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OpenTrials
Completed

NCT Number: NCT04233879

Study of Doravirine/Islatravir (DOR/ISL 100 mg/0.75 mg) to Evaluate the Antiretroviral Activity, Safety, and Tolerability in Treatment-Naïve Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Infection (MK-8591A-020)

This is a phase 3, randomized, controlled, double-blind, multisite 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 living with human immunodeficiency virus type-1 (HIV-1) infection. The primary objectives are to evaluate the antiretroviral activity, safety, and tolerability of DOR/ISL compared to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). The primary hypothesis is that DOR/ISL is noninferior or superior to BIC/FTC/TAF treatment based on the percentage of participants with HIV-1 ribonucleic acid (RNA) <50 copies/mL at Week 48.

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Key information

Conditions

HIV-1 Infection

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Helios Salud S.A. ( Site 5802), Buenos Aires, Buenos Aires F.D., Argentina

Loading trial locations.

About this study

Double-blind treatment with the assigned intervention occurs from Day 1 to Week 96, followed by an open-label portion up to Week 144. Participants who benefit from treatment in the opinion of the Investigator may continue their assigned intervention up to Week 168 (or until they have the option to enroll in a DOR/ISL 100 mg/0.25 mg study, whichever is sooner).

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Is human immunodeficiency virus type 1 (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 human immunodeficiency virus type 2 (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 hepatitis B virus (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

Treatment and study plan

DOR/ISL

Drug

100 mg DOR/0.75 mg ISL FDC single tablet taken once daily by mouth.

Other names: MK-8591A, Doravirine/islatravir

BIC/FTC/TAF

Drug

BIC/FTC/TAF 50/200/25 mg FDC single tablet taken once daily by mouth.

Other names: Bictegravir/emtricitabine/tenofovir alafenamide

Placebo to BIC/FTC/TAF

Drug

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

Placebo to DOR/ISL

Drug

Placebo single tablet matched to DOR/ISL taken by mouth.

Primary outcomes

  1. Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48

    Time frame: Week 48

    The Abbott RealTime polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 48 was presented using the Food and Drug Administration (FDA) Snapshot missing data approach. The final analysis for this outcome is presented here.

  2. Percentage of Participants Who Experienced an Adverse Event (AE) up to Week 48

    Time frame: Up to approximately 48 weeks

    An AE was any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who experienced at least one AE up to Week 48 was reported. The final analysis for this outcome is presented here.

  3. Percentage of Participants Who Discontinued Study Treatment Due to an AE up to Week 48

    Time frame: Up to approximately 48 weeks

    An AE was any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who discontinued study treatment due to an AE up to Week 48 were reported. The final analysis for this outcome is presented here.

Secondary outcomes

  1. Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96

    Time frame: Week 96

    The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 96 was presented using the FDA Snapshot missing data approach. The final analysis for this outcome is presented here.

  2. Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 144

    Time frame: Week 144

    The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 144 was presented using the Data as Observed (DAO) missing data approach. The final analysis for this outcome is presented here.

  3. Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48

    Time frame: Week 48

    The percentage of participants with HIV-1 RNA <40 copies/mL was determined. The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <40 copies/mL at Week 48 was presented using the FDA Snapshot missing data approach. The final analysis for this outcome is presented here.

  4. Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48

    Time frame: Week 48

    The percentage of participants with HIV-1 RNA <200 copies/mL was determined. The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <200 copies/mL at Week 48 was presented using the FDA Snapshot missing data approach. The final analysis for this outcome is presented here.

  5. Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96

    Time frame: Week 96

    The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <40 copies/mL at Week 96 was presented using the FDA Snapshot missing data approach. The final analysis for this outcome is presented here.

  6. Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96

    Time frame: Week 96

    The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <200 copies/mL at Week 96 was presented using the FDA Snapshot missing data approach. The final analysis for this outcome is presented here.

  7. Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 144

    Time frame: Week 144

    The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <40 copies/mL at Week 144 was presented using the DAO missing data approach. The final analysis for this outcome is presented here.

  8. Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 144

    Time frame: Week 144

    The Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA <200 copies/mL at Week 144 was presented using the DAO missing data approach. The final analysis for this outcome is presented here.

  9. Mean Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 48

    Time frame: Baseline (Day 1) and Week 48

    Plasma CD4+ T-cell count was measured in cells/mm^3 for baseline and at Week 48 by a central laboratory. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in CD4+ T-cell count at Week 48 using the Data as Observed (DAO) approach was presented. The final analysis for this outcome is presented here.

  10. Mean Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 96

    Time frame: Baseline (Day 1) and Week 96

    Plasma CD4+ T-cell count was measured in cells/mm^3 for baseline and at Week 96 by a central laboratory. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in CD4+ T-cell count at Week 96 using the Data as Observed (DAO) approach was presented. The final analysis for this outcome is presented here.

  11. Mean Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 144

    Time frame: Baseline (Day 1) and Week 144

    Plasma CD4+ T-cell count was measured in cells/mm^3 for baseline and at Week 144 by a central laboratory. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in CD4+ T-cell count at Week 144 using the Data as Observed (DAO) approach was presented. The final analysis for this outcome is presented here.

  12. Incidence of Viral Resistance-Associated Substitutions (RASs) at Week 48

    Time frame: Week 48

    RASs was defined as participants with confirmed HIV-1 RNA ≥200 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The number of participants who demonstrated RASs at Week 48 was presented. The final analysis for this outcome is presented here.

  13. Incidence of Viral RASs at Week 96

    Time frame: Week 96

    RASs was defined as participants with confirmed HIV-1 RNA ≥200 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The number of participants who demonstrated RASs at Week 96 was presented. The final analysis for this outcome is presented here.

  14. Incidence of Viral RASs at Week 144

    Time frame: Week 144

    RASs was defined as participants with confirmed HIV-1 RNA ≥200 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The number of participants who demonstrated RASs at Week 144 was presented. The final analysis for this outcome is presented here.

  15. Mean Change From Baseline in Body Weight at Week 48

    Time frame: Baseline (Day 1) and Week 48

    Body weight was measured at baseline and at Week 48. Participants removed their shoes and wore a single layer of clothing at each measurement. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in body weight at Week 48 was presented. The final analysis for this outcome is presented here.

  16. Mean Change From Baseline in Body Weight at Week 96

    Time frame: Baseline (Day 1) and Week 96

    Body weight was measured at baseline and at Week 96. Participants removed their shoes and wore a single layer of clothing at each measurement. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in body weight at Week 96 was presented. The final analysis for this outcome is presented here.

  17. Mean Change From Baseline in Body Weight at Week 144

    Time frame: Baseline (Day 1) and Week 144

    Body weight was measured at baseline and at Week 144. Participants removed their shoes and wore a single layer of clothing at each measurement. Baseline measurements were defined as the Day 1 value of each participant. The mean change from baseline in body weight at Week 144 was presented. The final analysis for this outcome is presented here.

  18. Percentage of Participants Who Experienced an Adverse Event (AE)

    Time frame: Up to approximately 47 months

    An AE was any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who experienced at least one or more AEs is presented. Per protocol, pregnancy-related AEs collected for enrolled participants are reported separately and are presented in the AE module. The final analysis for this outcome is presented here.

  19. Percentage of Participants Who Discontinued Study Treatment Due to an AE

    Time frame: Up to approximately 38 months

    An AE was any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who discontinued study intervention due to an AE is presented. Per protocol, pregnancy-related AEs collected for enrolled participants are reported separately and are presented in the AE module. The final analysis for this outcome is presented here.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study 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

Important dates

Study start
2020
Primary completion
2022
Study completion
2025
First posted
Jan 18, 2020
Registry last updated
Jun 3, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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