Lenacapavir for HIV Prevention

(PURPOSE 2 Trial)

Not currently recruiting at 108 trial locations

Overseen By Gilead Clinical Study Information Center

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Gilead Sciences

Must not be taking: HIV PrEP, HIV PEP

Disqualifiers: Hepatitis, Liver cirrhosis, 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

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

Compensation: Varies

Number of Visits: 53

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests lenacapavir, a medication aimed at preventing HIV infections. Researchers aim to determine its effectiveness in individuals who engage in condomless receptive anal sex with partners assigned male at birth and are at risk for HIV-1. Participants will take lenacapavir either by injection or as a pill, sometimes alongside a placebo (a substance with no active drug), to compare outcomes. Eligible participants include those who have recently engaged in condomless receptive anal sex with multiple partners or have had certain sexually transmitted infections. Consider joining to explore new preventive options for HIV. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking HIV prevention method.

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 is generally well-tolerated for preventing HIV. In one study involving 2,183 participants taking lenacapavir, only 1.2% reported safety concerns, compared to 0.3% in a group using a standard treatment. This suggests lenacapavir is relatively safe, with few participants experiencing issues. However, lenacapavir remains under study and has not yet received FDA approval for HIV prevention. It is crucial to consult a healthcare professional about potential risks and benefits before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Lenacapavir is unique because it offers a new approach to HIV prevention through its long-acting formulation. Unlike current daily oral medications like Truvada or Descovy, lenacapavir is administered via a subcutaneous injection every six months, which could significantly improve adherence for users. Researchers are excited about this treatment as it targets the HIV capsid, a novel mechanism that could enhance effectiveness and potentially reduce side effects. This long-acting, innovative approach might offer a more convenient and possibly more reliable method for preventing HIV.

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

Research has shown that lenacapavir, one of the treatments studied in this trial, is a promising option for preventing HIV. It has reduced new HIV cases by 96% compared to the usual infection rate. One study found that lenacapavir completely prevented new HIV cases, outperforming daily Truvada, a common prevention pill. Administered as an injection every six months, this treatment can help individuals adhere to their prevention plan more easily. Clinical experts recommend lenacapavir as a safe and effective choice for preventing HIV. Participants in this trial may receive lenacapavir or other treatments such as F/TDF, depending on their assigned study arm. ^{3 6 7 8 9}

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 individuals at risk of HIV infection who have had condomless receptive anal sex with male partners, used stimulants during sex recently, or had certain sexually transmitted infections. They must have a kidney function test result (eGFR) ≥ 60 mL/min and not previously taken long-acting PrEP or oral PrEP in the past 12 weeks.

Inclusion Criteria

I've had unprotected receptive anal sex with 2 or more partners in the last 3 months.

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

My kidney function, measured by eGFR, is 60 mL/min or higher.

Exclusion Criteria

Randomized Phase:

I have acute or chronic hepatitis A, B, or C.

I have received an HIV vaccine or broadly neutralizing antibody.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Blinded Phase

Participants receive either SC lenacapavir or placebo every 26 weeks, with oral F/TDF or PTM LEN for approximately 52 weeks

52 weeks

Visits every 26 weeks

PK Tail Phase

Participants who discontinue early or choose not to continue in the LEN OLE Phase receive oral F/TDF or F/TAF for 78 weeks

78 weeks

Visits every 13 weeks

LEN Open-Label Extension (OLE) Phase

Participants continue or switch to SC LEN 927 mg every 26 weeks, with visits every 13 weeks, until LEN is available or study is discontinued

Variable

Visits every 13 weeks

Follow-up

Participants transition to local PrEP services and have a 30-day follow-up visit after study completion or early exit

30 days

1 visit

What Are the Treatments Tested in This Trial?

Interventions

• F/TAF
• F/TDF
• Lenacapavir

Trial Overview The study tests Lenacapavir's effectiveness in preventing HIV. Participants will receive either oral Lenacapavir, subcutaneous Lenacapavir, placebos, or other pre-exposure prophylaxis drugs like F/TDF (and F/TAF for US participants).

How Is the Trial Designed?

Group I: Randomized Blinded Phase: Placebo LEN + F/TDF Experimental Treatment 3 Interventions

Participants will receive the following for up to approximately 52 weeks: * SC LEN placebo every 26 weeks * Oral F/TDF 200/300 mg once daily * PTM Oral LEN on Days 1 and 2 Participants will receive oral LEN placebo if SC injections are not available.

Group II: Randomized Blinded Phase: LEN + Placebo-to-match (PTM) F/TDF Experimental Treatment 3 Interventions

Participants will receive the following for up to approximately 52 weeks: * Subcutaneous (SC) lenacapavir (LEN) 927 mg every 26 weeks * Oral PTM Emtricitabine/Tenofovir Disoproxil Fumarate (F/TDF) once daily * Oral LEN 600 mg on Days 1 and 2 Participants will receive oral LEN if SC injections are not available.

Group III: Pharmacokinetic (PK) Tail Phase Experimental Treatment 2 Interventions

Participants who prematurely discontinue study drug during the Randomized Blinded Phase and participants that were randomized to LEN who choose not to continue in the LEN OLE Phase will transition to the PK Tail Phase. Participants will receive oral F/TDF (or Emtricitabine/Tenofovir Alafenamide (F/TAF) for US participants only) once daily for 78 weeks to cover the PK tail and complete visits every 13 weeks (+/- 7 days). Upon unblinding, participants who were randomized to F/TDF in the Randomized Blinded Phase who decline to participate in the LEN OLE Phase will complete the ESDD visit, transition to local HIV prevention services, and return for a 30-day follow-up visit.

Group IV: LEN Open-Label Extension (OLE) Phase Experimental Treatment 2 Interventions

Participants will be offered entry into LEN OLE Phase, following completion of primary analysis, if LEN demonstrates acceptable safety and efficacy in the Randomized Blinded Phase. Participants randomized to LEN will continue to receive SC LEN 927 mg, every 26 weeks (± 7 days), and have study visits every 13 weeks (± 7 days). Participants randomized to F/TDF will switch to SC LEN 927 mg on OLE Day 1, Week 26 and every 26 weeks thereafter. Participants will also receive oral LEN 600 mg on OLE Days 1 and 2. All participants in LEN OLE Phase will complete the phase, once LEN becomes available or the sponsor decides to discontinue the study, whichever happens first. After completing LEN OLE Phase or study discontinuation, participants will transition to local PrEP, including LEN or other options. If a participant exits early, they will complete an early study drug discontinuation (ESDD), be referred to local PrEP services if needed, and have a 30-day follow-up visit.

Lenacapavir is already approved in United States for the following indications:

Approved in United States as Sunlenca for:

• Treatment of HIV

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

Published Research Related to This Trial

Lenacapavir (LEN) is a novel capsid inhibitor that offers a unique treatment option for heavily treatment-experienced (HTE) HIV-1 patients, demonstrating efficacy in achieving viral suppression and immune restoration when combined with other antiretrovirals.

Administered subcutaneously twice a year, lenacapavir provides a convenient dosing schedule, making it a well-tolerated and effective addition to existing HIV treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenacapavir: A Novel Long-Acting Capsid Inhibitor for HIV. Tailor, MW., Chahine, EB., Koren, D., et al.[2023]

Lenacapavir is the first FDA-approved capsid inhibitor for treating multidrug-resistant HIV-1, specifically for heavily treatment-experienced adults whose current therapies are failing due to resistance or safety issues.

In a phase 3 clinical trial, lenacapavir significantly reduced viral load compared to placebo, and it is administered as a long-acting injection every 6 months, although 63% of participants experienced injection site reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenacapavir: A first-in-class capsid inhibitor for the treatment of highly treatment-resistant HIV. Prather, C., Lee, A., Yen, C.[2023]

Lenacapavir (LEN) is effective against HIV-1, showing no cross-resistance with entry inhibitors in a study of 72 participants, making it a viable treatment option for heavily treatment-experienced individuals with multidrug resistance.

In the CAPELLA study, only 13% of participants developed resistance mutations to LEN after 52 weeks, indicating that LEN maintains its efficacy even in patients with a history of treatment failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cross-resistance to entry inhibitors and lenacapavir resistance through Week 52 in study CAPELLA. Margot, N., Pennetzdorfer, N., Naik, V., et al.[2023]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2411858

Twice-Yearly Lenacapavir for HIV Prevention in Men and ... Lenacapavir has been shown to be efficacious for the prevention of HIV infection in cisgender women,14 and capsid inhibitors, including ...

2. gilead.com gilead.com/news/news-details/2024/full-efficacy-and-safety-results-for-gilead-investigational-twice-yearly-lenacapavir-for-hiv-prevention-presented-at-aids-2024

Full Efficacy and Safety Results for Gilead Investigational ... Additionally, compared to once-daily Truvada, lenacapavir reduced HIV incidence by 100%, a result that was statistically superior (IRR 0; 95% CI ...

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

Clinical Recommendation for the Use of Injectable ... LEN is a highly effective and safe PrEP option administered every 6 months, which provides the potential to improve PrEP adherence and thus ...

4. thelancet.com thelancet.com/journals/lanam/article/PIIS2667-193X(25)00156-5/fulltext

Lenacapavir: a potential game changer for HIV prevention ... In PURPOSE 2, lenacapavir had a 96% efficacy for PrEP compared to the background HIV incidence and was superior to F/TDF among men who have sex ...

5. who.int who.int/news/item/26-09-2024-long-acting-injectable-lenacapavir-continues-to-show-promising-results-for-hiv-prevention

Long-acting injectable lenacapavir continues to show ... Lenacapavir demonstrated a 96% reduction in HIV incidence compared to background HIV incidence (2.37 per 100 person-years) and was 89% more ...

6. askgileadmedical.com askgileadmedical.com/docs/sunlenca/sunlenca-safety-overview

For HCP's | Sunlenca® (lenacapavir) Safety Overview The primary safety assessment of LEN was based on data from HTE adult participants with HIV who received LEN in a phase 2/3 trial (CAPELLA; N=72) through Week ...

7. gilead.com gilead.com/-/media/files/pdfs/medicines/hiv/sunlenca/sunlenca_pi.pdf

sunlenca_pi.pdf The primary safety assessment of SUNLENCA was based on data from heavily treatment-experienced adult participants with HIV who received SUNLENCA in a. Phase ...

8. gilead.com gilead.com/news/news-details/2025/gilead-presents-new-hiv-research-data-at-eacs-2025--driving-scientific-innovation-in-treatment-and-prevention

Gilead Presents New HIV Research Data at EACS 2025 The use of lenacapavir in virologically suppressed people with HIV is investigational and the safety and efficacy of this use have not been ...

9. clinicalinfo.hiv.gov clinicalinfo.hiv.gov/en/guidelines/perinatal/safety-toxicity-arv-agents-capsid-inhibitors-lenacapavir-sunlenca

Appendix B: Lenacapavir - Safety and Toxicity in Pregnancy LEN is under evaluation for HIV pre-exposure prophylaxis (PrEP); LEN is not FDA approved for HIV prevention. Human Studies in Pregnancy. Pharmacokinetics. No ...