Lenacapavir for PrEP

(PURPOSE 365 Trial)

Recruiting at 25 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Gilead Sciences

Disqualifiers: Hepatitis, Liver cirrhosis, HIV, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 1

Duration: 52 weeks

300 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called lenacapavir, administered as an annual injection, to determine its safety and effectiveness in preventing HIV. The study aims to understand how the body absorbs, processes, and eliminates this medication. Individuals who have engaged in receptive anal or vaginal sex in the last six months, particularly those who have had condomless sex with partners who might have HIV, may be suitable for this trial. Participants will receive a high-dose lenacapavir injection and may take pills if the injection is unavailable. This study is crucial for developing better long-term HIV protection. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking HIV prevention method.

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

The trial information does not specify if 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 lenacapavir is likely to be safe for humans?

Research has shown that lenacapavir (LEN) is a safe option for preventing HIV. Studies have found that people using lenacapavir for pre-exposure prophylaxis (PrEP) tolerate it well, with few serious side effects reported. The FDA approved LEN as an injection every six months to prevent HIV, based on strong safety data from two clinical trials. This approval indicates that the treatment is generally safe for most people. However, discussing possible side effects with a healthcare provider before starting any new treatment is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about lenacapavir for PrEP because it offers a novel approach to HIV prevention. Unlike the standard of care, which typically involves daily oral pills like Truvada or Descovy, lenacapavir is administered as a long-acting injection that can potentially be given every six months. This delivery method could significantly improve adherence by reducing the frequency of dosing. Additionally, lenacapavir works as a capsid inhibitor, which is a new mechanism of action compared to existing PrEP medications, potentially offering more robust protection against HIV.

What evidence suggests that lenacapavir might be an effective treatment for HIV PrEP?

Research has shown that lenacapavir (LEN) is highly effective in preventing HIV. Studies found that LEN reduced the risk of HIV infection by 100% in women and 96% in a mostly male group. It is the first treatment to show no infections in some large studies. LEN works by blocking a crucial step in the virus's process, preventing it from spreading. The treatment is taken less frequently, making it a convenient choice for many. Overall, lenacapavir has shown strong promise in preventing HIV. Participants in this trial will receive LEN as part of the study's experimental treatment arms, either during the main study period or the extension phase. ^{1 2 3 4 6}

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 people at risk of HIV who've had unprotected sex or a recent STD. They must be HIV-negative, over 16 years old, and not have severe liver issues or past participation in certain HIV studies. Those with recent use of oral or subcutaneous Lenacapavir are excluded.

Inclusion Criteria

Negative local rapid fourth generation HIV-1/2 antibody (Ab)/antigen (Ag) test, central fourth generation HIV-1/2 Ab/Ag, and HIV-1 RNA quantitative nucleic acid amplification testing (NAAT) at screening

I've had unprotected sex or an STD diagnosis recently.

I am 16 years old or older.

Exclusion Criteria

Past or current participation in HIV vaccine or HIV broadly neutralizing antibody study unless participant provides documentation of receipt of placebo (ie, not active product)

I do not have severe liver problems or cirrhosis.

I am showing signs or symptoms that may indicate I have HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LEN 3000 mg injection once on Day 1 and oral LEN 600 mg on Day 1 and Day 2

52 weeks

1 visit (in-person) for injection, additional visits if oral LEN is needed

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants receive LEN 3000 mg injection once approximately one year after their initial dose

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• Lenacapavir

Trial Overview The study tests Lenacapavir as a once-yearly injection to prevent HIV (PrEP). It aims to understand how the drug works in the body over time and its safety when given as an annual shot compared to tablets.

How Is the Trial Designed?

Group I: Lenacapavir (LEN) Experimental Treatment 2 Interventions

Participants with an indication for pre-exposure prophylaxis will receive for approximately 52 weeks: * LEN 3000 mg injection once on Day 1 * Oral LEN 600 mg on Day 1 and Day 2 during the Main Study Period Participant will receive additional oral LEN if IM injection are not available.

Group II: LEN Extension Phase Experimental Treatment 2 Interventions

Participants with an indication for pre-exposure prophylaxis will receive LEN 3000 mg injection once on Day 1 (approximately one year after their initial dose) during the Extension Phase. Participants will receive oral LEN if IM injections are not available.

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

Citations

1. who.int who.int/publications/i/item/9789240111608

Guidelines on lenacapavir for HIV prevention and testing ... LEN, administered twice a year as PrEP, has been shown to be highly effective at reducing the risk of HIV acquisition. In this guideline, WHO ...

2. gilead.com gilead.com/news/news-details/2025/yeztugo-lenacapavir-is-now-the-first-and-only-fda-approved-hiv-prevention-option-offering-6-months-of-protection

Yeztugo® (Lenacapavir) Is Now the First and Only FDA ... ... PrEP preferred less frequent dosing.” FDA approval of Yeztugo is supported by high efficacy and demonstrated safety data in two clinical trials.

3. prepwatch.org prepwatch.org/products/lenacapavir-for-prep/

Injectable Lenacapavir for PrEP Effectiveness. Shown to be highly effective at preventing HIV in two large Phase III clinical trials, PURPOSE 1 and PURPOSE 2. Early results ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1555415525000431

Lenacapavir for HIV PrEP: Interim Phase III Clinical Data ... Interim data suggest lenacapavir is highly efficacious, distinctly being the first PrEP regimen to ever show zero infections during Phase III clinical trials.

5. cdc.gov cdc.gov/mmwr/volumes/74/wr/mm7435a1.htm

Clinical Recommendation for the Use of Injectable ... The two trials reported LEN efficacy at reducing HIV infection as 100% among females and 96% among a primarily male trial population, compared ...

6. askgileadmedical.com askgileadmedical.com/len4prep/dosing-admin/

Lenacapavir for PrEP | Dosing & Administration ... LEN for PrEP is indicated for pre‑exposure prophylaxis (PrEP) to reduce the risk of sexually acquired HIV-1 in adults and adolescents weighing at least 35 kg ...