TAF/EVG Vaginal Insert for HIV Prevention

No longer recruiting at 2 trial locations

Overseen By Karen Dominguez, MPH

Age: 18 - 65

Sex: Female

Trial Phase: Phase 1

Sponsor: Eastern Virginia Medical School

Must not be taking: Anticoagulants, Stimulants, Inhaled nitrates

Disqualifiers: HIV, Hepatitis B, Syphilis, others

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 8

Duration: 3 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaginal insert that combines TAF and EVG (Tenofovir Alafenamide/Elvitegravir), which might help prevent HIV and herpes infections. The trial aims to determine if the insert is safe and acceptable for use. Participants will use the insert daily for three days, then every other day for two weeks. Ideal candidates are women who have regular periods, are HIV-negative, have had vaginal sex, and are in a mutually monogamous relationship. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that you cannot continue using any medications that are contraindicated (not allowed) as listed in Appendix III. It's best to discuss your current medications with the study team to see if they are allowed.

What prior data suggests that the TAF/EVG vaginal insert is safe for use?

Research has shown that the TAF/EVG (tenofovir alafenamide and elvitegravir) vaginal insert has undergone safety testing. In earlier studies, a single dose of this insert was generally well-tolerated. These studies found that the insert offered strong protection against HIV and similar viruses when used vaginally.

When tested for rectal use, the insert also proved to be safe, suggesting it is likely safe for vaginal use as well. It is important to note that this trial remains in the early stages, with researchers still confirming its safety in humans. However, earlier results are promising, indicating the insert could be a safe option for preventing HIV. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

The TAF/EVG vaginal insert is unique because it combines two antiretroviral drugs, tenofovir alafenamide (TAF) and elvitegravir (EVG), in a single, easy-to-use vaginal insert specifically designed for HIV prevention. Unlike oral pre-exposure prophylaxis (PrEP) options, which require daily pills, this insert offers a direct delivery method that could potentially enhance convenience and adherence. Researchers are excited about this treatment because it targets HIV at the site of potential infection, which could provide effective protection with lower systemic exposure, minimizing side effects.

What evidence suggests that the TAF/EVG vaginal insert might be an effective treatment for HIV prevention?

Research has shown that TAF/EVG vaginal inserts, which participants in this trial may receive, could offer a new method to prevent HIV. These inserts help protect against infections in both the vaginal and rectal areas. Similar treatments, such as tenofovir gel, have successfully reduced HIV and herpes infections. Early tests of TAF/EVG inserts indicated they are safe and effective in the body. Overall, TAF/EVG inserts show promise, but further studies are needed to confirm their effectiveness. ^{2 3 4 6 7}

Who Is on the Research Team?

Leila Mansoor, BPharm, PhD

Principal Investigator

Centre for the AIDS Programme of Research in South Africa

Nelly Mugo, MBChB

Principal Investigator

Kenya Medical Research Institute

Are You a Good Fit for This Trial?

This trial is for healthy women aged 18-50 who are not pregnant, do not plan to become pregnant or breastfeed during the study, and use effective contraception. They must have a normal cervicovaginal exam, no history of significant allergies to study products, no recent treatments for certain STIs or use of investigational drugs/devices. Participants should be HIV-negative with an intact uterus and cervix.

Inclusion Criteria

I am over 21 and have had a normal Pap smear in the last 3 years.

My cervicovaginal area is healthy.

I was assigned female at birth.

Exclusion Criteria

History of sensitivity/allergy to any component of the study product, topical anesthetic, cellulose based thrombogenic material, or to both silver nitrate and Monsel's solution

I experience chronic or acute symptoms in my vulvar, vaginal, or cervical area.

Positive HIV test at Screening or Enrollment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TAF/EVG or placebo vaginal inserts daily for 3 days, then every other day for 14 days

3 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and pharmacokinetics

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TAF/EVG vaginal insert

Trial Overview

The MATRIX-001 study tests the safety and pharmacokinetics (how the drug moves through the body) of TAF/EVG vaginal inserts compared to placebo inserts. The goal is to see if these can prevent HIV/HSV infection when used before sexual activity. Women will use them daily for three days then every other day for two weeks.

How Is the Trial Designed?

Group I: Active Experimental Treatment 1 Intervention

TAF/EVG (20/16mg) vaginal insert

Group II: Placebo Placebo Group 1 Intervention

Matching placebo insert

TAF/EVG vaginal insert is already approved in United States for the following indications:

Approved in United States as Tenofovir Alafenamide for:

• Chronic hepatitis B
• HIV treatment and prevention in men who have sex with men (when used in combination with emtricitabine)

Approved in United States as Elvitegravir for:

• HIV treatment (when used in combination with other ARVs)

Who Is Running the Clinical Trial?

Eastern Virginia Medical School

Lead Sponsor

Trials

77

Recruited

16,500+

CONRAD

Collaborator

Trials

60

Recruited

11,800+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

Centre for the AIDS Programme of Research in South Africa

Collaborator

Trials

23

Recruited

20,800+

Kenya Medical Research Institute

Collaborator

Trials

186

Recruited

1,408,000+

United States Agency for International Development (USAID)

Collaborator

Trials

212

Recruited

1,519,000+

Published Research Related to This Trial

The study demonstrated that a single rectal insert of tenofovir alafenamide (TAF) and elvitegravir (EVG) resulted in rapid and high levels of the drugs in rectal tissue, but only provided 72.6% efficacy against rectal SHIV challenges.

Using two inserts significantly increased drug levels in rectal tissues, leading to a much higher efficacy of 93.1%, highlighting the importance of adequate drug coverage for effective HIV prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and efficacy of topical inserts containing tenofovir alafenamide fumarate and elvitegravir administered rectally in macaques. Makarova, N., Singletary, T., Peet, MM., et al.[2022]

In a study involving macaques, the combination of tenofovir alafenamide (TAF) and emtricitabine (FTC) effectively prevented simian/human immunodeficiency virus (SHIV) infection, demonstrating its potential as a pre-exposure prophylaxis (PrEP) for HIV.

All control macaques were infected after exposure to SHIV, while all macaques treated with FTC/TAF remained protected, indicating strong efficacy of this treatment combination in preventing viral infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemoprophylaxis With Oral Emtricitabine and Tenofovir Alafenamide Combination Protects Macaques From Rectal Simian/Human Immunodeficiency Virus Infection. Massud, I., Mitchell, J., Babusis, D., et al.[2021]

The study showed that nanoparticles containing tenofovir alafenamide (TAF) and elvitegravir (EVG) provided significant protection against HIV-1 in humanized mice, with 100% of mice remaining uninfected when challenged 4 days after nanoparticle injection.

TAF+EVG nanoparticles demonstrated a much lower effective concentration for inhibition (0.002 μg/ml) compared to the drug solution (0.78 μg/ml), and the nanoparticles maintained detectable drug levels in tissues for 14 days, indicating a more effective and sustained delivery method.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenofovir alafenamide and elvitegravir loaded nanoparticles for long-acting prevention of HIV-1 vaginal transmission. Mandal, S., Prathipati, PK., Kang, G., et al.[2022]

In a study of 242 HIV-1-infected patients with mild to moderate renal impairment, switching to a once-daily regimen of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) showed no significant change in kidney function after 48 weeks, indicating its safety for this population.

Patients experienced significant improvements in proteinuria and bone mineral density, with 92% maintaining viral suppression, demonstrating the efficacy of E/C/F/TAF without the need for dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Patients With Renal Impairment: 48-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study. Pozniak, A., Arribas, JR., Gathe, J., et al.[2021]

In a study involving 1733 participants over 96 weeks, both tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) were effective in achieving similar rates of viral suppression in HIV-1, with 86.6% and 85.2% of participants respectively maintaining HIV-1 RNA levels below 50 c/mL.

TAF showed advantages over TDF, including less decline in bone mineral density, improved kidney function markers, and no cases of proximal tubulopathy, indicating that TAF is a safer and better-tolerated option for initial HIV-1 treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief Report: A Randomized, Double-Blind Comparison of Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate, Each Coformulated With Elvitegravir, Cobicistat, and Emtricitabine for Initial HIV-1 Treatment: Week 96 Results. Wohl, D., Oka, S., Clumeck, N., et al.[2022]

The single tablet regimen elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) is as effective as the traditional TDF-based regimen for treating HIV in naive patients and shows improved efficacy in those switching from TDF-based treatments.

E/C/F/TAF demonstrates significant safety benefits, including improved renal function and bone mineral density compared to TDF, making it a promising option for enhancing the tolerability of HIV treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide for the treatment of HIV in adults. Bonora, S., Calcagno, A., Trentalange, A., et al.[2021]

In a study involving 29 pregnant women living with HIV, the pharmacokinetics of Tenofovir alafenamide (TAF) showed no significant differences between the second and third trimesters compared to postpartum, indicating consistent drug exposure during pregnancy.

TAF was found to be minimally present in maternal delivery samples and undetectable in cord blood and infant washout samples, suggesting a short half-life and supporting the safety of TAF use during pregnancy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of Tenofovir Alafenamide With Boosted Protease Inhibitors in Pregnant and Postpartum Women Living With HIV: Results From IMPAACT P1026s. Brooks, KM., Pinilla, M., Stek, AM., et al.[2023]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9643401/

Pharmacokinetics and efficacy of topical inserts containing ...

TAF/EVG inserts are a promising new HIV prevention modality that provides dual compartment protection against both vaginal and rectal infection. Compared to ...

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10154607/

A phase I study to assess safety, pharmacokinetics, and ...

Topical tenofovir (TFV), as a 1% vaginal gel, was effective in reducing the incidence of HIV-1 (Abdool Karim et al., 2010) and herpes simplex ...

3.

sciencedirect.com

sciencedirect.com/science/article/pii/S0168365924008216

Formulation development of dual-compartment topical ...

Here we describe the formulation development of a dual-compartment topical insert containing tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG)

4.

academic.oup.com

academic.oup.com/jid/article/230/3/696/7657362

A Phase 1 Clinical Trial to Assess the Safety and ...

In a phase 1 study, a fast-dissolving insert containing tenofovir alafenamide and elvitegravir administered rectally was shown to be safe in ...

5.

mdpi.com

mdpi.com/1999-4923/16/3/348?

Preclinical and Early Clinical Development of Tenofovir ...

In summary, the TAF/EVG inserts are stable, easy to manufacture, low-cost, acceptable, and show highly promising preclinical and clinical ...

6.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/37153145/

A phase I study to assess safety, pharmacokinetics, and ...

A single dose of TAF/EVG inserts met PK benchmarks, with PK data supporting an extended window of high mucosal protection.

7.

mpts101.org

mpts101.org/taf-elvitegravir-topical-insert/

TAF / Elvitegravir Topical Insert

The TAF/EVG insert dosed either vaginally (single dose) or rectally (double dose) provides strong protection against vaginal or rectal SHIV exposure.