Clinical trial NCT05555862: Artesunate Suppositories for the Treatment of HIV-negative Patients With Intra-anal HSIL
Official title: 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Anal High Grade Squamous Intraepithelial Lesion
Anal Precancerous Condition
AIN 2/3
HPV Infection
Anal Dysplasia
HPV Disease
Keywords: human papillomavirus
non-surgical
topical treatment
anal HSIL
anal cancer prevention
treatment study
cancer prevention
high-risk HPV
HPV16
suppository
Lead sponsor: Frantz Viral Therapeutics, LLC
Sponsor class: INDUSTRY
Collaborators: name: Amarex CRO
name: University of California, San Francisco
name: Anal Dysplasia Clinic MidWest
name: Laser Surgery Care
First posted: 2022-09-27
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Double blind, placebo controlled randomized trial
Primary purpose: TREATMENT

Brief summary: 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)

Detailed description: 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:

Efficacy:

* To evaluate the viral clearance after four 5-day cycles of artesunate suppositories in adults with biopsy-proven HPV-associated intra-anal anal HSIL over the study window (42 weeks)
* To evaluate complete and partial intra-anal histopathologic response after the week 18 time point but over the study window (30 weeks).
* To evaluate complete and partial peri-anal histopathologic response following artesunate suppositories over the course of the study (42 weeks).
* To evaluate persistence of response throughout the study window (42 weeks)

Safety:

To evaluate the safety of artesunate suppositories for the treatment of intra-anal HSIL.

Eligibility criteria: Inclusion Criteria:

* 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:

  1. Serum alanine transaminase (SGPT/ALT) \< 5 x upper limit of normal (ULN)
  2. Serum aspartate transaminase (SGOT/AST) \< 5 x ULN
  3. Serum Bilirubin (total) \< 2.5 x ULN
  4. Serum Creatinine ≤ 1.5 x ULN
* Electrocardiogram (ECG) with no clinically significant findings as assessed by the Investigator.
* Weight ≥ 50kg

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of subjects with complete and partial response by week 18
timeFrame: 18 weeks
Secondary outcomes:
measure: Number of participants who have achieved clearance of detectable human papilloma virus (HPV) over the study window
timeFrame: 42 weeks
measure: Number of participants with complete and partial response after week 18 but over the study window
timeFrame: 30 weeks
measure: 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
timeFrame: 42 weeks
measure: Number of participants who undergo complete response who maintain their response over the study window
timeFrame: 42 weeks
Other outcomes:
measure: Number of participants with Treatment-Emergent Adverse Events (TEAE)
timeFrame: 12 weeks
measure: Number of participants who withdrew from the study due to TEAEs
timeFrame: 12 weeks
measure: Changes in vital signs over the study window
timeFrame: 42 weeks
measure: Changes in physical examination abnormalities
timeFrame: 42 weeks
measure: Clinically significant changes in ECG between baseline and post dosing
timeFrame: 8 weeks
Locations:
city: Chicago
country: United States
facility: Anal Dysplasia Clinic MidWest
state: Illinois
city: New York
country: United States
facility: Laser Surgery Care
state: New York
Study officials:
affiliation: University of California, San Francisco
name: Joel Palefsky, MD
role: PRINCIPAL_INVESTIGATOR
References: