Feasibility of Intravaginal Artesunate as Adjuvant HPV & Cervical Precancer Treatment in Kenya

UNC Lineberger Comprehensive Cancer Center

Status and phase: Active, not recruiting; Phase 2

Conditions: Human Immunodeficiency Virus; Cervical Precancer; Human Papillomavirus

Treatments: Drug: Artesunate vaginal inserts; Drug: Placebo vaginal inserts

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06519994

LCCC2330

R34CA284983 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The objective of this randomized, placebo-controlled trial is to evaluate whether intravaginal artesunate pessaries (vaginal inserts) can be used as adjuvant therapy following thermal ablation to improve Human papillomavirus (HPV) treatment outcomes in Women Living with Human Immunodeficiency Virus (WLWH).

The study will evaluate whether women who use artesunate will have higher HPV clearance at 6 months, compared to those who used a placebo. The study will also assess the safety, adherence, and acceptability of this treatment. 120 participants will be enrolled in the study. Participants will self-administer the study drug nightly for 5 days, take a week off, and repeat twice (use study drug on weeks 1, 3,5) and will return to the clinic on weeks 2, 4, 6, 12, and week 24 for follow-up.

Full description

WLWH face up to six times increased risk of cervical cancer, as a result, cervical cancer is a leading cause of death in this population. Cervical cancer is caused by persistent infection with the human papillomavirus (HPV), resulting in precancerous changes that if not adequately treated, progress to cancer. Thermal ablation is a commonly used treatment for cervical precancer in Kenya and other low- and middle-income countries (LMICs). Current treatments for HPV or cervical precancer, including thermal ablation, are associated with high rates of treatment failure in WLWH. In a recent study from Zambia, only 44% of WLWH had cleared HPV at six months following thermal ablation treatment. Other studies have demonstrated up to 30% recurrence rate of high-grade cervical precancer at 12 to 24 months after treatment. Persistent infection with HPV following precancer treatment is a key risk factor for treatment disease recurrence.

Enrollment: 120 patients

Sex: Female

Ages: 25+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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*
• 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 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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120 participants in 2 patient groups, including a placebo group

Artesunate vaginal inserts

Experimental group

Description:

Participants will self-administer the study drug nightly for 5 days, take a week off, and repeat 2 times (study drug application on weeks 1, 3, 5).

Treatment:

Drug: Artesunate vaginal inserts

Placebo vaginal inserts

Placebo Comparator group

Description:

Participants will self-administer the study placebo nightly for 5 days, take a week off, and repeat 2 times (study drug application on weeks 1, 3, 5).

Treatment:

Drug: Placebo vaginal inserts