Islatravir + Lenacapavir for HIV

(ISLEND-1 Trial)

Recruiting at 111 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Gilead Sciences

Must be taking: B/F/TAF

Must not be taking: ISL, LEN

Disqualifiers: Virologic failure, Active infections, Hepatitis B, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

The goal of this clinical study is to learn about the safety and efficacy of switching to once weekly tablet of islatravir/lenacapavir (ISL/LEN) regimen versus continuing standard treatment of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with human immunodeficiency virus (PWH) who are virologically suppressed (HIV-1 RNA levels \< 50 copies/mL) on B/F/TAF for ≥ 6 months prior to screening. The primary objective is to evaluate the efficacy of switching to oral weekly ISL/LEN tablet regimen versus continuing B/F/TAF in virologically suppressed PWH at Week 48.

Will I have to stop taking my current medications?

The trial requires participants to switch from their current HIV medication (B/F/TAF) to the new study medication (ISL/LEN) if they choose to participate. You will need to stop taking B/F/TAF and start the new regimen.

What data supports the effectiveness of the drug Islatravir/Lenacapavir for HIV?

Islatravir has shown potent antiviral activity and a long-lasting effect in people with HIV, while Lenacapavir is effective against drug-resistant HIV and works well with other HIV drugs. Together, they may offer a strong treatment option for HIV. ^{1 2 3 4 5}

What makes the drug Islatravir/Lenacapavir unique for treating HIV?

Islatravir/Lenacapavir is unique because it combines two novel components: Islatravir, which has a long-lasting effect inside cells, and Lenacapavir, which is designed for long-acting use, potentially allowing for less frequent dosing compared to traditional HIV treatments. ^{1 2 6 7 8}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

This trial is for people with HIV who have had low virus levels (<50 copies/mL) for at least 6 months while on B/F/TAF treatment. They must be willing to continue their current treatment until the start of the study and, if they can become pregnant, agree to use certain birth control methods.

Inclusion Criteria

Key

My HIV viral load is under 50 copies/mL.

I have been on B/F/TAF for at least 6 months and can continue it.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Blinded Phase

Participants receive either ISL/LEN with PTM B/F/TAF or PTM ISL/LEN with B/F/TAF for 96 weeks

96 weeks

Open-label Extension

Participants may opt into continuation of ISL/LEN treatment until it becomes available or the study is discontinued

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Islatravir/Lenacapavir (Virus Therapy)

Trial Overview The study compares a once-weekly oral tablet regimen of islatravir/lenacapavir (ISL/LEN) against continuing the standard daily bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF). The main goal is to see if switching treatments maintains low HIV levels after 48 weeks.

Participant Groups

Group I: Open- Label Extension (OLE) Phase Experimental Treatment 1 Intervention

After the end of Blinded Phase at Week 96, if safety and efficacy of ISL/LEN are demonstrated following review of unblinded data, all participants will be given an option to enter the open-label extension phase to receive ISL/LEN in an extension phase until ISL/LEN becomes available or until the sponsor elects to discontinue the study, whichever occurs first. Participants receiving ISL/LEN and PTM B/F/TAF during the blinded phase will continue to take ISL/LEN weekly. Participants receiving B/F/TAF and PTM ISL/LEN during the blinded phase will take an initial dose of ISL/LEN (Dose A), followed by once weekly ISL/LEN (Dose B) from Day 8 onwards.

Group II: Blinded Phase: PTM ISL/LEN + B/F/TAF Experimental Treatment 2 Interventions

Participants will receive an initial dose of PTM ISL/LEN (Dose A), followed by once weekly PTM ISL/LEN (Dose B) from Day 8 onwards up to Week 96. Participants will also receive B/F/TAF (50/200/25 mg) once daily up from Day 1 up to Week 96.

Group III: Blinded Phase: ISL/LEN + Placebo-to-Match (PTM) B/F/TAF Experimental Treatment 2 Interventions

Participants will receive an initial dose of ISL/LEN (Dose A), followed by once weekly ISL/LEN (Dose B) from Day 8 onwards up to Week 96. Participants will also receive PTM B/F/TAF once daily from Day 1 up to Week 96.

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

Islatravir, a new treatment for HIV-1, was found to be generally well tolerated in a phase 1b trial with 30 treatment-naive adults, showing that it can significantly reduce HIV-1 RNA levels by more than 1.0 log after just 7 days, even at low doses of 0.5 mg.

The study demonstrated that islatravir has a long intracellular half-life of 78.5-128.0 hours, which may contribute to its prolonged effects against the virus, and no serious adverse events or signs of viral resistance were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and antiretroviral activity of islatravir (ISL, MK-8591), a novel nucleoside reverse transcriptase translocation inhibitor, following single-dose administration to treatment-naive adults infected with HIV-1: an open-label, phase 1b, consecutive-panel trial. Schürmann, D., Rudd, DJ., Zhang, S., et al.[2020]

Islatravir, a novel nucleoside analog for HIV treatment and prevention, demonstrated potent antiviral activity with a long intracellular half-life, achieving therapeutic concentrations in both plasma and tissue after daily administration for up to 6 weeks.

The study involving 36 adults showed that islatravir was generally well tolerated at doses up to 5 mg, with effective levels of its active form (ISL-TP) reached after just one dose, indicating its potential for effective HIV treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Pharmacokinetics of Once-Daily Multiple-Dose Administration of Islatravir in Adults Without HIV. Matthews, RP., Jackson Rudd, D., Zhang, S., et al.[2023]

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 (LEN) is the first HIV-1 capsid inhibitor approved for multidrug-resistant HIV-1 infection, showing efficacy with a low level of drug-related mutations and no cross-resistance to other anti-HIV drugs.

LEN can be administered as a long-acting treatment, making it suitable for patients with limited access to healthcare, and it has demonstrated potential for synergistic effects when combined with other anti-HIV medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Highlights on the Development, Related Patents, and Prospects of Lenacapavir: The First-in-Class HIV-1 Capsid Inhibitor for the Treatment of Multi-Drug-Resistant HIV-1 Infection. Dzinamarira, T., Almehmadi, M., Alsaiari, AA., 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]

In a study involving 24 adult participants, the coadministration of islatravir and doravirine did not significantly affect the pharmacokinetics of either drug, indicating that they can be safely combined without altering their effectiveness.

All treatment regimens were well tolerated, suggesting that islatravir and doravirine can be further investigated together for the treatment of HIV-1 infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase 1 Study to Evaluate the Drug Interaction Between Islatravir (MK-8591) and Doravirine in Adults Without HIV. Matthews, RP., Jackson Rudd, D., Fillgrove, KL., et al.[2021]

Islatravir (MK-8591) was found to be generally well-tolerated in two Phase 1 trials involving 32 participants, with no serious adverse events reported, indicating a favorable safety profile for this potential HIV treatment.

The pharmacokinetics of islatravir showed rapid absorption and a long half-life, with intracellular levels of its active form comparable to those associated with efficacy in preclinical studies, supporting its potential effectiveness in treating and preventing HIV-1.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and pharmacokinetics of single- and multiple-dose administration of islatravir (MK-8591) in adults without HIV. Matthews, RP., Ankrom, W., Friedman, E., et al.[2022]

In a phase 2b trial involving 121 treatment-naive participants, islatravir combined with doravirine maintained HIV-1 RNA levels below 50 copies per milliliter in 81.1% of participants over 96 weeks, demonstrating its efficacy in viral suppression.

The safety profile of islatravir was favorable, with only 7.8% of participants experiencing drug-related adverse events, compared to 22.6% in the DOR/3TC/TDF group, indicating better tolerability for the islatravir regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brief Report: Efficacy and Safety of Oral Islatravir Once Daily in Combination With Doravirine Through 96 Weeks for Treatment-Naive Adults With HIV-1 Infection Receiving Initial Treatment With Islatravir, Doravirine, and Lamivudine. Molina, JM., Yazdanpanah, Y., Afani Saud, A., et al.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Safety, pharmacokinetics, and antiretroviral activity of islatravir (ISL, MK-8591), a novel nucleoside reverse transcriptase translocation inhibitor, following single-dose administration to treatment-naive adults infected with HIV-1: an open-label, phase 1b, consecutive-panel trial. [2020]

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

Safety and Pharmacokinetics of Once-Daily Multiple-Dose Administration of Islatravir in Adults Without HIV. [2023]

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

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

4. Switzerland pubmed.ncbi.nlm.nih.gov

Highlights on the Development, Related Patents, and Prospects of Lenacapavir: The First-in-Class HIV-1 Capsid Inhibitor for the Treatment of Multi-Drug-Resistant HIV-1 Infection. [2023]

5. 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]

6. New Zealand pubmed.ncbi.nlm.nih.gov

A Phase 1 Study to Evaluate the Drug Interaction Between Islatravir (MK-8591) and Doravirine in Adults Without HIV. [2021]

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

Safety, tolerability, and pharmacokinetics of single- and multiple-dose administration of islatravir (MK-8591) in adults without HIV. [2022]

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

Brief Report: Efficacy and Safety of Oral Islatravir Once Daily in Combination With Doravirine Through 96 Weeks for Treatment-Naive Adults With HIV-1 Infection Receiving Initial Treatment With Islatravir, Doravirine, and Lamivudine. [2023]