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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests an ointment called artesunate (an artemisinin derivative) to determine its effectiveness in treating anal HSIL, a type of high-grade lesion in the anal area. The study compares the effects of the artesunate ointment with a placebo, which contains no active treatment. Suitable participants include those diagnosed with anal HSIL, who are HIV-negative, and have tested positive for anal HPV. Participants must not be receiving certain other treatments, such as chemotherapy or steroids, and must not have conditions like HIV. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

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

Research shows that artesunate is generally safe for treating certain types of lesions. Studies have found that artesunate suppositories are safe and well-tolerated for treating anal high-grade squamous intraepithelial lesions (anal HSIL). This suggests that the ointment form being tested might also be well-tolerated. Additionally, other studies have used artesunate safely for different types of lesions, providing some confidence in its safety for this trial. However, since this trial is in an early stage, more information is needed about the safety of the ointment form. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for anal HSIL?

Unlike the standard treatments for anal intraepithelial lesions, which often involve surgical procedures or topical chemotherapy agents, artesunate ointment is derived from a natural compound found in the sweet wormwood plant. Researchers are excited about artesunate because it offers a non-invasive, topical option that could potentially reduce side effects associated with more aggressive treatments. Additionally, artesunate has shown promise due to its unique mechanism of action, which involves inhibiting viral replication and promoting the death of abnormal cells, potentially offering a more targeted approach to treating these lesions.

What evidence suggests that artesunate ointment might be an effective treatment for anal HSIL?

Research has shown that artesunate ointment, which participants in this trial may receive, might help treat anal high-grade squamous intraepithelial lesions (anal HSIL). Earlier studies found artesunate to be safe and to cause few side effects when used for similar lesions, such as those linked to HPV on the vulva. Initial research on using artesunate inside the anus suggests it may help shrink these lesions in some patients. Although more studies are needed, these results indicate that artesunate ointment could be a possible treatment for anal HSIL. ^{1 5 6 7 8}

Are You a Good Fit for This Trial?

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 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 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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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, 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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10723659/

A phase I study of intra-anal artesunate (suppositories) to treat ... With the limitation of the small cohort size, subgroup analyses suggest that artesunate may be more effective in the treatment of anal HSIL of ...

2. journals.plos.org journals.plos.org/plosone/article/file?type=printable&id=10.1371/journal.pone.0295647

A phase I study of intra-anal artesunate (suppositories) to treat ... Patients were enrolled from June 8, 2017 to December 16, 2020, and fol- lowed for safety, tolerability and efficacy outcomes with a cutoff date ...

3. withpower.com withpower.com/trial/artesunate-ointment-for-anal-intraepithelial-lesions-3fae8

Artesunate Ointment for Anal Intraepithelial Lesions Topical artesunate ointment demonstrated high tolerability and low toxicity in treating biopsy-confirmed HPV-associated Vulvar intraepithelial neoplasia (VIN) ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8951414/

Recent Advances in the Therapeutic Efficacy of Artesunate While the artesunate decreased parasitaemia, epoxyazadiradione increased Hb level by acting against PMIF.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05555862

Artesunate Suppositories for the Treatment of HIV-negative ... Eligible participants in this study are randomized 2:1 to receive either artesunate or placebo suppositories for the treatment of anal HSIL.

6. journals.plos.org journals.plos.org/plosone/article?id=10.1371/journal.pone.0295647

A phase I study of intra-anal artesunate (suppositories) to treat ... Conclusions. Intra-anal artesunate is a safe and well-tolerated treatment for anal HSIL and may be a promising addition in the therapeutic ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12411702/

Feasibility of Intravaginal Artesunate as an Adjuvant HPV & ... Preclinical and early-phase clinical trials indicate that topical artesunate is active against HPV-associated anogenital lesions, including cervical precancer, ...

8. idpjournal.biomedcentral.com idpjournal.biomedcentral.com/articles/10.1186/s40249-023-01152-6

New clinical application prospects of artemisinin and its ... Clinical studies have suggested that artemisinin and its derivatives are safe for tumor treatment, and might have effects on different kinds of ...