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Artesunate Suppositories for the Treatment of HIV-negative Patients With Intra-anal HSIL (anal HSIL HIV-)

Primary Purpose

Anal High Grade Squamous Intraepithelial Lesion, Anal Precancerous Condition, AIN 2/3

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Artesunate

Placebo

About this trial

This is an interventional treatment trial for Anal High Grade Squamous Intraepithelial Lesion focused on measuring human papillomavirus, non-surgical, topical treatment, anal HSIL, anal cancer prevention, treatment study, cancer prevention, high-risk HPV, HPV16, suppository

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Anal Neoplasia and Cancer Research and Education Center
Anal Dysplasia Clinic MidWestRecruiting
Laser Surgery CareRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Artesunate suppositories

Placebo suppositories

Arm Description

Four 5-day cycles of artesunate suppositories

Four 5-day cycles of placebo suppositories

Outcomes

Primary Outcome Measures

Number of subjects with complete and partial response by week 18

Number of participants who achieve complete or partial response after 4 5-day cycles of artesunate as determined by HRA-directed biopsy(ies)

Secondary Outcome Measures

Number of participants who have achieved clearance of detectable human papilloma virus (HPV) over the study window

Number of participants who had HPV strains detected at study entry which become undetectable within the study window

Number of participants with complete and partial response after week 18 but over the study window

Number of participants who achieve complete or partial response after week 18, as documented by HRA-directed biopsy(ies)

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

Number of participants who had both peri-anal and intra-anal HSIL, whose peri-anal HSIL achieves complete or partial response following 4 cycles of intra-anal artesunate suppositories

Number of participants who undergo complete response who maintain their response over the study window

Number of participants who complete or partial response who maintain this response over the study window

Full Information

NCT ID

NCT05555862

First Posted

September 22, 2022

Last Updated

September 7, 2023

Sponsor

Frantz Viral Therapeutics, LLC

Collaborators

Amarex CRO, University of California, San Francisco, Anal Dysplasia Clinic MidWest, Laser Surgery Care

1. Study Identification

Unique Protocol Identification Number

NCT05555862

Brief Title

Artesunate Suppositories for the Treatment of HIV-negative Patients With Intra-anal HSIL

Acronym

anal HSIL HIV-

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

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Recruiting

Study Start Date

February 10, 2023 (Actual)

Primary Completion Date

February 28, 2024 (Anticipated)

Study Completion Date

August 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Frantz Viral Therapeutics, LLC

Collaborators

Amarex CRO, University of California, San Francisco, Anal Dysplasia Clinic MidWest, Laser Surgery Care

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Double blind, placebo controlled randomized trial

Masking

ParticipantInvestigator

Masking Description

Double-blind, placebo-controlled

Allocation

Randomized

Enrollment

48 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Artesunate suppositories

Arm Type

Experimental

Arm Description

Four 5-day cycles of artesunate suppositories

Arm Title

Placebo suppositories

Arm Type

Placebo Comparator

Arm Description

Four 5-day cycles of placebo suppositories

Intervention Type

Drug

Intervention Name(s)

Artesunate

Other Intervention Name(s)

Artesunic acid, dihydroartemisinin (DHA), artemisinin

Intervention Description

artesunate formulated as intra-anal suppositories

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

placebo intra-anal suppository

Primary Outcome Measure Information:

Title

Number of subjects with complete and partial response by week 18

Description

Number of participants who achieve complete or partial response after 4 5-day cycles of artesunate as determined by HRA-directed biopsy(ies)

Time Frame

18 weeks

Secondary Outcome Measure Information:

Title

Number of participants who have achieved clearance of detectable human papilloma virus (HPV) over the study window

Description

Number of participants who had HPV strains detected at study entry which become undetectable within the study window

Time Frame

42 weeks

Title

Number of participants with complete and partial response after week 18 but over the study window

Description

Number of participants who achieve complete or partial response after week 18, as documented by HRA-directed biopsy(ies)

Time Frame

30 weeks

Title

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

Description

Number of participants who had both peri-anal and intra-anal HSIL, whose peri-anal HSIL achieves complete or partial response following 4 cycles of intra-anal artesunate suppositories

Time Frame

42 weeks

Title

Number of participants who undergo complete response who maintain their response over the study window

Description

Number of participants who complete or partial response who maintain this response over the study window

Time Frame

42 weeks

Other Pre-specified Outcome Measures:

Title

Number of participants with Treatment-Emergent Adverse Events (TEAE)

Description

Number of participants who had adverse events, as defined by CTCAE v5.0, related to the study intervention

Time Frame

12 weeks

Title

Number of participants who withdrew from the study due to TEAEs

Description

Number of participants who were withdrawn from the study due to adverse events related to the study drug

Time Frame

12 weeks

Title

Changes in vital signs over the study window

Description

Number of participants who had clinically significant changes in vital signs

Time Frame

42 weeks

Title

Changes in physical examination abnormalities

Description

Number of participants who had clinically significant changes in physical examination abnormalities

Time Frame

42 weeks

Title

Clinically significant changes in ECG between baseline and post dosing

Description

Number of participants who had clinical significant changes in ECG between pre-dosing and post dosing

Time Frame

8 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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: 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 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Mihaela Plesa

Phone

440-255-1155

mplesa@frantzgroup.com

First Name & Middle Initial & Last Name or Official Title & Degree

Ahmad Bayat, MD

Phone

301-956-2523

ahmadb@amarexcro.com

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Joel Palefsky, MD

Organizational Affiliation

University of California, San Francisco

Official's Role

Principal Investigator

Facility Information:

Facility Name

Anal Neoplasia and Cancer Research and Education Center

City

San Francisco

State/Province

California

ZIP/Postal Code

94115

Country

United States

Individual Site Status

Not yet recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Arezou Sadighi

Phone

415-353-9042

arezou.sadighiakha@ucsf.edu

First Name & Middle Initial & Last Name & Degree

Joel Palefsky, MD

Facility Name

Anal Dysplasia Clinic MidWest

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60614

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Gary Bucher, MD

Phone

312-623-2625

garybuchermd@adcmidwest.com

First Name & Middle Initial & Last Name & Degree

Gary Bucher, MD

First Name & Middle Initial & Last Name & Degree

Emily Miller, APN

Facility Name

Laser Surgery Care

City

New York

State/Province

New York

ZIP/Postal Code

10011

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Taylor Ridley

Phone

212-242-6500

tridley@lasersurgerycare.com

First Name & Middle Initial & Last Name & Degree

Joseph Terlizzi, MD

First Name & Middle Initial & Last Name & Degree

Jonathan Baker, PA-C, MPAS

First Name & Middle Initial & Last Name & Degree

Shantice Branch, PA-C

12. IPD Sharing Statement

Plan to Share IPD

IPD Sharing Plan Description

No protected health information (PHI) will be shared with other researchers.

Learn more about this trial

Artesunate Suppositories for the Treatment of HIV-negative Patients With Intra-anal HSIL

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