DOR/ISL Switch for HIV

Not currently recruiting at 50 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Merck Sharp & Dohme LLC

Must be taking: BIC/FTC/TAF

Must not be taking: Immunosuppressants, CYP3A inducers

Disqualifiers: HIV-2, Active AIDS, HBV, HCV, 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 DOR/ISL to determine if it performs as well as or better than the current option, BIC/FTC/TAF. Researchers aim to assess whether DOR/ISL can maintain viral control (HIV-1 RNA <50 copies/mL) and ensure safety and ease of use over 48 weeks. Individuals who have used BIC/FTC/TAF with stable viral suppression for at least three months and have no history of treatment failure may be suitable candidates for this study. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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

Yes, you will need to stop your current HIV medication (BIC/FTC/TAF) to switch to the new study medication (DOR/ISL) as part of the trial.

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

Research shows that the combination of Doravirine and Islatravir (DOR/ISL) is generally well-tolerated. Studies have found that patients taking DOR/ISL experience only minor changes in weight and body composition. There are also no major effects on fasting lipids, which are fats in the blood measured after fasting. About 10% of people reported side effects related to the drug, similar to other HIV treatments like Biktarvy.

Doravirine and Islatravir have been compared to another treatment, Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF), and they share a similar safety profile. People taking DOR/ISL experienced side effects at about the same rate as those on the more established BIC/FTC/TAF treatment.

In summary, the safety data for DOR/ISL is encouraging, showing it is as well-tolerated as existing HIV treatments, with no major safety concerns identified in studies so far. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about DOR/ISL for HIV because it offers a novel combination of medications that could simplify treatment regimens. Unlike standard treatments like BIC/FTC/TAF, which are effective but can be complex, DOR/ISL combines two active ingredients—doravirine and islatravir—into a once-daily pill. This combination not only targets HIV differently but also has the potential to improve adherence by reducing the pill burden. Additionally, DOR/ISL might be more accessible if it becomes commercially available, offering more options for those living with HIV.

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

This trial will compare the effectiveness of Doravirine and Islatravir (DOR/ISL) with the standard treatment of Bictegravir, Emtricitabine, and Tenofovir Alafenamide (BIC/FTC/TAF) for treating HIV. Research has shown that DOR/ISL effectively controls the virus. Studies have found DOR/ISL to be as effective as BIC/FTC/TAF. For instance, one study demonstrated that DOR/ISL was as good as BIC/FTC/TAF at maintaining low HIV virus counts in the blood. Another study found that 85.7% of patients taking DOR/ISL experienced a significant drop in their HIV levels within just a week. These findings suggest that DOR/ISL could be a strong option for managing HIV. ^{1 2 3 4 5}

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 virologically suppressed on BIC/FTC/TAF therapy. Participants must have maintained viral suppression for at least 3 months and cannot be pregnant, breastfeeding, or planning to become pregnant. They should not have a history of treatment failure or resistance to DOR, active hepatitis B or C infections, certain cancers within the last 5 years, or be using strong immune system affecting drugs.

Inclusion Criteria

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

I am not able to have children, or if I can, I am not pregnant or breastfeeding and agree to use birth control or abstain from sex during the study.

I have been on BIC/FTC/TAF for HIV with successful control for over 3 months.

Exclusion Criteria

I am on or might need drugs that strongly affect my immune system.

I have an active hepatitis B infection.

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

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 once daily from day 1 to week 144

144 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

96 weeks

Open-label extension (optional)

Eligible participants may continue on DOR/ISL until week 240 or until DOR/ISL becomes commercially accessible

Up to 96 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BIC/FTC/TAF
• DOR/ISL

Trial Overview The study compares switching HIV-1 positive patients from their current medication (BIC/FTC/TAF) to a new combination drug (DOR/ISL) versus continuing their current regimen. The goal is to see if DOR/ISL maintains virus suppression as effectively as BIC/FTC/TAF after 48 weeks without causing significant side effects.

How Is the Trial Designed?

Group I: DOR/ISL and Placebo to BIC/FTC/TAF Experimental Treatment 2 Interventions

Participants will receive DOR/ISL 100 mg/0.25 mg and Placebo to BIC/FTC/TAF once daily (QD) orally from day 1 to week 144. After week 144, eligible participants may continue on DOR/ISL and continue study treatment until week 240 or to when DOR/ISL becomes commercially accessible (whichever comes first).

Group II: BIC/FTC/TAF and Placebo to DOR/ISL Active Control 2 Interventions

Participants will receive BIC/FTC/TAF 50 mg/200 mg/25 mg and Placebo to DOR/ISL once daily (QD) orally from day 1 to week 144. After week 144, eligible participants may switch to DOR/ISL and continue study treatment until week 240 or to when DOR/ISL becomes commercially accessible (whichever comes first).

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

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. 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 (

4. 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 ...

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 ...