Artesunate suppositories for anal HSIL

(anal HSIL HIV- Trial)

Not currently recruiting at 2 trial locations

Overseen By Ahmad Bayat, 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: 6

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment using artesunate suppositories to address high-grade squamous intraepithelial lesions (HSIL), which are precancerous changes in anal tissue. The researchers aim to determine if artesunate, an artemisinin derivative, can effectively treat these lesions compared to a placebo. Participants undergo four treatment cycles, receiving either artesunate suppositories or placebo suppositories. The trial seeks men and women who are HIV-negative and have been diagnosed with anal HSIL that persists after previous biopsies or treatments. As a Phase 2 trial, this 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 join this trial. Specifically, you cannot use strong UGT inhibitors, imiquimod, or 5-fluorouracil during the study. If you're on systemic immunosuppressants or steroids, you also cannot participate.

Is there any evidence suggesting that Artesunate suppositories are likely to be safe for humans?

Research has shown that artesunate suppositories are generally safe for people. One study used these suppositories to treat anal HSIL, and most participants did not experience serious side effects, indicating good tolerance. Another study found that artesunate and similar compounds are safe for treating various tumors, suggesting potential safety and effectiveness for other health issues as well. In summary, current evidence indicates that artesunate suppositories are safe for humans, with very few reports of negative reactions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for anal dysplasia, which often involve surgical procedures or topical creams, artesunate suppositories offer a unique approach by using a well-known antimalarial drug in a new form. Artesunate is derived from sweet wormwood and has shown potential antiviral and anticancer properties, which are being explored in this trial. Researchers are excited about artesunate because it targets the condition directly within the anal canal through suppositories, potentially reducing systemic side effects and offering a non-invasive alternative. This new delivery method could make treatment more convenient and comfortable for patients, while also accelerating the timeline for seeing results.

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

Research has shown that artesunate, when used as a suppository, may help treat anal high-grade squamous intraepithelial lesions (anal HSIL). Studies suggest that artesunate might be effective due to its easy absorption by the body. Early results from small studies indicated it could reduce anal HSIL, but further research is necessary to confirm this. In this trial, participants will receive either artesunate suppositories or placebo suppositories. Artesunate and similar compounds have also shown promise in stopping tumor growth. These early findings make artesunate a hopeful option for those dealing with anal HSIL. ^{1 2 4 6 7}

Who Is on the Research Team?

Joel Palefsky, MD

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for HIV-negative adults over 18 with a specific type of anal lesion called high-grade squamous intraepithelial lesions (HSIL). They must have normal liver and kidney function, weigh at least 50kg, and women must use birth control. People with low-grade dysplasia only, HIV, other cancers being treated, or on strong immune system suppressants can't join.

Inclusion Criteria

I understand the details of the clinical trial and can give my consent.

I agree to use birth control throughout the study.

I have a confirmed high-grade anal lesion.

Exclusion Criteria

I am HIV positive.

I am using imiquimod or 5-FU during the study.

I have a high-grade precancerous condition in my anal area.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive four 5-day cycles of artesunate or placebo suppositories at weeks 0, 2, 4, and 6

6 weeks

At least 2 visits (in-person), remaining visits may be virtual

Follow-up

Participants are monitored with anoscopy or high resolution anoscopy (HRA) at weeks 8, 18, 30, and 42. Non-responders at week 18 undergo standard of care ablation

42 weeks

4 visits (in-person)

Extension/Long-term follow-up

Participants who have at least partial response at week 18 are followed with HRA at week 30. Participants with anal HSIL at weeks 30 or 42 are followed according to standard of care procedures

42 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Artesunate
• Placebo

Trial Overview The study tests Artesunate suppositories against placebo in treating anal HSIL. It's a phase II trial where participants are randomly assigned to either the treatment or placebo group without knowing which one they receive (double-blind).

How Is the Trial Designed?

Group I: Artesunate suppositories Experimental Treatment 1 Intervention

Four 5-day cycles of artesunate suppositories

Group II: Placebo suppositories Placebo Group 1 Intervention

Four 5-day cycles of placebo suppositories

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+

Anal Dysplasia Clinic MidWest

Collaborator

Trials

2

Recruited

70+

Laser Surgery Care

Collaborator

Trials

3

Recruited

510+

Amarex CRO

Collaborator

Trials

1

Recruited

20+

University of California, San Francisco

Collaborator

Trials

2,636

Recruited

19,080,000+

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

Recent Advances in the Therapeutic Efficacy of Artesunate ART has better absorption, solubility, and pharmacokinetics than artemisinin. Its administration can be intramuscular, oral, rectal, and ...

3. 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 ...

4. 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 might have a better clinical effect in tumor treatment by inhibiting tumor ...

5. researchgate.net researchgate.net/publication/376579043_A_phase_I_study_of_intra-anal_artesunate_suppositories_to_treat_anal_high-grade_squamous_intraepithelial_lesions

A phase I study of intra-anal artesunate (suppositories) to ... Results The maximal tolerated dose was 400 mg, administered in 3 cycles. All adverse events associated with the use 200- and 400-mg artesunate ...

6. extranet.who.int extranet.who.int/prequal/sites/default/files/document_files/55%20Nonclinical%20overview%20artemisinin%20derivatives_Jan2016.pdf

Artemisinin Derivatives: Summary of Nonclinical Safety ... The results generally demonstrated nearly equal sensitivity of drug-resistant isolates as compared to drug-sensitive ones. As mentioned in the ...

7. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.596697/full

Safety and Efficacy of Adjunctive Therapy With Artesunate ... Conclusion: No significant differences in safety and efficacy were observed between the artesunate monotherapy group and the artesunate + ...