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Completed

NCT Number: NCT04223778

Safety and Efficacy of a Switch to Doravirine/Islatravir in Participants With HIV-1 (MK-8591A-017)

This study will evaluate the safety and efficacy of a switch to MK-8591A (a fixed dose combination of doravirine and islatravir) in human immunodeficiency virus -1 (HIV-1)-infected participants virologically suppressed on a protocol-specified antiretroviral regimen. The primary hypothesis is that a switch to MK-8591A will be non-inferior to continued treatment with baseline antiretroviral therapy (ART) as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48.

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Key information

Conditions

HIV Infection Blood-Borne Infections Communicable Diseases Genital Diseases HIV Infections Immune System Diseases Immunologic Deficiency Syndromes Infections Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Urogenital Diseases Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Holdsworth House Medical Practice ( Site 2300), Sydney, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Is human immunodeficiency virus (HIV-1) positive
  • Has been receiving continuous, stable oral 2-drug or 3-drug combination (± pharmacokinetic (PK) booster) with documented viral suppression (HIV-1 RNA <50 copies/mL) for ≥3 months prior to signing informed consent and has no history of prior virologic treatment failure on any past or current regimen.
  • Females are eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: is not a woman of childbearing potential (WOCBP); is a WOCBP and using an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle; 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; if a urine test cannot be confirmed as negative (e.g. an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive

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 Hepatitis B Virus (HBV) co-infection
  • 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
  • Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies
  • Is currently taking long-acting cabotegravir-rilpivirine
  • 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 treatment period
  • Has a documented or known virologic resistance to doravirine (DOR)
  • Expects to conceive or donate eggs at any time during the study

Treatment and study plan

DOR/ISL

Drug

A FDC of 100 mg DOR/ 0.75 mg ISL taken in tablet form, orally, once daily

Other names: MK-8591A

ART

Drug

Baseline ART regimen will be administered as per approved label. ART medication will not be provided by the Sponsor; participants will provide their own ART medications. Allowed drug classes include nucleoside analog reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase strand transferase inhibitors (InSTIs), fusion inhibitors, chemokine receptor 5 (CCR5) antagonists, post-attachment inhibitor, and pharmacokinetic (PK) boosters.

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

    HIV-1 RNA levels in blood samples taken at each visit were measured by the Abbott RealTime polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.

  2. Percentage of Participants With One or More Adverse Events (AEs) up to Week 48

    Time frame: Up to ~48 Weeks

    An AE was defined as 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 intervention. The percentage of participants who experienced at least one AE was reported.

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

    Time frame: Up to ~48 Weeks

    An AE was defined as 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 intervention. The percentage of participants who discontinued study intervention due to an AE was reported.

Secondary outcomes

  1. Percentage of Participants With HIV-1 RNA <40 or <50 Copies/mL at Week 48

    Time frame: Week 48

    HIV-1 RNA levels in blood samples taken at each visit were measured by the Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA <40 copies/mL or <50 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.

  2. Group 2 (Switch-Over): Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96

    Time frame: Week 96

    HIV-1 RNA levels in blood samples taken at each visit was measured by the Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL, or <50 copies/mL at Week 96 is reported for Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96. Per protocol, the percentage of participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL, or <50 copies/mL at Week 96 for Group 1 participants is a separate outcome measure and is presented later in the record.

  3. Group 1: Percentage of Participants With HIV-1 RNA ≥50 Copies/mL, <40 Copies/mL or <50 Copies/mL at Week 96

    Time frame: Week 96

    HIV-1 RNA levels in blood samples taken at each visit was measured by the Abbott RealTime PCR assay with a reliable lower limit of quantification of 40 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL, or <50 copies/mL at Week 96 is reported for Group 1 participants. Per protocol, the percentage of participants with HIV-1 RNA ≥50 copies/mL, <40 copies/mL, or <50 copies/mL at Week 96 for Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96 is a separate outcome measure and is presented earlier in the record.

  4. Percentage Change From Baseline in CD4+ T-cell Count at Week 48

    Time frame: Baseline and Week 48

    Plasma CD4+ T-Cell Count was measured in cells/mm^3 for baseline and 48 weeks. Baseline measurements were defined as the Day 1 value of each participant. The percentage change from baseline to Week 48 is presented.

  5. Group 1: Percentage Change From Baseline in CD4+ T-cell Count at Week 96

    Time frame: Baseline and Week 96

    Plasma CD4+ T-Cell Count was measured in cells/mm^3 for baseline and 96 weeks. Baseline measurements were defined as the Day 1 value of each participant. The mean percent change from baseline to Week 96 in CD4+ T-cell count is reported for Group 1 participants. Per protocol, the mean percentage change from baseline in CD4+ T-cell count at Week 96 for Group 2 participants was not planned or conducted.

  6. Group 1 & Group 2 (Switch-Over): Percentage Change From Week 48 in CD4+ T-cell Count at Week 96

    Time frame: Week 48 and Week 96

    Plasma CD4+ T-Cell Count was measured in cells/mm^3 for Week 48 and Week 96. The mean percent change from Week 48 to Week 96 is reported for Group 1 and Group 2 participants who delayed switch over from baseline ART to DOR/ISL Week 48 to Week 96.

  7. Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 48

    Time frame: Week 48

    Viral drug resistance is defined as participants with confirmed HIV-1 RNA ≥400 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The percentage of participants who demonstrated drug resistance at Week 48 is presented.

  8. Percentage of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 96

    Time frame: Week 96

    Viral drug resistance was defined as participants with confirmed HIV-1 RNA ≥400 copies/mL and/or genotypic or phenotypic analysis of data showing evidence of resistance to the study drug administered. The percentage of participants who demonstrate drug resistance at Week 96 is presented for Group 1 and Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96. Per protocol, the percentage of participants with evidence of viral drug resistance-associated substitutions from week 0 to week 48 for Group 1 and Group 2 participants is a separate outcome measure and is presented earlier in the record.

  9. Change From Baseline to Week 24 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens)

    Time frame: Baseline and Week 24

    Blood serum samples were taken at baseline and Week 24. Per protocol, this outcome analysis was conducted in participants on PI-containing regimens (including PI- and InSTI-containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 24 in fasting lipids is presented.

  10. Change From Baseline to Week 24 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens)

    Time frame: Baseline and Week 24

    Blood serum samples were taken at baseline and Week 24. Per protocol, this outcome analysis was conducted in participants on InSTI-based regimens (non-PI containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 24 in fasting lipids is presented.

  11. Change From Baseline to Week 24 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens

    Time frame: Baseline and Week 24

    Blood serum samples were taken at baseline and Week 24. Per protocol, this outcome analysis was conducted in participants on all other non-PI- and non-InSTI containing regimens, excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 24 in fasting lipids is presented.

  12. Change From Baseline to Week 48 in Fasting Lipids in Participants on Protease Inhibitor (PI)-Containing Regimens (Including PI- and Integrase Strand Transferase Inhibitor [InSTI]-Containing Regimens)

    Time frame: Baseline and Week 48

    Blood serum samples were taken at baseline and Week 48. Per protocol, this outcome analysis was conducted in participants on PI-containing regimens (including PI- and InSTI-containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 48 in fasting lipids is presented.

  13. Change From Baseline to Week 48 in Fasting Lipids in Participants on InSTI-based Regimens (Non-PI Containing Regimens)

    Time frame: Baseline and Week 48

    Blood serum samples were taken at baseline and Week 48. Per protocol, this outcome analysis was conducted in participants on InSTI-based regimens (non-PI containing regimens), excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 48 in fasting lipids is presented.

  14. Change From Baseline to Week 48 in Fasting Lipids in Participants on All Other Non-PI- and Non-InSTI Containing Regimens

    Time frame: Baseline and Week 48

    Blood serum samples were taken at baseline and Week 48. Per protocol, this outcome analysis was conducted in participants on all other non-PI- and non-InSTI containing regimens, excluding participants who took lipid-lowering therapy during the study. The fasting lipids consisted of fasting cholesterol, fasting HDL cholesterol, fasting LDL cholesterol, fasting non-HDL cholesterol, and fasting triglycerides. The mean change from baseline to Week 48 in fasting lipids is presented.

  15. Change From Baseline in Body Weight at Week 48 for InSTI-based Regimens (Non-PI-containing Regimens)

    Time frame: Baseline and Week 48

    Baseline measurements were defined as the Day 1 value of each participant. The change from baseline in body weight to Week 48 is presented for participants who received InSTI- based regimens.

  16. Group 1: Percentage of Participants With One or More AEs up to Week 96

    Time frame: Up to ~96 Weeks

    An AE was defined as 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 intervention. The percentage of participants who experienced at least one AE up to Week 96 is reported for Group 1 participants. Per protocol, the percentage of participants with one or more AEs for Group 2 participants is a separate outcome measure and is presented later in the record.

  17. Group 1: Percentage of Participants Who Discontinued Study Intervention Due to an AE up to Week 96

    Time frame: Up to ~96 Weeks

    An AE was defined as 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 intervention. The percentage of participants who discontinued study intervention due to an AE up to Week 96 is reported for Group 1 participants. Per protocol, the percentage of participants who discontinued study intervention for Group 2 participants is a separate outcome measure and is presented later in the record.

  18. Group 1 & Group 2 (Switch-Over): Percentage of Participants With One or More AEs From Week 48 to Week 96

    Time frame: Weeks 48-96 (up to ~48 weeks)

    An AE was defined as 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 intervention. The percentage of participants who experienced at least one AE from Week 48 up to Week 96 is reported for Group 1 participants and Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96.

  19. Group 1 & Group 2 (Switch-Over): Percentage of Participants Who Discontinued Study Intervention Due to an AE From Week 48 to Week 96

    Time frame: Weeks 48-96 (up to ~48 weeks)

    An AE was defined as 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 intervention. The percentage of participants who discontinued study intervention due to an AE from Week 48 up to Week 96 is reported for Group 1 participants and Group 2 participants who delayed switch over from baseline ART to DOR/ISL from Week 48 to Week 96.

Sponsors and collaborators

Lead sponsor

Merck Sharp & Dohme LLC

Industry

Registry information

Official study title

A Phase 3 Randomized, Active-Controlled, Open-Label Clinical Study to Evaluate a Switch to Doravirine/Islatravir (DOR/ISL) Once-Daily in Participants With HIV-1 Virologically Suppressed on Antiretroviral Therapy

Important dates

Study start
2020
Primary completion
2021
Study completion
2024
First posted
Jan 10, 2020
Registry last updated
Feb 18, 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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