Lenacapavir for HIV Prevention

(PURPOSE 2 Trial)

Recruiting at 102 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

3295 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing lenacapavir, a drug that may help prevent HIV. It targets people who are at risk of getting HIV. The drug works by stopping the virus from making more copies of itself. Lenacapavir was developed by Gilead Sciences Inc. and has been approved for use in combination with other treatments.

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 lenacapavir safe for humans?

Lenacapavir has been generally well tolerated in clinical trials, with common mild to moderate side effects like injection site reactions, stomach issues, and headaches. It has been studied for treating multidrug-resistant HIV, and ongoing studies are evaluating its use for HIV prevention. ^{1 2 3 4 5}

What makes the drug Lenacapavir unique for HIV prevention?

Lenacapavir is unique because it is a long-acting injectable drug that targets the HIV-1 capsid (a protein shell of the virus), allowing for dosing every six months, which reduces the need for daily pills. This makes it different from most current HIV treatments that require daily administration. ^{1 2 3 4 6}

What data supports the effectiveness of the drug Lenacapavir for HIV prevention?

Lenacapavir has shown effectiveness in treating multidrug-resistant HIV, as it is a long-acting drug that can be used in combination with other treatments. It has been approved for use in people with limited treatment options, demonstrating its potential in managing HIV. ^{1 2 3 7 8}

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: PK Tail Phase Experimental Treatment 2 Interventions

Participants who prematurely discontinue study drug during 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 II: LEN Open-Label Extension (OLE) Phase Experimental Treatment 2 Interventions

Participants will be offered entry into the LEN OLE Phase, following the 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 the LEN OLE Phase will complete the phase, once LEN becomes available or the sponsor decides to discontinue the study, whichever happens first. After completing the 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 ESDD visit, be referred to local PrEP services if needed, and have a 30-day follow-up visit.

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

Participants will receive the following for 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 IV: Blinded Phase: LEN + Placebo-to-match (PTM) F/TDF Experimental Treatment 3 Interventions

Participants will receive the following for 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

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

Lenacapavir: A Novel Long-Acting Capsid Inhibitor for HIV. [2023]

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

Efficacy and safety of the novel capsid inhibitor lenacapavir to treat multidrug-resistant HIV: week 52 results of a phase 2/3 trial. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Lenacapavir administered every 26 weeks or daily in combination with oral daily antiretroviral therapy for initial treatment of HIV: a randomised, open-label, active-controlled, phase 2 trial. [2023]

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

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

5. England pubmed.ncbi.nlm.nih.gov

Lenacapavir: a twice-yearly treatment for adults with multidrug-resistant HIV infection and limited treatment options. [2023]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Lenacapavir: A novel injectable HIV-1 capsid inhibitor. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Cross-resistance to entry inhibitors and lenacapavir resistance through Week 52 in study CAPELLA. [2023]

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

Lenacapavir and the novel HIV-1 capsid inhibitors: an emerging therapy in the management of multidrug-resistant HIV-1 virus. [2023]