TAF/EVG Vaginal Insert for HIV Prevention

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

60 Participants Needed

Trial Summary

What is the purpose of this trial?

MATRIX-001 will examine the safety, PK, modeled PD, and acceptability of inserts containing the combination of TAF and EVG applied vaginally, daily for 3 days, then every other day for 14 days. The inserts are ultimately intended to be the basis of an event-driven, on-demand method for prevention of HIV and HSV sexual infection.

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 data supports the effectiveness of the TAF/EVG vaginal insert for HIV prevention?

Research shows that tenofovir alafenamide (TAF) and elvitegravir (EVG) are effective in treating HIV, with TAF offering improved safety for kidneys and bones compared to older drugs. Additionally, studies in macaques suggest that TAF/EVG inserts can be effective for HIV prevention when used rectally, indicating potential for similar effectiveness when used vaginally. ^{1 2 3 4 5}

Is the TAF/EVG vaginal insert safe for humans?

Tenofovir alafenamide (TAF) is known to have improved kidney and bone safety compared to older versions of the drug, and it has been used safely in combination with other drugs for HIV treatment in adults. While specific safety data for the TAF/EVG vaginal insert is not available, TAF has been studied in various forms and shown to be generally safe. ^{1 2 3 4 6}

How is the TAF/EVG vaginal insert drug different from other HIV prevention options?

The TAF/EVG vaginal insert is unique because it is designed for on-demand use, meaning it can be used just before sexual activity, unlike daily PrEP (pre-exposure prophylaxis) pills. It combines tenofovir alafenamide (TAF), which has improved safety for kidneys and bones, with elvitegravir (EVG), and is administered as a fast-dissolving insert, offering a novel route of administration compared to traditional oral tablets. ^{1 2 3 4 7}

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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 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]

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]

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]

References

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

Elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide for the treatment of HIV in adults. [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and efficacy of topical inserts containing tenofovir alafenamide fumarate and elvitegravir administered rectally in macaques. [2022]

3. United States 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. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Tenofovir alafenamide and elvitegravir loaded nanoparticles for long-acting prevention of HIV-1 vaginal transmission. [2022]

5. United States 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. [2023]

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

Chemoprophylaxis With Oral Emtricitabine and Tenofovir Alafenamide Combination Protects Macaques From Rectal Simian/Human Immunodeficiency Virus Infection. [2021]

7. United States 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. [2022]