Lenacapavir + F/TDF for HIV Prevention

(PURPOSE 3 Trial)

Not currently recruiting at 12 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Female

Trial Phase: Phase 2

Sponsor: Gilead Sciences

Disqualifiers: HIV, Hepatitis, Liver cirrhosis, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how lenacapavir functions in the body and assesses its safety when combined with F/TDF (a combination of the antiretroviral drugs Emtricitabine and Tenofovir Disoproxil Fumarate) to prevent HIV in cisgender women in the U.S. Participants will either receive lenacapavir through injections and pills or take F/TDF pills daily to compare these treatments. The trial seeks cisgender women who have had condomless sex with a cisgender man in the past year and meet other lifestyle criteria, such as having multiple partners or a history of certain sexually transmitted infections (STIs). As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that lenacapavir (LEN) has been tested in people with HIV without raising major safety concerns. In one study, only 1.2% of participants taking LEN reported problems, a notably low rate. The FDA has approved LEN for preventing HIV in some cases, although it remains under study for this purpose.

Emtricitabine/tenofovir disoproxil fumarate (F/TDF) already has FDA approval for preventing HIV. It is generally safe and well-tolerated, with mild side effects like nausea or headaches occurring infrequently.

Overall, current studies indicate that both LEN and F/TDF are safe for use in preventing HIV. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Lenacapavir for HIV prevention because it offers a new way to protect against the virus. Unlike the standard daily oral pills like Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF), Lenacapavir is administered via subcutaneous injections every six months, potentially improving adherence for those who find daily dosing challenging. Additionally, Lenacapavir works by targeting a different part of the virus, offering a novel mechanism of action that could enhance its effectiveness and help those who might not respond well to current treatments. This unique delivery method and mechanism make Lenacapavir a promising option in the fight against HIV.

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

Research has shown that lenacapavir, which participants in this trial may receive, effectively prevents HIV. Studies have found it can reduce the risk of contracting HIV by up to 96% compared to usual rates. Administered every six months, this long-lasting treatment may help individuals adhere to their prevention plan. Meanwhile, emtricitabine/tenofovir disoproxil fumarate (F/TDF), another treatment option in this trial, can lower the risk of HIV by almost 90% when taken regularly. Both treatments offer promising methods for HIV prevention. ^{6 7 8 9 10}

Who Is on the Research Team?

Gilead Study Director

Principal Investigator

Gilead Sciences

Are You a Good Fit for This Trial?

This trial is for US cisgender women at high risk of HIV, including those who've exchanged sex for commodities, had condomless sex with a man in the past year, used noninjection drugs recreationally, or have multiple male sexual partners. Women must test negative for HIV and hepatitis B to join.

Inclusion Criteria

You have a score of 2 or higher for Cut Down, Annoyed, Guilty and Eye Opener indicating alcohol dependence; additionally you regularly consume four drinks or more at once as part of binge-drinking.

You are not infected with the hepatitis B virus.

I have had unprotected sex with a man in the past year.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Randomized Phase

Participants receive either subcutaneous lenacapavir or oral F/TDF for 52 weeks

52 weeks

Multiple visits for drug administration and monitoring

PK Tail Phase

Participants transition to or continue receiving F/TDF for 78 weeks

78 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF)
• Lenacapavir

Trial Overview The study tests Lenacapavir (LEN) injections and tablets alongside Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) to prevent HIV. It aims to understand how LEN works in the body, its safety as pre-exposure prophylaxis (PrEP), and if women find these methods acceptable.

How Is the Trial Designed?

Group I: Randomized Phase: Lenacapavir (LEN) Group Experimental Treatment 2 Interventions

Participants will receive subcutaneous (SC) lenacapavir (LEN) 927 mg on Day 1 and Week 26 and oral LEN 600 mg on Days 1 and 2.

Group II: Randomized Phase: Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) Group Experimental Treatment 1 Intervention

Participants will receive oral F/TDF (200/300 mg) daily for 52 weeks.

Group III: PK Tail Phase: F/TDF Experimental Treatment 1 Intervention

After the completion of the Randomized Phase, participants in LEN group will be transitioned to receive F/TDF and participants in F/TDF group will continue to receive F/TDF in the PK Tail Phase. All participants will receive F/TDF, once daily for 78 weeks beginning 26 weeks after the last LEN injection.

Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Truvada for:

• Pre-exposure prophylaxis (PrEP) for HIV-1 infection

Approved in European Union as Truvada for:

• Pre-exposure prophylaxis (PrEP) for HIV-1 infection

Approved in Canada as Truvada for:

• Pre-exposure prophylaxis (PrEP) for HIV-1 infection

Who Is Running the Clinical Trial?

Gilead Sciences

Lead Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

HIV Prevention Trials Network

Collaborator

Trials

31

Recruited

569,000+

Published Research Related to This Trial

In a phase 3 trial with 663 HIV-infected adults, switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) showed similar effectiveness in maintaining viral suppression, with 88.6% of TAF users and 89.1% of TDF users achieving HIV-1 RNA levels below 50 copies per milliliter after 96 weeks.

Patients switching to TAF experienced improvements in kidney function and bone mineral density compared to those remaining on TDF, indicating that TAF may offer a safer profile with better long-term health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief Report: Long-Term (96-Week) Efficacy and Safety After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in HIV-Infected, Virologically Suppressed Adults. Raffi, F., Orkin, C., Clarke, A., et al.[2022]

The fixed-dose combination (FDC) inhaler containing mometasone furoate and formoterol fumarate showed comparable pharmacokinetics to individual inhalers, indicating that the combination does not alter the absorption of either drug when used together.

In a study involving healthy subjects, the systemic exposure levels of mometasone furoate and formoterol were similar whether administered as a combination or as separate inhalers, suggesting that the FDC is safe and effective for asthma and potentially for COPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of potential for pharmacokinetic interaction between mometasone furoate and formoterol fumarate after oral inhalation from a fixed-dose combination metered-dose inhaler device. Kosoglou, T., Hubbell, J., Johnson-Levonas, AO., et al.[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 combination of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) demonstrated additive to synergistic anti-HIV activity in vitro, particularly effective against both wild-type and mutant strains of the virus, based on studies in human T leukaemic cells and peripheral blood mononuclear cells (PBMCs).

Both drugs were efficiently converted to their active metabolites in the tested cells, with significant increases in the levels of these metabolites when used together, suggesting that their combined use enhances their effectiveness as a dual NRTI backbone in HIV-1 treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro evaluation of the anti-HIV activity and metabolic interactions of tenofovir and emtricitabine. Borroto-Esoda, K., Vela, JE., Myrick, F., et al.[2015]

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]

In a clinical trial involving 1055 participants with moderate to very severe COPD, the combination of mometasone furoate/formoterol fumarate (MF/F) significantly improved lung function (FEV1) compared to individual components, showing effectiveness as a treatment.

Both doses of MF/F (400/10 μg and 200/10 μg) were well tolerated, with low rates of pneumonia (≤1.0%) and no significant differences in adverse events across treatment groups, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of a fixed-dose combination of mometasone furoate and formoterol fumarate in subjects with moderate to very severe COPD: results from a 52-week Phase III trial. Tashkin, DP., Doherty, DE., Kerwin, E., et al.[2021]

In a 4-month study involving 2179 adult asthma patients, the extrafine formulation of beclomethasone/formoterol (BDP/F pMDI HFA) significantly improved asthma control, as shown by a decrease in the Asthma Control Questionnaire score from 1.62 to 0.94 (p < 0.001).

Patients reported better compliance with their medication, with those forgetting to take their medication dropping from 49.7% to 27.1% (p < 0.001), and most patients expressed satisfaction with the inhaler device, preferring it over dry powder inhalers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improvement of asthma control in adult patients using extrafine inhaled beclomethasone/formoterol fixed combination as maintenance therapy as well as maintenance and reliever therapy - CONTROL study. Dębowski, T., Marko, M., Rogala, B., et al.[2023]

Mometasone furoate and formoterol fumarate (MF/F) is an effective fixed-dose combination therapy for asthma in patients aged 12 and older, showing improvements in lung function and quality of life while reducing asthma exacerbations.

Clinical safety studies of MF/F, lasting up to one year, indicate a low incidence of both local and systemic side effects, suggesting it is a safe option for long-term asthma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mometasone furoate/formoterol in the treatment of persistent asthma. Berger, WE.[2015]

The investigational coformulation of efavirenz (EFV), emtricitabine (FTC), and tenofovir disoproxil fumarate (TDF) is bioequivalent to the individual components, indicating it can be used interchangeably without loss of efficacy.

The study involved 48 healthy subjects, and all treatments were well tolerated, suggesting that the coformulation is safe for use in the target population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence of efavirenz/emtricitabine/tenofovir disoproxil fumarate single-tablet regimen. Mathias, AA., Hinkle, J., Menning, M., et al.[2020]

In a study involving 2251 patients with moderate to very severe COPD, the fixed-dose combination of mometasone furoate/formoterol fumarate (MF/F) significantly improved lung function, with greater increases in forced expiratory volume (FEV1) compared to placebo and individual components, particularly at the higher dose of MF/F 400/10 μg.

The treatment also led to better health status as measured by the St George's Respiratory Questionnaire and reduced exacerbation rates, with a similar safety profile to placebo, indicating that MF/F is both effective and safe for COPD management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety characteristics of mometasone furoate/formoterol fumarate fixed-dose combination in subjects with moderate to very severe COPD: findings from pooled analysis of two randomized, 52-week placebo-controlled trials. Tashkin, DP., Doherty, DE., Kerwin, E., et al.[2022]

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/NCT00458393

Study Details | NCT00458393 | Emtricitabine/Tenofovir ... This study will evaluate the safety and efficacy of chemoprophylaxis for HIV prevention in men who have sex with men (MSM) who are at high risk for HIV ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12492902/

Long-term safety and efficacy of emtricitabine and tenofovir ... ... emtricitabine and tenofovir disoproxil fumarate showed non-inferior efficacy for HIV prevention and improved bone mineral density and ...

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

Long-term safety and efficacy of emtricitabine ... - The Lancet Approximately 78–82% of participants reported taking study medication more than 95% of the time across all study visits.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2013/021752s035lbl.pdf

Truvada (emtricitabine tenofovir disoproxil fumarate) tablets ... TRUVADA is indicated in combination with safer sex practices for pre-exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults at high ...

7. 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 ...

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

EMTRICITABINE AND TENOFOVIR DISOPROXIL FUMARATE Emtricitabine and tenofovir disoproxil fumarate tablets are not approved for the treatment of chronic HBV infection, and the safety and efficacy of ...

10. 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 ...