Islatravir + Lenacapavir for HIV

Recruiting at 47 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Gilead Sciences

Must be taking: B/F/TAF

Must not be taking: Islatravir, Lenacapavir

Disqualifiers: Hepatitis B, Hepatitis C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

142 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests the effectiveness of taking two medications, islatravir and lenacapavir, regularly for people with HIV who already have very low virus levels. The goal is to see if this combination keeps the virus under control over several months.

Will I have to stop taking my current medications?

The trial requires participants to have been on bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for at least 24 weeks before joining. It does not specify if you need to stop other medications, but you must not have used islatravir or lenacapavir before.

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

Islatravir has shown strong antiviral activity and a long-lasting effect in the body, while Lenacapavir, a new type of HIV drug, has demonstrated impressive effectiveness in stopping the virus from multiplying, even in cases where other drugs don't work. Together, these drugs could offer a powerful new option for treating HIV. ^{1 2 3 4 5}

Is the combination of Islatravir and Lenacapavir safe for humans?

Islatravir has been generally well-tolerated in studies with no serious side effects reported, and Lenacapavir is considered a safe and potent antiviral drug with low potential for drug interactions. ^{1 5 6 7 8}

What makes the drug Islatravir + Lenacapavir unique for HIV treatment?

Islatravir + Lenacapavir is unique because it combines two long-acting drugs that target different stages of the HIV life cycle, potentially allowing for less frequent dosing compared to traditional daily HIV medications. ^{9 10 11 12 13}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

This trial is for people with HIV who have maintained a viral load of less than 50 copies/mL and have been on B/F/TAF treatment for at least 24 weeks. They shouldn't have had previous virologic failures, exposure to ISL or LEN, serious infections within the last month, hepatitis B or C co-infections, low kidney function or certain low blood cell counts.

Inclusion Criteria

Plasma HIV-1 RNA < 50 copies/mL at screening

My HIV-1 levels have been undetectable or very low for at least 24 weeks.

I have been on B/F/TAF medication for at least 24 weeks.

Exclusion Criteria

CD4+ T-cells < 200 cells/mm^3 (Cohort 1); CD4+ T-cells < 350 cells/mm^3 (cohort 2)

I have previously used or been exposed to islatravir or lenacapavir.

My kidney function is low, with a creatinine clearance of 30 mL/min or less.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral weekly islatravir in combination with lenacapavir for virologically suppressed people with HIV

48 weeks

Weekly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• B/F/TAF
• Islatravir
• Lenacapavir

Trial Overview The study tests the effectiveness of taking Islatravir (ISL) orally once a week combined with Lenacapavir (LEN) in those whose HIV is already under control. The goal is to see how well this combination works after 24 weeks compared to their current treatment.

Participant Groups

Group I: Cohort 2 (ISL+LEN) Experimental Treatment 2 Interventions

Participants will receive the following for at least 48 weeks * Day 1: LEN oral 600 mg (2 x 300 mg) and ISL 2 mg (2 x 1 mg) * Day 2: LEN only oral 600 mg (2 x 300 mg) * Day 8 and weekly thereafter (ie, every 7 days): LEN oral 300 mg (1 x 300 mg) and ISL 2 mg

Group II: Cohort 2 (B/F/TAF to ISL+LEN) Experimental Treatment 3 Interventions

Participants will receive B/F/TAF 50/200/25 mg once daily for at least 48 weeks After 48 weeks, participants will switch from B/F/TAF to ISL+LEN * Day 1: LEN oral 600 mg (2 x 300 mg) and ISL 2 mg (2 x 1 mg) * Day 2: LEN only oral 600 mg (2 x 300 mg) * Day 8 and weekly thereafter (ie, every 7 days): LEN oral 300 mg (1 x 300 mg) and ISL 2 mg Participants who do not switch from B/F/TAF to ISL+LEN at Week 48 will be discontinued from the study.

Group III: Cohort 1 (ISL+LEN) Experimental Treatment 2 Interventions

Participants will receive the following for at least 48 weeks: * Day 1 and Day 2: ISL 40 and LEN 600 mg * Day 8 and weekly thereafter (ie, every 7 days): ISL 20 mg and LEN 300 mg

Group IV: Cohort 1 (B/F/TAF to ISL+LEN) Experimental Treatment 3 Interventions

Participants will receive bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) 50/200/25 mg once daily for at least 48 weeks After 48 weeks, participants will switch from B/F/TAF to ISL+LEN * ISL 40 and LEN 600 mg on Day 1 and Day 2 * ISL 20 mg and LEN 300 mg weekly Participants who do not switch from B/F/TAF to ISL+LEN at Week 48 will be discontinued from the study.

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

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

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 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]

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]

A phase-I clinical trial involving 48 healthy Chinese subjects demonstrated that the generic version of sunitinib is bioequivalent to the original Sutent®, with pharmacokinetic parameters falling within the acceptable range for bioequivalence.

Both sunitinib and Sutent® exhibited comparable safety profiles, supporting the use of generic sunitinib as a viable alternative treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of sunitinib and Sutent&#174; in Chinese healthy subjects: an open-label, randomized, crossover study. Wang, Y., Deng, Q., Gao, Z., et al.[2023]

References

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

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

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

Lenacapavir: A Novel Long-Acting Capsid Inhibitor for HIV. [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. 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. Italy pubmed.ncbi.nlm.nih.gov

Pharmacological outlook of Lenacapavir: a novel first-in-class Long-Acting HIV-1 Capsid Inhibitor. [2023]

6. France pubmed.ncbi.nlm.nih.gov

Cobicistat + elvitegravir + emtricitabine + tenofovir. Two new drugs, but no progress. [2021]

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

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

8. 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]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of sunitinib and Sutent&#174; in Chinese healthy subjects: an open-label, randomized, crossover study. [2023]

10. England pubmed.ncbi.nlm.nih.gov

A phase I/II study of lenalidomide in combination with sunitinib in patients with advanced or metastatic renal cell carcinoma. [2023]

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

Long-term response with sunitinib for metastatic renal cell carcinoma. [2018]

12. Germany pubmed.ncbi.nlm.nih.gov

Sunitinib DDI with paracetamol, diclofenac, mefenamic acid and ibuprofen shows sex-divergent effects on the tissue uptake and distribution pattern of sunitinib in mice. [2018]

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

Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. [2022]