ISL + ULO for HIV

Recruiting at 20 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme LLC

Must be taking: BIC/FTC/TAF

Must not be taking: Islatravir, Ulonivirine

Disqualifiers: HIV-2, Active AIDS, HCV, HBV, 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

150 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 requires that you have been on the BIC/FTC/TAF treatment with controlled HIV-1 levels for at least 6 months before joining.

What data supports the effectiveness of the drug Islatravir for HIV treatment?

Research shows that Islatravir has strong antiviral activity and a long-lasting effect in the body, making it promising for treating HIV-1. It has been tested in people with HIV and shown to be effective in reducing the virus. ^{1 2 3 4 5}

What safety data exists for Islatravir (ISL) in humans?

Islatravir has been studied for safety in adults with and without HIV, showing it is generally safe when used alone or with other medications for HIV treatment. These studies have not reported major safety concerns, but they are ongoing to ensure its safety profile remains acceptable. ^{2 3 4 5 6}

What makes the ISL + ULO drug unique for treating HIV?

The ISL + ULO drug is unique because it includes islatravir, a novel nucleoside reverse transcriptase translocation inhibitor, which has a long-lasting effect and can be used for both treatment and prevention of HIV-1. This combination may offer a new approach compared to existing treatments by potentially reducing the frequency of dosing due to islatravir's long half-life. ^{1 2 3 4 6}

What is the purpose of this trial?

Investigators are trying to find better treatments for people with HIV-1. In this clinical study, investigators want to see how well a new treatment called ISL+ULO, taken once a week, works compared to an existing treatment called BIC/FTC/TAF, which is taken every day. Investigators will check how many people still have a high level of the virus in their blood after 24 weeks. The investigators also want to understand if the new treatment, MK-8591B, is safe and how well people can handle it.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

This trial is for adults with HIV-1 who have been successfully treated and virus-suppressed using BIC/FTC/TAF therapy for at least 6 months without any past treatment failures. Participants must have maintained a viral load under 50 copies/mL to qualify.

Inclusion Criteria

The main

I've been on BIC/FTC/TAF for HIV with successful control for over 6 months without past treatment failures.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive either ISL + ULO once weekly or BIC/FTC/TAF once daily for 48 weeks

48 weeks

Treatment Part 2

Participants continue or switch to ISL + ULO once weekly for an additional 48 weeks

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Islatravir
• Ulonivirine

Trial Overview The study compares a new once-weekly HIV-1 treatment regimen (ISL+ULO) against the standard daily regimen (BIC/FTC/TAF). The goal is to see if ISL+ULO maintains virus suppression after 24 weeks and assess its safety and tolerability.

Participant Groups

Group I: ISL + ULO in Group 2 Experimental Treatment 2 Interventions

In part 2 of the study, participants previously on BIC/FTC/TAF (for the 1st 48 weeks, or part 1) will switch to ISL + ULO, to week 96.

Group II: ISL + ULO in Group 1 Experimental Treatment 2 Interventions

In part 1 of the study, participants will receive ISL 2mg + ULO 200mg orally once a week (QW) for 48 weeks. In part 2 (2nd 48 weeks), participants will continue to receive ISL 2mg + ULO 200mg once a week till week 96.

Group III: BIC/FTC/TAF in Group 2 Active Control 1 Intervention

In part 1 of the study, participants will receive BIC 50mg/FTC 200mg/TAF 25mg orally once daily (QD) for 48 weeks.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead 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 (ISL) is a novel long-acting reverse transcriptase translocation inhibitor that has shown strong antiviral activity in both daily and weekly dosing regimens for HIV-1 treatment, achieving high levels of virologic suppression in clinical trials.

In preclinical studies, ISL demonstrated effectiveness as a once-weekly pre-exposure prophylaxis (PrEP) against SHIV infection in rhesus macaques, and recent data suggest the potential for a once-yearly implantable formulation for HIV-1 prevention in healthy individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Islatravir for the treatment and prevention of infection with the human immunodeficiency virus type 1. Markowitz, M., Grobler, JA.[2021]

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]

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

Islatravir for the treatment and prevention of infection with the human immunodeficiency virus type 1. [2021]

2. 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]

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

Role of islatravir in HIV treatment and prevention: an update. [2022]

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

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

5. Netherlands pubmed.ncbi.nlm.nih.gov

Islatravir in combination with doravirine for treatment-naive adults with HIV-1 infection receiving initial treatment with islatravir, doravirine, and lamivudine: a phase 2b, randomised, double-blind, dose-ranging trial. [2021]

6. 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]