DOR/ISL for HIV/AIDS

No longer recruiting at 102 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must be taking: BIC/FTC/TAF

Must not be taking: Immunosuppressives, Immune modulators

Disqualifiers: HIV-2, Hepatitis, Recent malignancy, 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 explores a new treatment option for individuals with HIV-1 who are on a stable regimen and have their viral load under control. It compares the effectiveness and safety of switching to a new combination pill, doravirine and islatravir (DOR/ISL), against continuing the current treatment. The main goal is to determine if the new combination is equally effective at keeping the virus suppressed. Candidates may qualify if they have been on a regimen of bictegravir, emtricitabine, and tenofovir alafenamide with successful viral suppression for at least three months. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Do I need to stop my current medications for this trial?

Yes, you will need to stop your current medications. The trial involves switching from your current HIV treatment (BIC/FTC/TAF) to a new combination (MK-8591A).

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

Research has shown that the combination of doravirine and islatravir (DOR/ISL) is generally well-tolerated by people with HIV-1. In earlier studies, most participants experienced only minor changes in weight and body shape. Additionally, there were no major changes in blood fats, suggesting that the treatment does not cause significant side effects impacting overall health.

Another study found that switching to DOR/ISL controlled the virus as effectively as other treatments. This indicates the treatment's effectiveness without causing additional harm.

Overall, evidence from these studies suggests that DOR/ISL is safe, with few negative effects reported. This information may reassure those considering participation in a trial with these medications. ^{1 2 3 4 5}

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

Researchers are excited about the DOR/ISL treatment for HIV/AIDS because it offers a new fixed-dose combination of doravirine and islatravir. Unlike many standard treatments, which typically involve multiple pills and regimens, DOR/ISL simplifies the process into a single pill. Doravirine is a modern non-nucleoside reverse transcriptase inhibitor (NNRTI) known for fewer side effects, while islatravir introduces a novel mechanism as a nucleoside reverse transcriptase translocation inhibitor (NRTTI), potentially enhancing effectiveness by working differently than other drugs. This combination offers a promising new approach to HIV treatment by potentially improving adherence and efficacy.

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

Research has shown that doravirine/islatravir (DOR/ISL), one of the treatments in this trial, effectively treats HIV-1. Studies have found that DOR/ISL performs as well as the common treatment bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), another option in this trial, in reducing the virus in the body. One study revealed that 85.7% of participants taking DOR/ISL experienced a significant drop in their HIV-1 levels within the first week, while none in the control group did. Over 96 weeks, DOR/ISL continued to perform well against the virus and remained safe to use. This suggests that DOR/ISL could be a strong option for managing HIV-1 effectively. ^{2 4 5 6 7}

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 HIV-1 positive adults with a stable viral load under 50 copies/mL on BIC/FTC/TAF therapy for at least 3 months, without past treatment failure. Women must not be pregnant or breastfeeding and either not of childbearing potential or using contraception. Exclusions include recent participation in other studies, resistance to DOR, intent to conceive, HIV-2 infection, active hepatitis or certain cancers within the last 5 years.

Inclusion Criteria

I've been on BIC/FTC/TAF for HIV with successful results for over 3 months and never failed any HIV treatments.

I am not pregnant or breastfeeding, and I either cannot become pregnant, am using birth control, or am not having sex.

Is HIV-1 positive with plasma Human Immunodeficiency Virus 1 (HIV-1) RNA <50 copies/mL at screening.

Exclusion Criteria

Is currently participating in or has participated in a clinical study with an investigational compound or device from 45 days prior to Day 1 through the study treatment period.

I haven't had cancer in the last 5 years, except for certain skin cancers or in situ cervical cancer.

Female expects to conceive or donate eggs at any time during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

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

144 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants who benefit from their assigned intervention can continue treatment for an additional 24 weeks

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bictegravir/Emtricitabine/Tenofovir Alafenamide
• Doravirine/Islatravir

Trial Overview

The study tests if switching from BIC/FTC/TAF to a new drug combo (Doravirine/Islatravir) maintains low HIV levels. Participants are randomly assigned to continue their current meds or switch to the new one. The main goal is seeing if the new combo works just as well by checking virus levels after 48 weeks.

How Is the Trial Designed?

Group I: DOR/ISL Experimental Treatment 2 Interventions

A fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) for 144 weeks; and placebo to Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) for 96 weeks.

Group II: BIC/FTC/TAF Active Control 3 Interventions

50 mg bictegravir (BIC), 200 mg emtricitabine (FTC), 25 mg tenofovir alafenamide (TAF) for 144 weeks, and placebo to FDC DOR/ISL for 96 weeks. Participants will be offered the option to receive open-label FDC DOR/ISL from Week 144 to Week 156.

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

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

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.

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 ...

3.

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.

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9377497/

Brief Report: Efficacy and Safety of Oral Islatravir Once ...

The 96-week results of this phase 2b trial further illustrate that islatravir plus doravirine has high antiviral efficacy and a favorable safety profile.

5.

journals.lww.com

journals.lww.com/aidsonline/abstract/9900/efficacy_and_safety_of_doravirine_islatravir_in.792.aspx

Efficacy and safety of doravirine/islatravir in heavily... : AIDS

From Day 1 to 8, a ≥1.0 log 10 decrease in HIV-1 RNA was achieved in 85.7% of the DOR/ISL group compared with 0% of the placebo group. At Week ...

6.

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 ...

7.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/38734015/

Switch to fixed-dose doravirine (100 mg) with islatravir (0· ...

Switching to single-tablet doravirine (100 mg) and islatravir (0·75 mg) maintained viral suppression up to week 48 and was non-inferior to antiretroviral ...