DOR/ISL for HIV

Recruiting at 98 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

2000 Participants Needed

Trial Summary

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.

What makes the drug DOR/ISL unique for treating HIV?

DOR/ISL is unique because it combines doravirine, which is a non-nucleoside reverse transcriptase inhibitor, with islatravir, a novel nucleoside reverse transcriptase translocation inhibitor. This combination creates a high barrier to resistance, meaning it's harder for the virus to become resistant to the treatment, compared to other drug combinations. ^{1 2 3 4 5}

What is the purpose of this trial?

The safety and tolerability of MK-8591A, a 2-drug fixed dose combination (FDC) of doravirine (DOR 100mg) and islatravir (ISL 0.75mg) will be evaluated in participants with Human Immunodeficiency Virus -1 (HIV-1) who were treated with DOR and ISL in earlier clinical studies.

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

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]

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]

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

Doravirine and Islatravir Have Complementary Resistance Profiles and Create a Combination with a High Barrier to Resistance. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

HIV-1 Resistance to Islatravir/Tenofovir Combination Therapy in Wild-Type or NRTI-Resistant Strains of Diverse HIV-1 Subtypes. [2023]

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

Extended-Duration MK-8591-Eluting Implant as a Candidate for HIV Treatment and Prevention. [2020]

5. 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]