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 trial tests an ointment called artesunate for treating precancerous lesions in the vulva linked to HPV, a virus. The goal is to determine if this ointment can effectively reduce or eliminate these high-grade lesions. Participants will receive either the artesunate ointment or a placebo (a non-active treatment) for comparison. Women with a recent biopsy showing high-grade vulvar dysplasia (abnormal cell growth) and a positive HPV test may be suitable for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that artesunate ointment is likely to be safe for humans?

Research has shown that artesunate ointment is generally safe and carries a low risk of side effects. In earlier studies, patients using this ointment for vulvar conditions tolerated it well, experiencing few side effects. Evidence also suggests that the treatment might be effective for its intended purpose. Although these results are promising, they stem from early research focused on safety and tolerability. More studies are needed to confirm these findings, but initial results support the ointment's safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for vulvar precancer, which typically involve surgical procedures or topical chemotherapies, artesunate ointment offers a non-invasive approach using a novel active ingredient derived from the plant Artemisia annua. This ointment provides a targeted treatment with potential anti-cancer properties, as artesunate is known for its ability to interfere with cancer cell growth. Researchers are excited about artesunate ointment because it promises a potentially effective alternative with fewer side effects and greater convenience for patients, who can apply it directly to the affected area.

What evidence suggests that artesunate ointment might be an effective treatment for vulvar precancer?

This trial will compare artesunate ointment with a placebo ointment for treating HPV-related vulvar HSIL, a condition that can lead to cancer. Research has shown that artesunate ointment might help treat this condition. Studies have found that this ointment is generally safe and has few side effects. In small clinical trials, patients responded well, indicating that artesunate could be an effective treatment without surgery. Early results suggest it might lessen the severity of these lesions, offering hope for those seeking non-surgical options. ^{1 2 3 4 6}

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

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]

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]

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]

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. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37839312/

Safety and efficacy of topical artesunate for the treatment ... Topical artesunate for treatment of high-grade VIN shows high tolerability, low toxicity and evidence for clinical response in this initial small series.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06075264

Phase II Study of Artesunate Ointment for the Treatment ... This is a phase II double-blind, placebo-controlled study of artesunate ointment for the treatment of HPV-associated vulvar HSIL (usual type vulvar ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03792516

Artesunate Ointment for the Treatment of High Grade ... This is a Phase I, proof-of-concept treatment study to evaluate the safety, tolerability and feasibility of topical artesunate ointment to treat high grade ...

4. consultqd.clevelandclinic.org consultqd.clevelandclinic.org/phase-ii-trials-evaluate-topical-treatment-for-vulvar-and-cervical-dysplasias

Trials Evaluate Topical Treatment for Dysplasias - Consult QD Phase II Trials Evaluate Topical Treatment for Vulvar and Cervical Dysplasias. Artesunate ointment shows promise as a non-surgical alternative.

5. pure.johnshopkins.edu pure.johnshopkins.edu/en/publications/safety-and-efficacy-of-topical-artesunate-for-the-treatment-of-vu

Safety and efficacy of topical artesunate for the treatment ... Objective: To evaluate the safety, tolerability, and efficacy of topical artesunate ointment for treatment of biopsy-confirmed Human papillomavirus ...

6. go.drugbank.com go.drugbank.com/drugs/DB09274/clinical_trials?conditions=DBCOND0028937%2CDBCOND0035860&phase=1&purpose=treatment&status=completed

Artesunate Completed Phase 1 Trials for Vulvar Diseases ... Artesunate Completed Phase 1 Trials for Vulvar Diseases / Vulvar Dysplasia Treatment ; NCT03792516. Artesunate Ointment for the Treatment of High Grade Vulvar ...