Artesunate Ointment for Anal Intraepithelial Lesions

(ART-AIN IIB-2 Trial)

Recruiting at 1 trial location

Overseen By Joseph Terlizzi, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Frantz Viral Therapeutics, LLC

Must not be taking: Immunosuppressants, Steroids, UGT inhibitors, 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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 6 weeks

48 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase II double blind, placebo-controlled, randomized study of artesunate ointment for the treatment of HIV-negative men and women who have anal high grade squamous intraepithelial lesions (anal HSIL)

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications, specifically strong UGT inhibitors and topical treatments like imiquimod or 5-fluorouracil. If you are on systemic immunosuppressants or steroids, you may also need to stop those, unless they are nasal steroids for allergies.

What data supports the effectiveness of the drug Artesunate for treating anal intraepithelial lesions?

Research shows that artesunate, a drug used to treat malaria, has also been effective in treating other conditions like certain types of cancer and viral infections. Additionally, a study found that topical artesunate was effective for treating HPV-related vulvar lesions, which are similar to anal lesions. ^{1 2 3 4 5}

How is the drug artesunate ointment unique for treating anal intraepithelial lesions?

Artesunate ointment is unique because it is a topical treatment (applied directly to the skin) that has shown promise in treating HPV-related lesions, like those in vulvar intraepithelial neoplasia, by leveraging its antiviral and potential anticancer properties, which are different from traditional surgical or systemic treatments. ^{1 2 3 6 7}

Eligibility Criteria

This trial is for HIV-negative men and women with high-grade squamous lesions in the anal area, which can be precursors to cancer. Participants should not have HPV-related conditions elsewhere like genital warts or cervical lesions.

Inclusion Criteria

Serum aspartate transaminase (SGOT/AST) < 5 x ULN

Laboratory values at Screening of:

Serum alanine transaminase (SGPT/ALT) < 5 x upper limit of normal (ULN)

Exclusion Criteria

I have cancer in the anal, vulvar, cervical, or penile area.

I am HIV positive.

I am on steroids or immunosuppressants, except for nasal treatments for allergies.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

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

6 weeks

4 visits (in-person)

Follow-up

Participants are monitored with anoscopy or high resolution anoscopy (HRA) at weeks 8, 18, 30, and 42 to evaluate response and safety

36 weeks

4 visits (in-person)

Treatment Details

Interventions

• Artesunate

Trial Overview The study tests artesunate ointment against a placebo (inactive substance) to see if it's effective in treating anal HSIL. It's a phase II trial where participants are randomly assigned to receive either the real ointment or placebo without knowing which one they get.

Participant Groups

Group I: Artesunate Experimental Treatment 1 Intervention

Group II: Placebo ointment Placebo Group 1 Intervention

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

Approved in United States as Artesunate for:

• Malaria
• Cervical intraepithelial neoplasia (CIN2/3) - Investigational

Approved in European Union as Artesunate for:

• Malaria

Who Is Running the Clinical Trial?

Frantz Viral Therapeutics, LLC

Lead Sponsor

Trials

7

Recruited

230+

Laser Surgery Care, LLC

Collaborator

Trials

1

Recruited

50+

Anal Dysplasia Clinic MidWest

Collaborator

Trials

2

Recruited

70+

Findings from Research

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]

Artesunate suppositories are effective in rapidly reducing and clearing malaria parasites, making them a strong treatment option for severe falciparum malaria.

The convenience and quick action of artesunate in suppository form make it particularly beneficial for use in rural areas where injectable treatments may not be accessible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Artesunate suppositories: an effective treatment for severe falciparum malaria in rural areas. Wilairatana, P., Viriyavejakul, P., Looareesuwan, S., et al.[2019]

Artesunate and artemisinin derivatives, when combined with praziquantel, have shown significant efficacy in treating schistosomiasis, with a statistical significance (P=0.003).

While artesunate monotherapy is less effective than praziquantel alone for schistosomiasis, it may serve as a promising chemoprophylactic option, indicating potential for preventive use (P<0.001).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of artesunate in non-malarial indications. Raffetin, A., Bruneel, F., Roussel, C., et al.[2019]

Artesunate is primarily recognized as a first-line treatment for malaria, but it also shows potential in treating various cancers and viral infections, highlighting its broad therapeutic applications.

The effectiveness of artesunate is enhanced when delivered via liposomes and can be administered through multiple routes, including intravenous and oral, which may improve its bioavailability and therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in the Therapeutic Efficacy of Artesunate. Ruwizhi, N., Maseko, RB., Aderibigbe, BA.[2022]

Intramuscular (i.m.) administration of artesunate (ARTS) is an effective alternative to intravenous (i.v.) ARTS for treating uncomplicated falciparum malaria, showing comparable pharmacokinetic profiles at equal doses.

To achieve similar plasma levels of the active metabolite dihydroartemisinin (DHA) as with i.v. ARTS, rectal DHA needs to be administered at about four times the dose, indicating that rectal administration is less bioavailable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pharmacokinetic properties of intramuscular artesunate and rectal dihydroartemisinin in uncomplicated falciparum malaria. Ilett, KF., Batty, KT., Powell, SM., 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, 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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Artesunate suppositories: an effective treatment for severe falciparum malaria in rural areas. [2019]

3. France pubmed.ncbi.nlm.nih.gov

Use of artesunate in non-malarial indications. [2019]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Recent Advances in the Therapeutic Efficacy of Artesunate. [2022]

5. England pubmed.ncbi.nlm.nih.gov

The pharmacokinetic properties of intramuscular artesunate and rectal dihydroartemisinin in uncomplicated falciparum malaria. [2021]

6. Netherlands pubmed.ncbi.nlm.nih.gov

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

7. England pubmed.ncbi.nlm.nih.gov

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