Artesunate Ointment for Vulvar Precancer

(ART-VIN IIB Trial)

Recruiting at 4 trial locations

Overseen By Mariam AlHilli, MD

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Frantz Viral Therapeutics, LLC

Must not be taking: Efavirenz, Strong UGT inhibitors, Imiquimod, others

Disqualifiers: Pregnancy, Cancer, HIV, others

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 6 weeks

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a phase II double-blind, placebo-controlled study of artesunate ointment for the treatment of HPV-associated vulvar HSIL (usual type vulvar intraepithelial neoplasia 2/3).

Do I need to stop my current medications for the trial?

You may need to stop certain medications to participate in this trial. Specifically, you cannot use Efavirenz for HIV treatment, strong UGT inhibitors, imiquimod, cidofovir, 5-fluorouracil, or systemic corticosteroids during the study.

How is the drug Artesunate ointment unique for treating vulvar precancer?

Artesunate ointment is unique because it is a topical treatment derived from an antimalarial drug that has shown potential anticancer effects, specifically targeting HPV-associated vulvar intraepithelial neoplasia (VIN) 2/3, which is a precancerous condition. Unlike other treatments, it is applied directly to the affected area, potentially offering a more localized and less invasive option. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for adult women over 18 with a positive HPV test and biopsy-confirmed high-grade vulvar dysplasia (VIN2/3, HSIL). They must be able to consent, follow the study plan, not be pregnant or nursing, have no severe liver or kidney issues, weigh at least 50kg, and agree to use birth control. Excluded are those with low CD4 counts if HIV-positive, on certain HIV treatments or strong UGT inhibitors, using systemic corticosteroids or other cancer treatments.

Inclusion Criteria

Serum Bilirubin (total) < 2.5 x ULN

I understand the information given to me and can make decisions about my health care.

Able to collaborate with planned follow-up (transportation, compliance history, etc)

Exclusion Criteria

I am not taking any strong UGT inhibitors.

I am HIV-positive with a CD4 count below 200.

I do not have anal, vulvar, or cervical cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either artesunate or placebo ointment in four 5-day cycles at weeks 0, 2, 4, and 6

6 weeks

4 visits (in-person or virtual)

Follow-up

Participants are monitored with vulvar examinations or colposcopies at weeks 8, 18, 6-months, and 12-months

12 months

4 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Artesunate ointment

Trial Overview The study tests artesunate ointment versus placebo in treating HPV-associated vulvar HSIL. It's a phase II trial where participants don't know which treatment they're getting (double-blind) and neither do the researchers (placebo-controlled). The goal is to see if artesunate can effectively treat these lesions.

How Is the Trial Designed?

Group I: Artesunate ointment Active Control 1 Intervention

Artesunate formulated as topical ointment, 40% Four 5-day cycles of artesunate ointment every 2 weeks

Group II: Placebo ointment Placebo Group 1 Intervention

Placebo ointment Four 5-day cycles of placebo ointment every 2 weeks

Artesunate ointment is already approved in United States, European Union for the following indications:

Approved in United States as Artesunate for:

• Severe malaria

Approved in European Union as Artesunate for:

• Malaria

Who Is Running the Clinical Trial?

Frantz Viral Therapeutics, LLC

Lead Sponsor

Trials

7

Recruited

230+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

Published Research Related to This Trial

Artesunate, an antimalarial drug, is rapidly converted to its active form, dihydroartemisinin, with peak levels of artesunate reached within 5 minutes and dihydroartemisinin within approximately 37.5 minutes after oral administration in rats.

The conversion and absorption of artesunate are influenced by the pH of the gastrointestinal tract, leading to faster absorption in the stomach compared to higher pH environments, which affects the drug's overall efficacy and action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of artesunate after single oral administration to rats. Olliaro, PL., Nair, NK., Sathasivam, K., et al.[2019]

Artesunate (ART), derived from the wormwood plant, is not only a safe and effective antimalarial drug but also shows promising inhibitory effects on cancer cell proliferation, invasion, and migration.

This review highlights the potential of ART as a therapeutic option for cancer, suggesting that its clinical applications may extend beyond treating malaria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Progress on the study of the anticancer effects of artesunate. Yang, X., Zheng, Y., Liu, L., et al.[2021]

In a randomized trial with 23 colorectal cancer patients, oral artesunate showed potential anti-cancer effects, with 67% of patients experiencing significant tumor cell apoptosis compared to 55% in the placebo group.

Artesunate was generally well tolerated, and during a median follow-up of 42 months, only 1 patient in the artesunate group experienced cancer recurrence compared to 6 in the placebo group, suggesting a possible benefit in preventing cancer recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomised, Double Blind, Placebo-Controlled Pilot Study of Oral Artesunate Therapy for Colorectal Cancer. Krishna, S., Ganapathi, S., Ster, IC., et al.[2018]

Artesunate converts into dihydroartemisinin in culture medium, but this conversion is not equal in serum-free versus serum-enriched conditions, affecting their antiviral efficacy against cytomegalovirus.

The study found that dihydroartemisinin was less active than artesunate in inhibiting viral DNA synthesis, and that using fractional doses of these compounds improved their effectiveness, highlighting the importance of cellular conditions on their antiviral activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stability and antiviral activity against human cytomegalovirus of artemisinin derivatives. Flobinus, A., Taudon, N., Desbordes, M., et al.[2018]

Topical artesunate ointment demonstrated high tolerability and low toxicity in treating biopsy-confirmed HPV-associated Vulvar intraepithelial neoplasia (VIN) 2/3, with no severe adverse events reported in a trial involving 15 patients.

The treatment showed a high overall response rate (ORR) of 88.9% in the group receiving 3 treatment cycles, with 55.6% achieving complete response (CR) and evidence of complete viral clearance in a significant portion of responders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of topical artesunate for the treatment of vulvar intraepithelial neoplasia 2/3. Michener, CM., Ricci, S., AlHilli, M., et al.[2023]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of artesunate after single oral administration to rats. [2019]

2. Greece pubmed.ncbi.nlm.nih.gov

Progress on the study of the anticancer effects of artesunate. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

A Randomised, Double Blind, Placebo-Controlled Pilot Study of Oral Artesunate Therapy for Colorectal Cancer. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Stability and antiviral activity against human cytomegalovirus of artemisinin derivatives. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of topical artesunate for the treatment of vulvar intraepithelial neoplasia 2/3. [2023]