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Artesunate Pessaries for the Treatment of Human Papillomavirus and Cervical Precancer Among Women Living With HIV in Kenya
Trial Status: active
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.
Inclusion Criteria
Age 25 years or older
Known HIV seropositive status
On antiretroviral therapy for > 90 days prior to enrollment
Weight ≥ 50 kg at study entry
* Justification for weight criteria: A minimum body weight of 50 kg will meet the planned artesunate dosing of ≤ 4 mg/kg for which excellent safety data is available
Positive HPV screening test and within 4-8 weeks of thermal ablation
Ability to provide informed consent
Planning to stay within the study locale during the duration of the study (24 weeks)
Agreement to use contraception (barriers or hormonal) if of childbearing age through week 6 of the study
Exclusion Criteria
Current pregnancy or breastfeeding status
Current or past history of invasive cervical cancer
History of total hysterectomy
Currently receiving systemic chemotherapy or radiation therapy for another cancer
Current use of systemic immunosuppressants or steroids (> 10 mg of prednisone or equivalent)
Current use of efavirenz antiretroviral therapy, phenytoin, carbamazepine, and rifampin
Have a medical comorbidity that, in the opinion of the investigator, would interfere with study participation
Prior chemotherapy within 30 days prior to day 1 of study treatment
Male at birth
Additional locations may be listed on ClinicalTrials.gov for NCT06519994.
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.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationUNC Lineberger Comprehensive Cancer Center
