DOR/ISL for HIV

Not currently recruiting at 58 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Antiretrovirals

Must not be taking: Immunosuppressants, CYP3A inducers

Disqualifiers: HIV-2, Active AIDS, Hepatitis B, 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 HIV treatment called Doravirine/Islatravir (DOR/ISL) to determine its effectiveness and safety compared to the current standard antiretroviral therapy (ART). Participants will either switch to DOR/ISL or continue their usual ART, with results compared over 48 weeks. It suits individuals with HIV-1 who have maintained viral control with their current ART for at least three months. The goal is to ensure the new treatment works effectively without increasing the virus in the blood. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to the development of a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial involves switching from your current HIV medication to Doravirine/Islatravir (DOR/ISL). You will need to stop your current antiretroviral therapy to participate in this study.

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

Research has shown that the treatment combination of Doravirine and Islatravir (DOR/ISL) is generally well-tolerated. Studies have found that this combination effectively controls the HIV virus and is safe to use. It causes only minor changes in weight and body shape and does not significantly affect cholesterol or other blood fats.

Additionally, participants taking DOR/ISL have not reported serious side effects. The treatment performs as well as other common HIV treatments for up to 48 weeks. These findings suggest that DOR/ISL is a safe option for those considering joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for HIV?

Researchers are excited about Doravirine/Islatravir (DOR/ISL) because it combines unique features that set it apart from current HIV treatments. Most existing options require multiple drugs for effective viral suppression, but DOR/ISL simplifies this by combining two active ingredients in one treatment. Doravirine is a non-nucleoside reverse transcriptase inhibitor, while Islatravir is a novel nucleoside reverse transcriptase translocation inhibitor, offering a new mechanism of action that enhances the efficacy against HIV-1. This combination not only streamlines the treatment regimen but also has the potential to maintain viral suppression with less frequent dosing, which could improve adherence and quality of life for people living with HIV.

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

Research has shown that Doravirine/Islatravir (DOR/ISL) effectively treats HIV-1. Studies found DOR/ISL to be as effective as other treatments, such as Biktarvy, in controlling the virus, with similar success in reducing it to low levels. At Week 48, only a small number of participants had high virus levels, comparable to other leading treatments. Additionally, over 85% of patients experienced a significant drop in virus levels within just one week of starting DOR/ISL. This trial will test DOR/ISL in two different treatment arms: one where participants receive ART followed by DOR/ISL, and another where participants receive DOR/ISL alone. These findings suggest that DOR/ISL could be a strong option for controlling the virus in people with HIV. ^{1 3 4 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 are successfully managing their virus levels (below 50 copies/mL) on current ART regimens without any history of treatment failure. Women must either not be able to bear children or use reliable contraception and have a negative pregnancy test.

Inclusion Criteria

Is HIV-1 positive with plasma HIV-1 RNA <50 copies/mL at screening

I have been on a stable HIV treatment for over 3 months with no past treatment failures.

I am not able to have children, or I use birth control or do not have penile-vaginal sex, and I have a negative pregnancy test.

Exclusion Criteria

I am infected with HIV-2.

I have an active hepatitis B infection.

I have taken long-acting HIV therapy before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are treated with standard of care ART for 48 weeks, followed by 96 weeks of treatment with DOR/ISL

144 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment with DOR/ISL for up to an additional 96 weeks or until DOR/ISL is commercially accessible

Up to 96 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ART
• Doravirine/Islatravir

Trial Overview The study compares the safety and effectiveness of switching to Doravirine/Islatravir (DOR/ISL) versus continuing with existing ART at keeping HIV-1 RNA below detectable levels after 48 weeks, aiming to prove DOR/ISL is just as good.

How Is the Trial Designed?

Group I: DOR/ISL Experimental Treatment 1 Intervention

Participants with Human Immunodeficiency Virus-1 (HIV-1) that have been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline antiretroviral therapy (ART) receive doravine/islatravir (DOR/ISL), a fixed dose combination (FDC) of 100 mg DOR/0.25 mg ISL orally once daily (qd) for 144 weeks. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).

Group II: ART + DOR/ISL Active Control 2 Interventions

Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months who were previously treated with continuous baseline ART received standard of care (SOC) ART for 48 weeks, followed by treatment with DOR/ISL as a FDC of 100 mg DOR/0.25 mg ISL orally qd until Week 144. At Week 144, participants who consent to enter the optional study extension will continue to receive DOR/ISL qd (100 mg/0.25 mg) for an additional 96 weeks or until it is commercially accessible (whichever comes first).

ART is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Antiretroviral Therapy for:

• HIV-1 infection
• HIV-2 infection

Approved in United States as Antiretroviral Therapy for:

• HIV-1 infection
• HIV-2 infection

Approved in Canada as Antiretroviral Therapy for:

• HIV-1 infection
• HIV-2 infection

Approved in Japan as Antiretroviral Therapy for:

• HIV-1 infection
• HIV-2 infection

Approved in China as Antiretroviral Therapy for:

• HIV-1 infection
• HIV-2 infection

Approved in Switzerland as Antiretroviral Therapy for:

• HIV-1 infection
• HIV-2 infection

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

Combination antiretroviral therapy (cART) is becoming increasingly effective due to the development of new antiretroviral agents and treatment regimens.

Despite these advancements, the long-term success of HIV/AIDS treatment is at risk due to the emergence of drug-resistant strains that can resist multiple agents and entire drug classes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Basis of selection of first and second line highly active antiretroviral therapy for HIV/AIDS on genetic barrier to resistance: a literature review. Katusiime, C., Ocama, P., Kambugu, A.[2021]

Novel antiretroviral agents, such as capsid inhibitors and second-generation maturation inhibitors, show high potency and potential for extended-duration dosing, which could improve treatment adherence for people living with HIV.

Islatravir, a nucleoside reverse transcriptase translocation inhibitor, has demonstrated sustained drug levels in a phase I trial, while fostemsavir is now available for compassionate use in patients with multi-drug-resistant HIV, highlighting advancements in treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Antiretroviral Agents. Cambou, MC., Landovitz, RJ.[2021]

Antiretroviral therapy (ART) is now recommended for all patients with HIV-1, with treatment strategies tailored based on factors like CD4+ T-lymphocyte count and presence of opportunistic infections, aiming to achieve an undetectable plasma viral load.

Initial ART should consist of three drugs, including two nucleoside reverse transcriptase inhibitors (NRTIs) and one additional drug, with integrase strand transfer inhibitors (INSTIs) being preferred for their efficacy in treatment regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Executive summary of the GESIDA/National AIDS Plan Consensus Document on antiretroviral therapy in adults infected by the human immunodeficiency virus (updated January 2015). Berenguer, J., Polo, R., Aldeguer, JL., et al.[2017]

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 ... The primary efficacy endpoint was the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 (non-inferiority margin 4%). In this ...

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 ... This is a 2-part, phase 3 clinical study evaluating the antiretroviral activity and safety/tolerability of islatravir (ISL), doravirine (DOR), and a fixed dose ...

4. 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) was noninferior to bictegravir/emtricitabine/tenofovir alafenamide in suppressing human immunodeficiency virus type 1 (

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

Brief Report: Efficacy and Safety of Oral Islatravir Once ... Treatment regimens containing islatravir and doravirine maintained viral suppression through week 96 and were well tolerated regardless of dose.