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NCT Number: NCT05631093

A Switch to Doravirine/Islatravir (DOR/ISL) in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are Virologically Suppressed on Antiretroviral Therapy (ART) (MK-8591A-051)

The primary objectives of this study are to evaluate the safety and tolerability of a switch to Doravirine/Islatravir (DOR/ISL) compared with continued baseline antiretroviral therapy (ART), through Week 48; and to evaluate the antiretroviral activity of a switch to DOR/ISL compared with continued baseline ART at Week 48. The primary hypothesis is that DOR/ISL is non-inferior to continued baseline ART, as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48, with a margin of 4 percentage points used to define non-inferiority.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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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

Holdsworth House Medical Practice ( Site 4200), Darlinghurst, New South Wales, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Is Human Immunodeficiency Virus-1 (HIV-1) positive with plasma HIV-1 Ribonucleic Acid (RNA) <50 copies/mL at screening
  • Has been receiving continuous, stable oral 2-drug or 3-drug combination (± PK booster) antiretroviral therapy ART with documented viral suppression (HIV-1 RNA <50 copies/mL) for ≥3 consecutive months prior to providing documented informed consent and has no history of prior virologic treatment failure on any past or current regimen
  • Female is not a participant of childbearing potential (POCBP); or if a POCBP uses an acceptable contraceptive method or abstains from penile-vaginal intercourse as their preferred and usual lifestyle; has a negative highly sensitive pregnancy test; and whose medical history, menstrual history, and recent sexual activity has been reviewed by the investigator

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 a diagnosis of an active acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 30 days prior to screening
  • Has active hepatitis B virus (HBV) infection
  • Has chronic hepatitis C virus (HCV) infection consistent with cirrhosis
  • Has a ≤5 years prior history of malignancy
  • Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or strong and moderate cytochrome P450 3A (CYP3A) inducers
  • Has taken long-acting HIV therapy at any time
  • Is currently participating in or has participated in a clinical study and received (or is receiving) 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 Doravine (DOR)

Treatment and study plan

ART

Drug

Standard of care ART, per approved product list, taken orally

DOR/ISL

Drug

Single tablet combination of 100 mg doravirine (DOR) with 0.25 mg Islatravir (ISL) in tablet form, taken orally, once daily.

Other names: MK-8591A

Primary outcomes

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

    Time frame: Week 48

    HIV-1 RNA levels in plasma were measured by polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 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) at Week 48

    Time frame: Up to Week 48

    An AE is 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 Day 1 up to Week 48 are reported.

  3. Percentage of Participants With an AE Leading to Discontinuation of Study Intervention at Week 48

    Time frame: Up to Week 48

    An AE is 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 leading to discontinuation of study intervention from Day 1 up to Week 48 are reported.

Secondary outcomes

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

    Time frame: Week 48

    HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA <200 copies/mL at Week 48 is presented using the FDA Snapshot missing data approach.

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

    Time frame: Week 48

    HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 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.

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

    Time frame: Week 96

    HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA <200 copies/mL at Week 96 is presented using the FDA Snapshot missing data approach.

  4. Participants With HIV-1 RNA <200 Copies/mL at Week 144

    Time frame: Week 144

    HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA <200 copies/mL at Week 144 is presented using the FDA Snapshot missing data approach.

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

    Time frame: Week 96

    HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 96 is presented using the FDA Snapshot missing data approach.

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

    Time frame: Week 144

    HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 144 is presented using the FDA Snapshot missing data approach.

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

    Time frame: Week 96

    HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 96 is presented using the FDA Snapshot missing data approach.

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

    Time frame: Week 144

    HIV-1 RNA levels in plasma were measured by a polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of <50 copies/mL. The percentage of participants with HIV-1 RNA <50 copies/mL at Week 144 is presented using the FDA Snapshot missing data approach.

  9. Mean Change of Plasma Cluster of Differentiation 4 (CD4+) T-Cell Count From Baseline Day 1 to Week 48

    Time frame: Baseline at Day 1 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 mean change of plasma CD4+ T-Cell count from baseline to Week 48 is presented.

  10. Mean Change of Plasma CD4+ T-Cell Count From Baseline Week 48 to Week 96

    Time frame: Baseline at Week 48 and Week 96

    Mean change from baseline at Week 48 in CD4+ T-cell count at Week 96. This outcome measure is applicable to participants who were randomized to switch to DOR/ISL at Week 48.

  11. Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 48 to Week 144

    Time frame: Baseline at Week 48 and Week 144

    Mean change from baseline at Week 48 in CD4+ T-cell count at Week 144. This outcome measure is applicable to participants who were randomized to switch to DOR/ISL at Week 48.

  12. Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 1 to Week 96

    Time frame: Baseline at Day 1 and Week 96

    Mean change from baseline at Day 1 in CD4+ T-cell count at Week 96. This outcome measure is applicable to those randomized to start DOR/ISL on Day 1.

  13. Mean Change of Plasma CD4+ T-Cell Count From Baseline Day 1 to Week 144

    Time frame: Baseline at Day 1 and Week 144

    Mean change from baseline at Day 1 in CD4+ T-cell count at Week 144. This outcome measure is applicable to those randomized to start DOR/ISL on Day 1.

  14. Percentage of Participants With Treatment-Emergent, Resistance-associated Substitutions at Week 48

    Time frame: Up to Week 48

    Participants with clinically significant confirmed viremia [2 consecutive occurences 4 weeks (+-1 week) apart of HIV-1 RNA >=200 copies/mL at any time during the study] or who discontinue study intervention for another reason with HIV-1 RNA >=200 copies/mL at the time of discontinuation met the criteria for post-baseline resistance testing. Participants with HIV-1 RNA >=400 copies/mL or any participant for whom available genotypic or phenotypic data show evidence of resistance, irrespective of viral load were included in the resistance analysis subset. Plasma samples were collected for genotypic and phenotypic HIV-1 viral drug resistance testing and used to assess resistance-associated substitutions and virus susceptibility to study intervention. The percentage of participants in the resistance analysis subset with treatment-emergent resistance-associated substitutions to the study intervention is presented.

  15. Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48

    Time frame: Baseline and Week 48

    Blood serum samples were taken at baseline and Week 48. The mean change from baseline in fasting Low density lipoprotein cholesterol (LDL-C) at Week 48 is presented for PI-containing regimens (including PI- + InSTI-containing regimens), non-PI- and non-InSTI-containing regimens, and InSTI-containing regimens (non-PI-containing regimens) are presented.

  16. Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48

    Time frame: Baseline and Week 48

    Blood serum samples were taken at baseline and Week 48. The mean change from baseline in fasting Non-HDL-C at Week 48 is presented for PI-containing regimens (including PI- + InSTI-containing regimens), non-PI- and non-InSTI-containing regimens, and InSTI-containing regimens (non-PI-containing regimens) are presented.

  17. Participants With One or More AEs at Week 96

    Time frame: Up to Week 96

    An AE is 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 Day 1 up to Week 96 is reported.

  18. Participants With One or More AEs at Week 144

    Time frame: Up to Week 144

    An AE is 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 Day 1 up to Week 144 is reported.

  19. Percentage of Participants With AEs Leading to Discontinuation of Study Intervention at Week 96

    Time frame: Up to Week 96

    An AE is 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 leading to discontinuation of study intervention from Day 1 up to Week 96 are reported.

  20. Percentage of Participants With AEs Leading to Discontinuation of Study Intervention at Week 144

    Time frame: Up to Week 144

    An AE is 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 leading to discontinuation of study intervention from Day 1 up to Week 144 are reported.

  21. Percentage of Participants With One or More AEs From Week 48 up to Week 96

    Time frame: Week 48 up to Week 96

    An AE is 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.

  22. Percentage of Participants With One or More AEs From Week 48 up to Week 144

    Time frame: Week 48 up to Week 144

    An AE is 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 144 is presented.

  23. Percentage of Participants With AEs Leading to Discontinuation of Study Intervention From Week 48 up to Week 96

    Time frame: Week 48 up to Week 96

    An AE is 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 leading to discontinuation of study intervention from Week 48 up to Week 96 are reported.

  24. Percentage of Participants With AEs Leading to Discontinuation of Study Intervention From Week 48 up to Week 144

    Time frame: Week 48 up to Week 144

    An AE is 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 leading to discontinuation of study intervention from Week 48 up to Week 144 are reported.

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 100 mg/0.25 mg) Once-Daily in Participants With HIV-1 Who Are Virologically Suppressed on Antiretroviral Therapy

Important dates

Study start
2023
Primary completion
2024
Study completion
2028
First posted
Nov 30, 2022
Registry last updated
Nov 21, 2025

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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