Lenacapavir + OBR for Drug-Resistant HIV

(CAPELLA Trial)

Not currently recruiting at 84 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Gilead Sciences

Must be taking: Antiretrovirals

Disqualifiers: Hepatitis C, others

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: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called lenacapavir (also known as Sunlenca) for individuals with drug-resistant HIV. The goal is to evaluate lenacapavir's effectiveness when added to an ineffective treatment plan. The study includes different groups: some will start with lenacapavir, while others will initially receive a placebo before switching to the actual drug. Individuals with HIV who are on a treatment plan that isn't working well and have limited other treatment options might be suitable for this trial. As a Phase 2, Phase 3 trial, this study assesses lenacapavir's effectiveness in a smaller group and represents the final step before FDA approval, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop your current medications, but it mentions that participants should be on a stable failing regimen for more than 8 weeks. This suggests you may continue your current medications while adding lenacapavir.

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

Research has shown that lenacapavir is generally well-tolerated by people with HIV. When combined with other carefully chosen HIV medications, lenacapavir effectively controlled the virus over two years, and participants managed the treatment well. Studies found no major safety issues. This suggests lenacapavir could be a safe option for those with drug-resistant HIV, though individual experiences may differ. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for HIV?

Lenacapavir is unique because it targets HIV differently than most current treatments. While typical HIV therapies focus on inhibiting viral enzymes like reverse transcriptase or protease, Lenacapavir is a capsid inhibitor, which means it disrupts the HIV virus's protective shell. This novel mechanism can potentially overcome drug resistance issues seen with other treatments. Additionally, Lenacapavir offers a convenient dosing schedule, with the option of subcutaneous injections every six months, reducing the pill burden for patients. Researchers are excited about its potential to enhance treatment for those with drug-resistant HIV, providing a new avenue for managing the condition.

What evidence suggests that lenacapavir could be an effective treatment for drug-resistant HIV?

Research has shown that lenacapavir effectively treats HIV that doesn't respond to other drugs. In this trial, participants in Cohort 1A and Cohort 2 will receive lenacapavir, while those in Cohort 1B will initially receive a placebo before switching to lenacapavir. One study found that 88% of people taking lenacapavir experienced a significant drop in their HIV levels after just 14 days, compared to only 17% of those taking a placebo. Over a longer period, when combined with other HIV treatments, lenacapavir kept the virus under control for up to 104 weeks. This suggests lenacapavir could be a strong option for people with HIV resistant to multiple drugs. ^{1 2 6 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 adults and adolescents living with HIV who have developed resistance to multiple drugs, specifically at least two agents from three or more of the main classes of antiretroviral (ARV) medications. Participants must be on a failing ARV regimen, have an HIV-1 RNA level ≥ 400 copies/mL, and not have an ongoing Hepatitis C infection.

Inclusion Criteria

I have been on the same HIV medication for over 8 weeks without improvement.

I am willing to take lenacapavir with an optimized background regimen.

No Hepatitis C virus (HCV) ongoing infection

Exclusion Criteria

There may be additional criteria set by the study that you need to meet or avoid.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Functional Monotherapy Period

Participants receive oral lenacapavir or placebo while continuing their failing regimen

2 weeks

3 visits (in-person)

Maintenance Period

Participants receive subcutaneous lenacapavir and initiate an optimized background regimen

26 weeks

2 visits (in-person)

Optional Extension

Participants may opt to continue receiving subcutaneous lenacapavir at Weeks 52 and 156

Long-term

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lenacapavir

Trial Overview The study tests Lenacapavir's effectiveness when added to a failing drug regimen in patients with multi-drug resistant HIV. It involves comparing placebo treatments against subcutaneous and oral forms of Lenacapavir alongside an Optimized Background Regimen (OBR).

How Is the Trial Designed?

Group I: Cohort 2: Lenacapavir Experimental Treatment 3 Interventions

Participants with a ≥ 0.5 log10 copies/mL HIV-1 RNA decline at the Cohort Selection Visit compared with the screening visit or with HIV-1 RNA \< 400 copies/mL or if Cohort 1 is fully enrolled will receive oral LEN 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, and will initiate an OBR on Day 1 in Oral Lead-in Period (Baseline to Day 14); followed by Maintenance Period where participants will receive SC LEN 927 mg at Day 1 SC Visit (14 days after the first dose of oral LEN) while continuing their OBR. Participants will receive their subsequent SC LEN injection at Week 26 Visit (relative to Day 1 SC). Participants will be given an option to receive SC LEN injection at Weeks 52 and 156, while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.

Group II: Cohort 1A: Lenacapavir Experimental Treatment 4 Interventions

Participants with HIV-1 ribonucleic acid (RNA) ≥ 400 copies/mL and with a \<0.5 log10 HIV-1 RNA decline at Cohort Selection visit compared with screening visit will receive oral lenacapavir (LEN) 600 mg tablet on Days 1 and 2 and 300 mg tablet on Day 8, while continuing their failing regimen in blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive subcutaneous (SC) LEN 927 mg and will initiate an optimized background regimen (OBR) at Day 1 SC Visit (14 days after the first dose of oral LEN). Participants will receive their subsequent SC LEN injection at Week 26 Visit (relative to Day 1 SC). Participants will be given an option to receive SC LEN injection at Weeks 52 and 156, while continuing their OBR, until product becomes accessible to participants through an access program or until Gilead elects to discontinue the study in the country.

Group III: Cohort 1B: Placebo to Lenacapavir Placebo Group 5 Interventions

Participants with HIV-1 RNA ≥ 400 copies/mL and with a \<0.5 log10 HIV-1 RNA decline at the Cohort Selection visit compared with screening visit will receive oral LEN placebo on Days 1, 2, and 8 while continuing their failing regimen in blinded Functional Monotherapy Period (Baseline to Day 14); followed by unblinded Maintenance Period where participants will receive oral LEN 600 mg on Days 15 and 16 and 300 mg on Day 22, and will initiate an OBR on Day 15. At Day 1 SC (14 days after the first dose of oral LEN), participants will receive SC LEN 927 mg while continuing OBR. Participants will receive their subsequent SC LEN injection at Week 26 Visit (relative to Day 1 SC). Participants will be given an option to receive SC LEN injection at Weeks 52 and 156, while continuing their OBR, until the product becomes accessible to participants through an access program or until Gilead elects to discontinue study in the country.

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 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]

In the CAPELLA study, lenacapavir (LEN) combined with an optimized background regimen (OBR) achieved viral suppression in 81% of heavily treatment-experienced individuals with multidrug-resistant HIV after 26 weeks, demonstrating its efficacy in a challenging patient population.

However, resistance mutations to lenacapavir were observed in 8 participants, indicating that using LEN as an unintended monotherapy can lead to the development of resistance, highlighting the importance of proper treatment adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resistance Analyses in Highly Treatment-Experienced People With Human Immunodeficiency Virus (HIV) Treated With the Novel Capsid HIV Inhibitor Lenacapavir. Margot, NA., Naik, V., VanderVeen, L., et al.[2022]

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]

Citations

1. sunlencahcp.com sunlencahcp.com/efficacy-and-resistance/virologic-outcomes/

SUNLENCA® (lenacapavir) Efficacy Data | HCP Site 88% of participants taking SUNLENCA achieved a ≥0.5 log 10 copies/mL reduction in HIV-1 RNA after 14 days vs 17% of participants taking placebo.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39206943/

Week 104 Results of a Phase 2/3 Trial Treatment with subcutaneous lenacapavir in combination with an OBR was well tolerated and resulted in a high rate of virological suppression over 104 weeks.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12055487/

Lenacapavir for multidrug-resistant HIV-1 infection - PMC Lenacapavir plus an optimised background antiretroviral regimen may be useful for patients with multidrug-resistant HIV-1 infection with inadequate viral ...

4. gilead.com gilead.com/news/news-details/2025/gilead-presents-new-data-on-twice-yearly-lenacapavir-yeztugo-for-hiv-prevention-at-ias-2025

Gilead Presents New Data on Twice Yearly Lenacapavir ... New Data from PURPOSE Trials Further Demonstrate that Lenacapavir (Yeztugo®) was Effective and Well Tolerated Across a Broad Range of ...

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

Clinical Recommendation for the Use of Injectable ... This report describes a clinical recommendation to use injectable lenacapavir as an HIV preexposure prophylaxis.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04150068

NCT04150068 | Study to Evaluate the Safety and Efficacy ... Efficacy and safety of the novel capsid inhibitor lenacapavir to treat multidrug-resistant HIV: week 52 results of a phase 2/3 trial. Lancet HIV. 2023 Aug ...

7. academic.oup.com academic.oup.com/cid/article/80/3/566/7745000

Efficacy and Safety of Long-Acting Subcutaneous Lenacapavir ... In a In a Phase 2/3 study, treatment with lenacapavir, a long-acting HIV-1 capsid inhibitor, plus an optimized background regimen, was well tolerated, with.

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 accumulated data suggests that lenacapavir, like other moderate CYP3A4 inhibitors, can be co-administered with statins and PDE5 inhibitors ...