DOR/ISL for HIV

Not currently recruiting at 153 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Disqualifiers: HIV-2, Active hepatitis B, Cirrhosis, 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: 144 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for individuals with HIV-1 who have not yet started antiretroviral therapy. The study compares the effectiveness, safety, and tolerability of a new drug combination, doravirine/islatravir (DOR/ISL), with an existing treatment. Participants will receive either DOR/ISL or the standard treatment and will take part in the study for 144 weeks. Ideal candidates for this trial are those who have tested positive for HIV-1, have a certain level of the virus in their blood, and have not taken any HIV medication. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in HIV treatment.

Do I have to stop taking my current medications for the trial?

The trial is for people who have never taken HIV medications before, so if you are already on HIV treatment, you would not be eligible. The protocol does not specify if you need to stop other non-HIV medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the treatment combination of doravirine and islatravir (DOR/ISL) is generally well-tolerated by people with HIV-1. Previous studies found that participants experienced only small changes in weight and body composition, with no major effects on fasting lipids, which are fats in the blood. Another study found that DOR/ISL helped control the HIV virus and was mostly well-tolerated by participants. Although some individuals experienced virologic failure, they still maintained low levels of HIV in their blood. Overall, these findings suggest the treatment is safe for humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard HIV treatments that often combine several medications, DOR/ISL offers a simplified regimen by combining two key drugs, doravirine (DOR) and islatravir (ISL), into a single daily pill. Researchers are excited because this combination targets HIV with a unique approach: DOR is a non-nucleoside reverse transcriptase inhibitor (NNRTI), while ISL introduces a new mechanism as a nucleoside reverse transcriptase translocation inhibitor (NRTTI). This innovative dual-action may improve efficacy and reduce side effects compared to traditional regimens, which often require more pills and complex dosing schedules.

What evidence suggests that this trial's treatments could be effective for HIV?

Research has shown that the combination of doravirine and islatravir (DOR/ISL), which participants in this trial may receive, holds promise for treating HIV-1. One study found that 85.7% of patients taking DOR/ISL experienced a significant drop in HIV-1 levels within just a week, while the placebo group showed no such change. Another study found that DOR/ISL was as effective as the standard treatment, bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), in controlling the virus over 48 weeks. The treatment caused minimal weight changes and did not significantly affect cholesterol levels. Overall, DOR/ISL shows strong potential for effectively managing HIV-1. ^{1 2 3 5 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 adults with HIV-1 who haven't had any antiretroviral therapy. Women must not be pregnant, breastfeeding, or if capable of childbearing, agree to use contraception. Participants need a viral load over 500 copies/mL but can't join if they have HIV-2, recent AIDS-related infections, active hepatitis B or C with cirrhosis signs, certain cancers within the last 5 years, or conditions that might skew results.

Inclusion Criteria

Is HIV-1 positive with plasma HIV-1 RNA ≥500 copies/mL at screening

I am not pregnant, breastfeeding, and willing to use birth control or abstain from sex if I can have children.

I have never taken HIV medication since my diagnosis.

Exclusion Criteria

Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator

I was diagnosed with a serious infection related to AIDS within the last month.

Has a history or current evidence of any condition (including active tuberculosis infection), therapy, laboratory abnormality, or other circumstance (including drug or alcohol use or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive DOR/ISL or BIC/FTC/TAF once daily for 144 weeks

144 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BIC
• DOR
• FTC
• ISL
• TAF

Trial Overview

The study compares two HIV treatments: DOR/ISL and BIC/FTC/TAF. It's randomized and double-blind meaning participants are put into groups by chance without knowing which treatment they get. The goal is to see if DOR/ISL works as well as BIC/FTC/TAF in reducing the virus to undetectable levels after 48 weeks.

How Is the Trial Designed?

Group I: DOR/ISL Experimental Treatment 2 Interventions

Participants take DOR/ISL and placebo to BIC/FTC/TAF once daily (qd) for 144 weeks.

Group II: BIC/FTC/TAF Active Control 2 Interventions

Participants take BIC/FTC/TAF and placebo to DOR/ISL qd for 144 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

Published Research Related to This Trial

In a study of 147 people living with HIV-1, including 93 individuals over 55 years old, the once-daily regimen of bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) demonstrated significant efficacy, with an increase in HIV-RNA suppression and CD4+ T cell counts after 48 weeks.

The treatment was found to be safe and well-tolerated, with no adverse events or discontinuations reported, and it also improved lipid profiles while maintaining healthy ranges for weight and BMI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Switching to a Bictegravir Single Tablet Regimen in Elderly People Living with HIV-1: Data Analysis from the BICTEL Cohort. Lazzaro, A., Cacciola, EG., Borrazzo, C., et al.[2022]

Bictegravir (BIC) combined with emtricitabine (FTC) and tenofovir alafenamide (TAF) in the fixed-dose regimen Biktarvy® has been shown to be as effective as other leading HIV treatments, making it a strong option for initial and long-term therapy.

Biktarvy® has a high barrier to drug resistance and limited drug-drug interactions, which enhances its safety profile and makes it a recommended choice in recent HIV treatment guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biktarvy for the treatment of HIV infection: Progress and prospects. De Clercq, E., Zhang, Z., Huang, J., et al.[2023]

Bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) is an effective and well-tolerated treatment for people living with HIV, showing low rates of virologic failure after 96 weeks in a cohort of 164 participants, including 106 individuals over 55 years old.

The treatment led to significant improvements in CD4+ T cell counts and CD4+/CD8+ ratios without negatively impacting metabolic health, although some worsening of renal function was noted, indicating the need for ongoing monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune Reconstitution and Safe Metabolic Profile after the Switch to Bictegravir/Emtricitabine/Tenofovir Alafenamide Fumarate among Virologically Controlled PLWH: A 96 Week Update from the BICTEL Cohort. Lazzaro, A., Bianchini, D., Gentilini Cacciola, E., 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 ...

DOR/ISL data presented show minimal changes in weight and body composition and no clinically meaningful effect on fasting lipids and the ...

2.

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 ...

3.

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 ...

4.

clinicalinfo.hiv.gov

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

Islatravir Patient Drug Record | NIH

Selected Study Results: Results published in Lancet HIV (2021) showed that treatment regimens containing islatravir and doravirine were highly effective in ...

5.

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.

6.

clinicalinfo.hiv.gov

clinicalinfo.hiv.gov/en/drugs/islatravir/health-professional

Islatravir Health Professional Drug Record | NIH

By Week 48, five participants who received ISL plus DOR had experienced protocol-defined virologic failure; however, all of these participants had HIV-1 RNA <80 ...