DOR/ISL for HIV

Recruiting at 134 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

500 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a randomized, active-controlled, double-blind clinical study designed to evaluate the antiretroviral activity, safety, and tolerability of doravirine/islatravir (DOR/ISL \[MK-8591A\]) in treatment-naïve participants with human immunodeficiency virus type 1 (HIV-1) infection. It is hypothesized that DOR/ISL is non-inferior to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) \<50 copies/mL at Week 48.

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.

What data supports the effectiveness of the drug DOR/ISL for HIV?

Research shows that the combination of bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) is effective in treating HIV, with studies indicating it works well for both new patients and those switching from other treatments. This combination is known for its strong antiviral effects and low side effects, making it a preferred choice for many patients. ^{1 2 3 4 5}

Is the BIC/FTC/TAF regimen safe for humans?

The BIC/FTC/TAF regimen has been found to be safe and well-tolerated in people living with HIV, including those older than 55 years, with no significant changes in liver or kidney function and no major adverse events reported. ^{4 6 7 8 9}

How is the DOR/ISL drug for HIV different from other HIV drugs?

The DOR/ISL drug for HIV includes components like bictegravir (BIC), which is known for its high resistance to mutations and low drug interactions, making it a strong option for long-term treatment. This combination is unique because it offers a single-tablet regimen that simplifies treatment and improves adherence compared to multi-pill regimens. ^{1 4 6 7 10}

Research Team

Medical Director

Principal Investigator

Merck Sharp & Dohme LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Bictegravir in a fixed-dose tablet with emtricitabine and tenofovir alafenamide for the treatment of HIV infection: pharmacology and clinical implications. [2021]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Outcomes After Switching to BIC/FTC/TAF in Patients with Virological Failure to Protease Inhibitors or Non-Nucleoside Reverse Transcriptase Inhibitors: A Real-World Cohort Study. [2022]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide in HIV late presenters. [2023]

4. Italy pubmed.ncbi.nlm.nih.gov

Clinical pharmacology of the single tablet regimen bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Meta-Analysis of Efficacy and Safety of Coformulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide Among People Living with HIV. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Clinical efficacy, safety, and subjective experience based on ePRO in HIV-infected individuals administered Bictegravir/Emtricitabine/Tenofovir Alafenamide in southwest China. [2023]

7. Switzerland 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. [2023]

8. England pubmed.ncbi.nlm.nih.gov

A possible case of bictegravir-associated severe unconjugated hyperbilirubinemia. [2023]

9. Switzerland 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. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Biktarvy for the treatment of HIV infection: Progress and prospects. [2023]