Artesunate Vaginal Inserts for Cervical Dysplasia

(ART-CIN_IIB Trial)

Recruiting at 8 trial locations

Overseen By Ahmad Bayat, MD

Age: 18+

Sex: Female

Travel: May Be Covered

Trial Phase: Phase 2

Sponsor: Frantz Viral Therapeutics, LLC

Must not be taking: Immunosuppressants

Disqualifiers: Pregnancy, Autoimmune disease, 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

78 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a phase II double blind, placebo-controlled, randomized study of Artesunate vaginal inserts for the treatment of women who have cervical high grade intraepithelial neoplasia (CIN2/3).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are taking immunosuppressive medication.

Is artesunate safe for human use?

Artesunate, used in malaria treatment, has been tested in pregnant women and was well tolerated with no drug-related adverse effects. In trials for cervical and vulvar conditions, artesunate was evaluated for safety and showed promise, but more research is needed to confirm its safety for these specific uses. ^{1 2 3 4 5}

How is the drug Artesunate unique for treating cervical dysplasia?

Artesunate vaginal inserts for cervical dysplasia are unique because they use an artemisinin derivative, which is different from the commonly used prostaglandin-based treatments like dinoprostone for cervical conditions. This treatment offers a novel approach by potentially leveraging the anti-inflammatory and anti-cancer properties of artesunate, which are not typical of standard cervical dysplasia treatments. ^{6 7 8 9 10}

Eligibility Criteria

This trial is for adult women aged 25 or older with a biopsy-confirmed diagnosis of high-grade cervical lesions (CIN2/3), weighing at least 50kg, and not pregnant or breastfeeding. Participants must be able to consent and agree to use birth control until week 28 of the study. Women who are immunocompromised, have concurrent cancer (except nonmelanoma skin lesions), HIV-seropositive, or have active autoimmune diseases cannot join.

Inclusion Criteria

I have a confirmed diagnosis of a high-grade cervical precancer.

I weigh at least 110 pounds.

I agree to use birth control until week 28 of the study.

Exclusion Criteria

Are you immune compromised in any way?

I have no other cancers except for non-dangerous skin lesions.

I have a diagnosis of early-stage cervical cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive three 5-day cycles of artesunate or placebo vaginal inserts at weeks 0, 2, and 4

6 weeks

3 visits (telehealth)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a LEEP procedure at week 17

40 weeks

3 visits (in-person) at weeks 6, 17, and 40

Treatment Details

Interventions

• Artesunate

Trial Overview The study is testing Artesunate vaginal inserts versus placebo inserts in treating high-grade cervical pre-cancerous lesions caused by HPV. It's a phase II trial where participants are randomly assigned to receive either the treatment or placebo without knowing which one they're getting.

Participant Groups

Group I: Artesunate vaginal insert Experimental Treatment 1 Intervention

Participants will receive three 5-day cycles of artesunate vaginal inserts, 200mg/day, at week 0, week 2, week 4.

Group II: Placebo vaginal inserts Placebo Group 1 Intervention

Participants will receive three 5-day cycles of placebo vaginal inserts, at week 0, week 2, and week 4.

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+

Morehouse School of Medicine

Collaborator

Trials

22

Recruited

16,300+

Amarex Clinical Research

Collaborator

Trials

28

Recruited

1,700+

Harris Health System (L.B.J. Hospital)

Collaborator

Trials

1

Recruited

80+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

M.D. Anderson Cancer Center

Collaborator

Trials

3,107

Recruited

1,813,000+

University of Michigan

Collaborator

Trials

1,891

Recruited

6,458,000+

Findings from Research

In a study involving 83 pregnant women in Thailand treated with artesunate or artemether for multidrug-resistant malaria, the medications were well tolerated with no drug-related adverse effects reported.

The treatment resulted in a high live birth rate of 88%, with no congenital abnormalities observed in the newborns, indicating that these artemisinin derivatives are safe for use during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Artemisinin derivatives in the treatment of falciparum malaria in pregnancy. McGready, R., Cho, T., Cho, JJ., 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]

In a Phase I study involving 28 patients with biopsy-confirmed CIN2/3, self-administered vaginal artesunate inserts were found to be safe and well-tolerated, with only mild and self-limited adverse events reported.

The treatment led to histologic regression in 67.9% of subjects, and 47.4% of those who showed regression also cleared the HPV genotypes present at baseline, indicating potential efficacy in treating cervical lesions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A first-in-human proof-of-concept trial of intravaginal artesunate to treat cervical intraepithelial neoplasia 2/3 (CIN2/3). Trimble, CL., Levinson, K., Maldonado, L., et al.[2022]

In a study involving 3428 pregnant women with malaria across four African countries, dihydroartemisinin-piperaquine showed the highest PCR-adjusted cure rate (99.2%) and an acceptable safety profile, making it the most effective treatment option among those tested.

Artemether-lumefantrine, while associated with the fewest adverse effects, had the lowest cure rate (94.8%) and provided the shortest post-treatment prophylaxis compared to other treatments, indicating a trade-off between safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Four Artemisinin-Based Treatments in African Pregnant Women with Malaria. Pekyi, D., Ampromfi, AA., Tinto, H., et al.[2022]

In a study involving 3428 pregnant women with malaria across four African countries, dihydroartemisinin-piperaquine showed the highest cure rate (99.2%) and an acceptable safety profile, making it the most effective treatment option among those tested.

Artemether-lumefantrine had the fewest adverse effects but provided the shortest post-treatment prophylaxis, indicating a trade-off between safety and long-term effectiveness compared to other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Four artemisinin-based treatments in African pregnant women with malaria. Pekyi, D., Ampromfi, AA., Tinto, H., et al.[2022]

The dinoprostone vaginal insert (Cervidil®; Propess®) is an effective and well-tolerated method for cervical ripening in women at term, providing a controlled release of the medication to facilitate the labor process.

While there is a risk of uterine hyperstimulation associated with its use, this side effect is typically reversible upon removal of the device, highlighting its safety profile for both mothers and babies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dinoprostone Vaginal Insert: A Review in Cervical Ripening. Shirley, M.[2021]

Both the slow release vaginal PGE2 insert (Propess) and intracervical PGE2 gel (Prepidil) were similarly effective in inducing labor, with success rates of 67% and 65% respectively, based on a study of 103 pregnant women.

Propess demonstrated a safer profile with fewer patients requiring multiple applications of prostaglandin (5.9% vs. 55.8% for Prepidil) and a lower incidence of cesarean sections due to fetal distress (2 cases vs. 8 cases for Prepidil), suggesting it may be a preferable option for cervical ripening.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Dinoprostone: slow release vaginal insert (Propess) and intracervical gel (Prepidil) for the induction of labour with unriped cervix]. Grignaffini, A., Soncini, E., Anfuso, S., et al.[2013]

A study comparing a 10-mg PGE2 vaginal insert to 3-mg PGE2 tablets for labor induction found no significant differences in vaginal delivery rates or cesarean section rates between the two methods, with both groups having similar outcomes.

However, the PGE2 vaginal insert allowed for easier management of uterine hyperstimulation, as it could be removed to stop the condition, while the tablet group often required additional medical interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial of vaginal prostaglandin E2 for induction of labor. Insert vs. tablet. Rabl, M., Joura, EA., Yücel, Y., et al.[2013]

A systematic review of nine trials found that the dinoprostone 10 mg controlled-release vaginal insert is similarly effective as other vaginal or cervical prostaglandins for cervical ripening, with no significant differences in delivery rates within 24 hours.

The rates of uterine hypertonus and cesarean deliveries were also comparable between the dinoprostone insert and alternative treatments, indicating that the insert is a safe option for labor induction without increased risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dinoprostone vaginal insert for cervical ripening and labor induction: a meta-analysis. Hughes, EG., Kelly, AJ., Kavanagh, J.[2019]

In a multicenter randomized trial involving patients with low Bishop scores (0-4) at term, the Dinoprostone vaginal insert was found to be more effective than the cervical gel, requiring fewer patients to use additional induction methods (25% vs. 47.1%).

The vaginal insert also resulted in a significantly shorter induction-to-delivery time (approximately 5 hours and 46 minutes less), while maintaining comparable safety outcomes, such as cesarean rates and fetal distress, suggesting it is a safe and efficient option for labor induction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized study on removable PGE2 vaginal insert versus PGE2 cervical gel for cervical priming and labor induction in low-Bishop-score pregnancy. Strobelt, N., Meregalli, V., Ratti, M., et al.[2019]

References

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

Artemisinin derivatives in the treatment of falciparum malaria in pregnancy. [2019]

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

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

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

A first-in-human proof-of-concept trial of intravaginal artesunate to treat cervical intraepithelial neoplasia 2/3 (CIN2/3). [2022]

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

Four Artemisinin-Based Treatments in African Pregnant Women with Malaria. [2022]

5. Malawi pubmed.ncbi.nlm.nih.gov

Four artemisinin-based treatments in African pregnant women with malaria. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Dinoprostone Vaginal Insert: A Review in Cervical Ripening. [2021]

7. Italy pubmed.ncbi.nlm.nih.gov

[Dinoprostone: slow release vaginal insert (Propess) and intracervical gel (Prepidil) for the induction of labour with unriped cervix]. [2013]

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

A randomized trial of vaginal prostaglandin E2 for induction of labor. Insert vs. tablet. [2013]

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

Dinoprostone vaginal insert for cervical ripening and labor induction: a meta-analysis. [2019]

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

Randomized study on removable PGE2 vaginal insert versus PGE2 cervical gel for cervical priming and labor induction in low-Bishop-score pregnancy. [2019]