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Randomized, Double-blind, Efficacy, and Safety Study of Doravirine/Islatravir (DOR/ISL) in Treatment-naïve Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Infection (MK-8591A-020)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04233879
Recruitment Status : Recruiting
First Posted : January 18, 2020
Last Update Posted : August 7, 2020
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

Brief Summary:
This is a phase 3, randomized, controlled, double-blind clinical study of a once-daily fixed dose combination (FDC) of 100 mg doravirine/0.75 mg islatravir (DOR/ISL [also known as MK-8591A]) in treatment-naïve participants with human immunodeficiency virus type-1 (HIV-1) infection. The primary hypothesis is that DOR/ISL is non-inferior to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) treatment based on the percentage of participants with HIV-1 ribonucleic acid (RNA) <50 copies/mL at Week 48.

Condition or disease Intervention/treatment Phase
HIV-1 Infection Drug: DOR/ISL Drug: BIC/FTC/TAF Drug: Placebo to BIC/FTC/TAF Drug: Placebo to DOR/ISL Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 680 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Phase 3 Randomized, Active-Controlled, Double-Blind Clinical Study to Evaluate the Antiretroviral Activity, Safety, and Tolerability of Doravirine/Islatravir Once-Daily in HIV-1 Infected Treatment-Naïve Participants
Actual Study Start Date : February 28, 2020
Estimated Primary Completion Date : December 20, 2023
Estimated Study Completion Date : December 20, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Group 1: DOR/ISL
Treatment-naïve participants with HIV-1 receive DOR/ISL and placebo to BIC/FTC/TAF once daily (QD) for 96 weeks.
Drug: DOR/ISL
100 mg DOR/0.75 mg ISL FDC tablet taken once daily by mouth.
Other Names:
  • MK-8591A
  • Doravirine/islatravir

Drug: Placebo to BIC/FTC/TAF
Placebo tablet matched to BIC/FTC/TAF taken by mouth.

Active Comparator: Group 2: BIC/FTC/TAF
Treatment-naïve participants with HIV-1 receive BIC/FTC/TAF and placebo to DOR/ISL QD for 96 weeks.
Drug: BIC/FTC/TAF
BIC/FTC/TAF 50/200/25 mg FDC tablet taken once daily by mouth.
Other Name: Bictegravir/emtricitabine/tenofovir alafenamide

Drug: Placebo to DOR/ISL
Placebo tablet matched to DOR/ISL taken by mouth.




Primary Outcome Measures :
  1. Percentage of participants with HIV-1 RNA <50 copies/mL [ Time Frame: Week 48 ]
    The percentage of participants with HIV-1 RNA <50 copies/mL will be determined at the central laboratory with an Abbott Real Time Polymerase Chain Reaction (PCR) assay with a lower limit of detection (LLOD) of 40 copies/mL.

  2. Percentage of participants experiencing ≥1 adverse events (AEs) [ Time Frame: Up to 98 weeks ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study interventions.

  3. Percentage of participants discontinuing from study treatment due to AE(s) [ Time Frame: Up to 96 weeks ]
    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study interventions.


Secondary Outcome Measures :
  1. Percentage of participants with HIV-1 RNA <50 copies/mL [ Time Frame: Week 96 ]
    The percentage of participants with HIV-1 RNA <50 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL.

  2. Percentage of participants with HIV-1 RNA <40 copies/mL [ Time Frame: Week 48 ]
    The percentage of participants with HIV-1 RNA <40 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL.

  3. Percentage of participants with HIV-1 RNA <200 copies/mL [ Time Frame: Week 48 ]
    The percentage of participants with HIV-1 RNA <200 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL.

  4. Percentage of participants with HIV-1 RNA <40 copies/mL [ Time Frame: Week 96 ]
    The percentage of participants with HIV-1 RNA <40 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL.

  5. Percentage of participants with HIV-1 RNA <200 copies/mL [ Time Frame: Week 96 ]
    The percentage of participants with HIV-1 RNA <200 copies/mL will be determined. The central laboratory will measure plasma HIV-1 RNA using an Abbott Real Time PCR assay with a LLOD of 40 copies/mL.

  6. Change from baseline in cluster of differentiation 4+ (CD4+) T-cell counts [ Time Frame: Day 1 (baseline) and Week 48 ]
    CD4+ T-cell counts will be measured by a central laboratory.

  7. Change from baseline in cluster of differentiation 4+ (CD4+) T-cell counts [ Time Frame: Day 1 (baseline) and Week 96 ]
    CD4+ T-cell counts will be measured by a central laboratory.

  8. Incidence of viral resistance-associated substitutions (RASs) [ Time Frame: Week 48 ]
    The incidence of viral RASs will be determined.

  9. Incidence of viral RASs [ Time Frame: Week 96 ]
    The incidence of viral RASs will be determined.

  10. Change from baseline in body weight [ Time Frame: Day 1 (baseline) and Week 48 ]
    The change from baseline in participant body weight will be determined.

  11. Change from baseline in body weight [ Time Frame: Day 1 (baseline) and Week 96 ]
    The change from baseline in participant body weight will be determined.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Is HIV-1 positive
  • Is naïve to antiretroviral therapy (ART) defined as having received ≤10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection including prevention of mother-to-child transmission up to 1 month prior to screening.
  • A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: 1) Is not a woman of childbearing potential (WOCBP); 2) Is a WOCBP and using an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis); 3) A WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 24 hours before the first dose of study intervention; 4) If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required

Exclusion Criteria:

  • Has HIV-2 infection
  • Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
  • Has an active diagnosis of hepatitis due to any cause, including active HBV infection (defined as hepatitis B surface antigen [HBsAg]-positive or hepatitis B virus deoxyribonucleic acid [HBV DNA]-positive)
  • Has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or cutaneous Kaposi's sarcoma
  • 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
  • Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1
  • Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapy from 45 days prior to Day 1 through the study intervention period
  • 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 intervention period
  • Has a documented or known virologic resistance to any approved HIV-1 reverse transcriptase inhibitor, or any study intervention
  • Has exclusionary laboratory values within 45 days prior to Day 1
  • Is female and is expecting to conceive or donate eggs at any time during the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04233879


Contacts
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Contact: Toll Free Number 1-888-577-8839 Trialsites@merck.com

Locations
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Sponsors and Collaborators
Merck Sharp & Dohme Corp.
Investigators
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Study Director: Medical Director Merck Sharp & Dohme Corp.
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Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT04233879    
Other Study ID Numbers: 8591A-020
MK-8591A-020 ( Other Identifier: Merck Protocol Number )
2019-000590-23 ( EudraCT Number )
First Posted: January 18, 2020    Key Record Dates
Last Update Posted: August 7, 2020
Last Verified: August 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Infection
Tenofovir
Emtricitabine
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents