PrEP Pod-IVR for HIV Prevention

(PrEP-Pod-IVR Trial)

Age: 18 - 65

Sex: Female

Trial Phase: Phase < 1

Sponsor: Oak Crest Institute of Science

Must not be taking: Anticoagulants, NSAIDs, Immunomodulators, others

Disqualifiers: Pregnancy, HIV, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method to prevent HIV using a ring that delivers medication inside the body. Researchers aim to assess the effectiveness and acceptability of this treatment by comparing a real medication ring with a placebo (an inactive version). The real medication ring contains Tenofovir Disoproxil Fumarate (TDF) and Emtricitabine (FTC), drugs used for HIV prevention. The study involves female participants who are HIV-negative, in good health, and willing to use the ring and follow study guidelines. Participants will also share their experiences through surveys and interviews. This trial suits women committed to using study-provided protection and abstaining from certain activities as required. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking HIV prevention efforts.

Do I have to stop taking my current medications for the trial?

Yes, you may need to stop taking certain medications. The trial requires participants to abstain from using specific medications, such as blood thinners like Warfarin and certain NSAIDs (like ibuprofen) before biopsies, as well as rectally or vaginally administered medications during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of Tenofovir Disoproxil Fumarate (TDF) and Emtricitabine (FTC) is generally safe for preventing HIV. Studies have found that most people tolerate this combination well.

For those considering joining a clinical trial, it's important to know that the FDA has already approved TDF/FTC for HIV prevention. This approval means it has been tested in many people and shown to be safe. Most side effects are mild, such as headaches or an upset stomach.

In summary, research supports the safety of TDF/FTC. Participants in this trial can feel confident in the treatment's strong safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the PrEP Pod-IVR treatment for HIV prevention because it offers a novel delivery method that sets it apart from traditional oral medications like Truvada. Unlike daily pills, this investigational treatment uses a pod-intravaginal ring (pod-IVR) to deliver the active ingredients, Tenofovir Disoproxil Fumarate (TDF) and Emtricitabine (FTC), directly at the site where the virus might enter the body. This local delivery method may improve adherence and reduce systemic side effects, making it a promising alternative for those who struggle with daily pill regimens. By potentially offering more consistent protection with less frequent dosing, this new approach could significantly enhance HIV prevention strategies.

What evidence suggests that this trial's treatments could be effective for HIV prevention?

Research shows that taking Tenofovir Disoproxil Fumarate (TDF) and Emtricitabine (FTC) as pre-exposure prophylaxis (PrEP) can significantly lower the risk of contracting HIV. Studies have found that maintaining certain levels of these drugs in the blood can reduce HIV risk by up to 90%. In another study, daily use of TDF/FTC reduced the chance of contracting HIV by 44% among men who have sex with men and transgender women. This treatment works by preventing the virus from multiplying in the body. While PrEP is effective, it is not 100% guaranteed and does not protect against HIV strains resistant to these drugs. Participants in this trial will receive either the TDF-FTC pod-IVR or a placebo pod-IVR, with the sequence of treatments varying between the two study arms. ^{6 7 8 9 10}

Who Is on the Research Team?

Kathleen L Vincent, MD

Principal Investigator

University of Texas

Are You a Good Fit for This Trial?

This trial is for HIV-negative women aged 18-45 in good health, with regular menstrual cycles or controlled by certain contraceptives. They must not be pregnant, breastfeeding, or planning pregnancy and should agree to avoid vaginal products and intercourse as specified. Male partners can participate if they consent to interviews and use provided condoms.

Inclusion Criteria

My male partner meets the study's specific health criteria.

Abstain from use of any vaginal products other than study products for the duration of the study

Abstain from receptive oral, vaginal, or anal intercourse during specific periods

Exclusion Criteria

I haven't used any specified medications or products in the last 4 weeks.

Participating in another research study involving drugs or medical devices within the specified time frames

I have not had any gynecologic or genital procedures in the last 60 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo a 28-day pre-ring baseline assessment period

4 weeks

1 visit (in-person)

Treatment Stage 2

Participants receive either TDF-FTC pod-IVR or placebo pod-IVR for 28 days

4 weeks

Multiple visits (in-person and virtual)

Washout Period

A 2-week washout period between treatments

2 weeks

Treatment Stage 3

Participants receive the alternate pod-IVR (TDF-FTC or placebo) for 28 days

4 weeks

Multiple visits (in-person and virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Tenofovir Disoproxil Fumarate (TDF)-Emtricitabine (FTC)

Trial Overview The study tests a TDF-FTC pod-IVR (a vaginal ring for HIV prevention) against a placebo over two stages, each lasting 28 days with a washout period in between. Participants will also provide feedback through surveys and interviews about the product's feel and acceptability.

How Is the Trial Designed?

Group I: Arm 2 Experimental Treatment 2 Interventions

Arm 2 will receive the placebo pod-IVR for Stage 2 followed by the Tenofovir Disoproxil Fumarate (TDF)-Emtricitabine (FTC) pod-IVR during Stage 3.

Group II: Arm 1 Experimental Treatment 2 Interventions

Arm 1 will receive the Tenofovir Disoproxil Fumarate (TDF)-Emtricitabine (FTC) pod-IVR for Stage 2 followed by the placebo pod-IVR during Stage 3.

Who Is Running the Clinical Trial?

Oak Crest Institute of Science

Lead Sponsor

Trials

3

Recruited

120+

The Miriam Hospital

Collaborator

Trials

252

Recruited

39,200+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

University of California, Los Angeles

Collaborator

Trials

1,594

Recruited

10,430,000+

University of California, San Diego

Collaborator

Trials

1,215

Recruited

1,593,000+

Vanderbilt University

Collaborator

Trials

714

Recruited

6,143,000+

The University of Texas Medical Branch, Galveston

Collaborator

Trials

263

Recruited

55,400+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

Tenofovir disoproxil fumarate-emtricitabine (TDF/FTC) has been approved for HIV pre-exposure prophylaxis (PrEP) since 2012, and while initial uptake was slow, recent surveys indicate growing acceptance among key populations.

Ongoing studies aim to improve PrEP implementation by identifying at-risk individuals in primary care settings and evaluating its use in HIV-discordant couples, highlighting the need for better education among healthcare providers and addressing financial barriers for underinsured patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antiretroviral pre-exposure prophylaxis implementation in the United States: a work in progress. Mayer, KH., Hosek, S., Cohen, S., et al.[2022]

Using tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for preexposure prophylaxis (PrEP) is effective in preventing HIV-1 infections, with resistance to the drugs being rare if PrEP is started before infection occurs.

However, starting PrEP during an undiagnosed acute HIV-1 infection can lead to higher rates of drug resistance, particularly to tenofovir, highlighting the importance of screening for HIV before initiating PrEP.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Should we fear resistance from tenofovir/emtricitabine preexposure prophylaxis? Parikh, UM., Mellors, JW.[2018]

Tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) are effective in reducing the risk of HIV infection by 74 to 92% when taken as pre-exposure prophylaxis (PrEP) with detectable drug levels.

While TDF-FTC can cause side effects like nausea and decreased bone mineral density, these risks can be managed through regular monitoring by healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug safety evaluation of oral tenofovir disoproxil fumarate-emtricitabine for pre-exposure prophylaxis for human immunodeficiency virus infection. Trang, TP., Dong, BJ., Kojima, N., et al.[2017]

The study found that the combination of emtricitabine and tenofovir alafenamide (F/TAF) was safe and well-tolerated among HIV-uninfected women, with significantly lower gastrointestinal side effects compared to the older F/TDF combination.

F/TAF demonstrated higher concentrations of the active form of tenofovir (TFV-DP) in peripheral blood mononuclear cells and vaginal tissues compared to F/TDF, suggesting it may be a more effective option for HIV pre-exposure prophylaxis in women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Pharmacokinetics of a Tenofovir Alafenamide Fumarate-Emtricitabine based Oral Antiretroviral Regimen for Prevention of HIV Acquisition in Women: A Randomized Controlled Trial. Thurman, AR., Schwartz, JL., Cottrell, ML., et al.[2022]

Tenofovir disoproxil fumarate (TDF) and its combination with emtricitabine (FTC), marketed as Truvada®, have been shown to be effective in preventing HIV infection when taken orally, either daily or intermittently, in various populations including men who have sex with men and serodiscordant couples.

Topical tenofovir gel has also demonstrated effectiveness in preventing HIV infection in women, highlighting the versatility of tenofovir-based interventions in HIV prophylaxis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-exposure chemoprophylaxis of HIV infection: quo vadis? Clercq, ED.[2015]

Tenofovir disoproxil fumarate coformulated with emtricitabine (TDF/FTC) is a safe and highly effective medication for preventing HIV transmission, yet only about 200,000 Americans have started using it for pre-exposure prophylaxis (PrEP), leaving 80%-90% of those at highest risk without access.

Barriers to PrEP uptake include costs, anticipated side effects, and stigma, but innovative strategies like engaging nonmedical staff and developing new technologies are being explored to improve adherence and make PrEP more accessible.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PrEP 1.0 and Beyond: Optimizing a Biobehavioral Intervention. Mayer, KH., Allan-Blitz, LT.[2020]

Oral tenofovir disoproxil and emtricitabine (FTC) for HIV preexposure prophylaxis (PrEP) is generally safe and well tolerated, with common gastrointestinal side effects that typically resolve within weeks.

While there is a slight decline in kidney function (eGFR) and bone mineral density (BMD) associated with the treatment, these changes are not clinically significant and tend to resolve after stopping the medication, making it a viable option for most adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of oral tenofovir disoproxil - emtricitabine for HIV preexposure prophylaxis in adults. Liegeon, G.[2022]

Topical tenofovir gel and daily oral tenofovir/emtricitabine (FTC/TDF) have shown significant efficacy in preventing HIV-1, with reductions in acquisition rates of 39% and 44% respectively in various studies involving different populations.

While tenofovir gel was effective in African women and oral FTC/TDF showed efficacy in men who have sex with men (MSM) and serodiscordant couples, some studies in African women found no efficacy, prompting further investigation into the reasons behind these differences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tenofovir-based pre-exposure prophylaxis for HIV prevention: evolving evidence. Celum, C., Baeten, JM.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6453722/

Review of real-world implementation data on emtricitabine ... Patients should be made aware that PrEP is not 100% effective and will not prevent the acquisition of HIV strains resistant to FTC and TDF. Cost effectiveness.

2. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2816036

HIV Preexposure Prophylaxis With Emtricitabine and ... Indeed, participants with tenofovir diphosphate concentrations indicative of taking 4 to 6 doses per week had a nearly 90% HIV risk reduction in ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00705679

Safety and Effectiveness of TFV 1% Gel, TDF Tablets ... A new approach to HIV prevention currently being studied includes the use of microbicides, substances that kill microbes. Tenofovir disoproxil fumarate ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1684118225000453

Measurements of tenofovir-diphosphate and emtricitabine ... The iPrEx study first reported that daily use of PrEP with TDF/FTC resulted in a 44 % reduction in HIV acquisition among MSM and transgender women. The PROUD ...

5. thelancet.com thelancet.com/journals/lanhiv/article/PIIS2352-3018(21)00071-0/abstract

Long-term safety and efficacy of emtricitabine ... - The Lancet The primary efficacy outcome was incident HIV infection. Incidence of HIV-1 infection per 100 person-years was assessed when the last ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/pepfar/090049PI.pdf

EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE Emtricitabine and tenofovir disoproxil fumarate tablets do not cure HIV-1 or AIDS. If you have HIV-1 infection, you must keep taking HIV-1 medicines to ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9010110/

Safety review of tenofovir disoproxil fumarate/emtricitabine ... In summary, TDF/FTC PrEP is a potent and recommended HIV prevention option, with a demonstrably good safety profile, including in pregnancy. While safety data ...

8. mayoclinic.org mayoclinic.org/drugs-supplements/emtricitabine-and-tenofovir-oral-route/description/drg-20061833

Emtricitabine and tenofovir (oral route) - Side effects & ... This medicine will not cure HIV infection or AIDS. It works by lowering the amount of HIV in the blood and helps the immune system. This may ...

9. prepwatch.org prepwatch.org/products/oral-prep-tdf-ftc/

Oral PrEP TDF/FTC The safety and efficacy of TDF/FTC and TDF/3TC is well-established. Policy and program decisions are guided by both data from the original ...

10. gilead.com gilead.com/-/media/files/pdfs/medicines/hiv/truvada/truvada_pi.pdf

truvada_pi.pdf Emtricitabine: In addition to the adverse reactions reported in adults, anemia and hyperpigmentation were observed in 7% and 32%, respectively, of pediatric ...