This phase II trial tests whether artesunate pessaries (vaginal inserts) can improve the treatment of human papillomavirus (HPV) and cervical precancer after thermal ablation (a procedure using heat to remove tissue or a part of the body, or destroy its function) in women living with HIV (WLWH) in Kenya. WLWH face up to six times increased risk of cervical cancer. Infection with HPV can lead to precancerous changes in the cervix that, if not adequately treated, can progress to cancer. Current treatments for HPV or cervical precancer in WLWH, including thermal ablation, are associated with high rates of treatment failure. Artesunate is a drug extracted from artemisia annua plant with anti-malarial activity. It may also prevent viral growth. Giving artesunate pessaries may be effective in treating HPV and cervical precancer after thermal ablation in WLWH in Kenya.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT06519994.
PRIMARY OBJECTIVE:
I. To estimate type-specific HPV clearance rates at 24 weeks among women living with HIV (WLWH) randomized to adjuvant self-administered artesunate vaginal inserts versus (vs.) placebo inserts following thermal ablation in Kenya.
SECONDARY OBJECTIVES:
I. To evaluate the safety of adjuvant artesunate vaginal inserts vs placebo following thermal ablation among WLWH.
II. To evaluate adherence, defined as the use of at least 80% (12 of 15) self-administered artesunate or placebo vaginal inserts following thermal ablation in WLWH.
III. To investigate the acceptability of artesunate vs. placebo vaginal inserts as adjuvant therapy following thermal ablation in WLWH.
IV. To evaluate study uptake, accrual, and retention rates through week 24.
EXPLORATORY OBJECTIVES:
I. To investigate longitudinal changes in the cervicovaginal microbiome (CVM) following intravaginal artesunate pessary vs. placebo use among WLWH.
II. To investigate the frequency and magnitude of genital HIV-1 shedding and measures of local immune activation following intravaginal artesunate pessary vs. placebo use among WLWH.
III. To investigate changes in HPV methylation markers between placebo and control arms.
IV. To investigate the impact of the male microbiome on HPV clearance by treatment arm.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive artesunate pessaries self-administered vaginally once a night (QPM) for 5 days on weeks 1, 3, and 5. Patients undergo pelvic examination, colposcopy, blood sample collection, and cervicovaginal swab and lavage sample collection throughout the study.
ARM II: Patients receive placebo pessaries self-administered vaginally QPM for 5 days on weeks 1, 3, and 5. Patients undergo pelvic examination, colposcopy, blood sample collection, and cervicovaginal swab and lavage sample collection throughout the study.
After completion of study treatment, patients are followed up at 12 and 24 weeks.
Lead OrganizationUNC Lineberger Comprehensive Cancer Center
Principal InvestigatorChemtai Mungo
