Lenacapavir + OBR for Drug-Resistant HIV

(CAPELLA Trial)

Recruiting at 74 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

72 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Lenacapavir for treating drug-resistant HIV?

Lenacapavir, when used with an optimized background regimen, has shown effectiveness in treating people with multidrug-resistant HIV by helping them achieve virologic suppression (reducing the virus to very low levels) and improving their immune system health, as seen in the phase 2/3 CAPELLA study. ^{1 2 3 4 5}

Is Lenacapavir safe for humans?

Lenacapavir has been studied for safety in people with drug-resistant HIV, and results from a phase 2/3 trial up to 52 weeks suggest it is generally safe when used with other HIV medications. However, as with any medication, there may be side effects, and it's important to discuss these with a healthcare provider. ^{1 2 3 4 5}

What makes the drug Lenacapavir unique for treating drug-resistant HIV?

Lenacapavir is unique because it is a first-in-class capsid inhibitor, which means it targets a different part of the HIV virus than other drugs. It is also long-acting, requiring only one injection every six months after an initial oral dose, which can help reduce the daily pill burden for patients with multidrug-resistant HIV. ^{2 3 4 6 7}

What is the purpose of this trial?

The primary objective of this study is to evaluate the antiviral activity of lenacapavir (formerly GS-6207) administered as an add-on to a failing regimen (functional monotherapy) in people with human immunodeficiency virus (HIV) (PWH) with multi-drug resistance (MDR).

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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

Findings from Research

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 (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]

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]

References

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

Indirect Treatment Comparisons of Lenacapavir Plus Optimized Background Regimen Versus Other Treatments for Multidrug-Resistant Human Immunodeficiency Virus. [2023]

2. United States 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

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

4. 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]

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

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

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

Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

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