These will be closely monitored by the study team. Although the study drug may or may not benefit the participants, information learned may help guide the treatment of other patients with persistent hrHPV infection. The results of the study will be shared openly and information on the trial provided to healthcare professionals and to the public, at scientific congresses, in clinical trial registries, and in peer-reviewed journals. The results will also be shared with the study participants.

Human papillomavirus (HPV) infection is the most common sexually transmitted infection (STI), and it is estimated that ~85% of all women will be infected during their lifetime. While most HPV infections are transient and clear within a couple of years, persistent hrHPV types are associated with 95% of cervical cancer cases, with genotypes 16 and 18 being the most common. Worldwide, the overall burden of cervical cancer and related deaths ranks fourth among all cancers for women. In Sub-Saharan Africa, cervical cancer continues to be a significant health burden. In 2023, estimates show up to 5236 new cases of cervical cancer in Kenya. Over 60% of the cases were related to HPV 16 and 18. Anecdotal evidence suggests that the burden cuts across the country and is more pronounced in rural Kenya; western Kenya included; where resources are more scarce. Current management guidelines call for expectant management and re-testing in 12 months for hrHPV-positive (hrHPV+) women without evidence of high-grade cervical dysplasia (i.e., CIN2/3) or malignancy. This means women are essentially asked to “wait and see” if their hrHPV infections resolve, persist, or progress to pre-cancer or cancer of the cervix.

The study drug, ABI-2280, is a pro-drug of a potent human DNA polymerase inhibitor, for topical intravaginal treatment of several precancerous and potentially precancerous conditions related to human papillomavirus (HPV) infection, including persistent hrHPV infection in women. This Phase 1b/2 placebo-controlled global, multicenter study will primarily evaluate the safety and tolerability of various doses and dosing regimens of ABI-2280 Vaginal Insert vs. placebo. A total of 160 patients will be enrolled globally.

The primary endpoint in the sentinel cohorts (first 8 subjects of each cohort) will be the incidence and severity of adverse events (AEs), relationship of AEs to investigational product (IP), and AEs leading to treatment reduction/discontinuation for ABI-2280 Vaginal Insert vs. pooled placebo. The primary endpoint of the full expanded cohorts (i.e., all 40 subjects in the cohort) will be to evaluate clearance of the hrHPV infection at Week 12. As there are currently, no approved treatments for hrHPV infections, findings from this study will be key in providing an option for treating persistent hrHPV infection before progression to the pre-cancerous stage and ultimately to cervical cancer.