DOR/ISL for HIV

Not currently recruiting at 117 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme Corp.

Must be taking: Doravirine, Islatravir

Disqualifiers: Pregnancy, Breastfeeding, Prohibited therapies, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 192 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and tolerability of a new HIV treatment, a combination pill called MK-8591A. The pill contains two drugs, doravirine and islatravir, and aims to help people with HIV-1 who have used this treatment in earlier studies. Participants should currently be taking this combination in another study and have experienced benefits from it. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment option.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that you cannot take any prohibited therapies. It's best to discuss your current medications with the trial team to see if they are allowed.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the combination of doravirine and islatravir, known as DOR/ISL, holds promise for treating HIV-1 and is generally safe. Early results from past studies indicate that people tolerate this treatment well. For instance, a study by Merck found that only a few participants discontinued use due to side effects, even over an extended period. Other research has also demonstrated that DOR/ISL performs as well as some current HIV medications, with no major safety issues reported. This suggests that DOR/ISL could be a safe option for people with HIV-1, as previous participants experienced few problems with the medication. ^{1 2 3 4 5}

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

Researchers are excited about MK-8591A for HIV treatment because it combines two innovative ingredients: doravirine and islatravir, in a single tablet. Unlike standard treatments that typically require multiple drugs, this fixed-dose combination simplifies the regimen to just one pill a day, improving adherence. Islatravir, in particular, introduces a novel mechanism by acting as a nucleoside reverse transcriptase translocation inhibitor (NRTTI), which could offer enhanced potency and reduced side effects. This combination aims to provide a more convenient and potentially more effective option for patients managing HIV.

What evidence suggests that this treatment might be an effective treatment for HIV?

Studies have shown that the combination of doravirine and islatravir, known as MK-8591A, effectively treats HIV-1. In one study, 91.5% of participants who switched to this treatment maintained viral suppression. Another study found that within eight days, 85.7% of patients experienced a significant drop in HIV levels, a change not observed in those taking a placebo. Additionally, doravirine/islatravir proved as effective as the commonly used treatment Biktarvy in reducing the virus at Week 48. These results suggest that MK-8591A is a promising option for managing HIV-1. ^{1 2 3 4 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Are You a Good Fit for This Trial?

This trial is for individuals over 35 kg with HIV-1 who are benefiting from the DOR/ISL tablet in a previous MSD study. Participants must not be pregnant or breastfeeding unless local regulations allow and they agree to contraception if of childbearing potential.

Inclusion Criteria

I have benefited from DOR/ISL treatment and my doctor thinks I should continue it.

I am currently taking DOR 100 mg/ISL 0.75 mg tablet from an MSD study and finished my last treatment.

I weigh at least 35 kg and have given my consent.

Exclusion Criteria

Is taking or is anticipated to require any prohibited therapies

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a fixed dose combination tablet of doravirine and islatravir once daily

192 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• MK-8591A

Trial Overview The trial studies MK-8591A, a combination of doravirine (100mg) and islatravir (0.75mg), assessing its safety and tolerability in those previously treated with these drugs for HIV-1.

How Is the Trial Designed?

Group I: MK-8591A Experimental Treatment 1 Intervention

Fixed dose combination (FDC) tablet of 100 mg doravirine, 0.75 mg islatravir taken orally, once daily for up to 192 weeks.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme Corp.

Lead Sponsor

Trials

2,287

Recruited

4,582,000+

Chirfi Guindo

Merck Sharp & Dohme Corp.

Chief Medical Officer

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

Robert M. Davis

Merck Sharp & Dohme Corp.

Chief Executive Officer since 2021

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

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

Published Research Related to This Trial

MK-8591, an investigational drug for HIV treatment, shows promise for long-acting formulations that could improve adherence to treatment regimens, as it maintains effective drug levels for over 6 months after subcutaneous implantation in animal studies.

The drug's active form, MK-8591-TP, demonstrates prolonged intracellular persistence and significant viral load reduction, indicating its potential effectiveness for both treatment and pre-exposure prophylaxis (PrEP) against HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended-Duration MK-8591-Eluting Implant as a Candidate for HIV Treatment and Prevention. Barrett, SE., Teller, RS., Forster, SP., et al.[2020]

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]

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]

Citations

1. merck.com merck.com/news/merck-announces-new-data-from-phase-3-trials-evaluating-the-investigational-once-daily-oral-two-drug-regimen-of-doravirine-islatravir-dor-isl-in-adults-with-virologically-suppressed-hiv-1-infecti/

Merck Announces New Data from Phase 3 Trials ... MK-8591A-052 is a Phase 3, double-blind, randomized, active-controlled clinical trial to evaluate the efficacy and safety of a switch to ...

2. merck.com merck.com/news/merck-announces-positive-data-from-phase-3-trials-that-show-the-investigational-once-daily-oral-two-drug-regimen-of-doravirine-islatravir-dor-isl-maintained-hiv-1-viral-suppression-at-week-48/

Merck Announces Positive Data from Phase 3 Trials that ... At Week 48, 91.5% of participants who switched to DOR/ISL maintained viral suppression (HIV-1 RNA <50 copies/mL) compared to 94.2% of ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/41037024/

Efficacy and safety of doravirine/islatravir in heavily ... From Day 1 to 8, a ≥1.0 log10 decrease in HIV-1 RNA was achieved in 85.7% of the DOR/ISL group compared with 0% of the placebo group. At Week 49 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04233216

NCT04233216 | Doravirine/Islatravir (DOR/ISL) in Heavily ... It is hypothesized that the percentage of participants receiving DOR/ISL to achieve ≥0.5 log10 decrease in HIV-1 ribonucleic acid (RNA) from study baseline (Day ...

5. clinicalinfo.hiv.gov clinicalinfo.hiv.gov/en/drugs/islatravir/patient

Islatravir Patient Drug Record | NIH Selected Study Results: Week 48 results presented at IAS 2023 showed that doravirine/islatravir was as effective as Biktarvy in suppressing viral load in ...

6. academic.oup.com academic.oup.com/cid/article/81/2/322/8074956

Doravirine/Islatravir (100/0.75 mg) Once-Daily Compared With ... Doravirine/islatravir (100/0.75 mg) once-daily was noninferior to bictegravir/emtricitabine/tenofovir alafenamide through week 48 for initial HIV-1 treatment.