A Phase II Double Blind, Placebo-controlled, Randomized Trial of Artesunate Suppositories for the Treatment of HIV-negative Patients With Anal High-grade Squamous Intraepithelial Lesions (Anal HSIL)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 17
- 试验地点
- 2
- 主要终点
- Number of subjects with complete and partial response by week 18
研究概览
简要总结
This is a phase II double blind, placebo-controlled, randomized study of Artesunate suppositories for the treatment of HIV-negative men and women who have anal high grade squamous intraepithelial lesions (anal HSIL)
详细描述
Eligible participants in this study are randomized 2:1 to receive either artesunate or placebo suppositories for the treatment of anal HSIL. Both groups receive four 5-day cycles of suppositories, at weeks 0, 2, 4, and 6. At least two of the dosing visits are done in person. The remaining dosing visits may be done as telehealth visits (suppositories are mailed to the patient's home). Participants are followed closely with anoscopy or high resolution anoscopy (HRA) at weeks 8, 18, 30, and 42. After the week 18 HRA visit, participants who have at least partial response will be followed with HRA at week 30.
Participants who are found to be non-responders at week 18 will undergo standard of care ablation.
Participants who are found to have anal HSIL at weeks 30 or 42 will be followed according to standard of care procedures.
Primary Objective: To evaluate the complete and partial histopathologic response to four 5-day cycles of artesunate suppositories in adult patients with biopsy-proven HPV-associated intra-anal HSIL (18 weeks).
Secondary Objectives:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Double-blind, placebo-controlled
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult men and women age ≥ 18 years
- •Capable of informed consent
- •Biopsy-confirmed intra-anal high-grade dysplasia (AIN 2, AIN 3, anal HSIL) by HRA. Patients must have residual anal HSIL lesions after diagnostic biopsies, as documented by HRA. This includes patients who are newly diagnosed with anal HSIL as well as those who have recurrent anal HSIL after medical therapy or surgical therapy. Patients who have intra-anal HSIL and also have peri-anal HSIL may be enrolled in the study.
- •Women of childbearing potential agree to use birth control for the duration of the study.
- •Laboratory values at Screening of:
- •Serum alanine transaminase (SGPT/ALT) < 5 x upper limit of normal (ULN)
- •Serum aspartate transaminase (SGOT/AST) < 5 x ULN
- •Serum Bilirubin (total) < 2.5 x ULN
- •Serum Creatinine ≤ 1.5 x ULN
- •Electrocardiogram (ECG) with no clinically significant findings as assessed by the Investigator.
- •Weight ≥ 50kg
排除标准
- •Pregnant and nursing women
- •Diagnosis of low-grade anal dysplasia (AIN 1, LSIL), without the concomitant diagnosis of anal HSIL, by HRA
- •Concurrent anal, vulvar, cervical, or penile cancer
- •HIV seropositivity
- •Currently receiving systemic chemotherapy or radiation therapy for another cancer.
- •Patients who are on medical treatment with systemic immunosuppressants or steroids (e.g., active autoimmune disease)
- •Concomitant use of strong Uridine glucuronyl transferases (UGT) inhibitors
- •Concomitant use of imiquimod or 5-fluorouracil (5-FU) for the duration of the study
研究组 & 干预措施
Artesunate suppositories
Four 5-day cycles of artesunate suppositories
干预措施: Artesunate (Drug)
Placebo suppositories
Four 5-day cycles of placebo suppositories
干预措施: Placebo (Drug)
结局指标
主要结局
Number of subjects with complete and partial response by week 18
时间窗: 18 weeks
Number of participants who achieve complete or partial response after 4 5-day cycles of artesunate as determined by HRA-directed biopsy(ies)
次要结局
- Number of participants who have achieved clearance of detectable human papilloma virus (HPV) over the study window(42 weeks)
- Number of participants with complete and partial response after week 18 but over the study window(30 weeks)
- Number of participants who achieve complete and partial response of peri-anal HSIL, following 4 cycles of intra-anal artesunate suppositories, as determined by HRA-directed biopsy(42 weeks)
- Number of participants who undergo complete response who maintain their response over the study window(42 weeks)