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NCT Number: NCT05630755

A Switch to Doravirine/Islatravir (DOR/ISL) in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) (MK-8591A-052)

The primary objectives of this study are to evaluate the antiretroviral activity of a switch to Doravirine/Islatravir (DOR/ISL) compared with continued Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) at Week 48; and to evaluate the safety and tolerability of a switch to DOR/ISL compared with continued BIC/FTC/TAF, through Week 48. The primary hypotheses are that (1) DOR/ISL is non-inferior to continued BIC/FTC/TAF, 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; and (2) DOR/ISL is superior to BIC/FTC/TAF, as assessed by the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48.

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 6200), 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.

The key inclusion and exclusion criteria include but are not limited to the following:

Inclusion criteria

  • Is HIV-1 positive with plasma HIV-1 RNA <50 copies/mL
  • Has been receiving BIC/FTC/TAF therapy 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 participant of childbearing potential, not pregnant or breastfeeding, and is willing to use an acceptable contraceptive method or abstain from heterosexual intercourse for study duration

Exclusion criteria

  • Has HIV-2 infection
  • 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 with laboratory values consistent with cirrhosis
  • Has a history of malignancy ≤5 years prior to providing documented 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 strong and moderate cytochrome P450 3A (CYP3A) inducers
  • Has a documented or known virologic resistance to DOR
  • Has taken long-acting HIV therapy at any time (e.g., cabotegravir, lenacapavir)
  • 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 except those currently enrolled in the comparator arm of an ongoing DOR/ISL study

Treatment and study plan

DOR/ISL

Drug

DOR/ISL 100 mg/0.25 mg oral tablets once daily

Other names: MK-8591A, Doravirine/Islatravir

BIC/FTC/TAF

Drug

BIC/FTC/TAF 50 mg/200 mg/25 mg oral tablets once daily

Other names: Bictegravir/Emtricitabine/Tenofovir Alafenamide

Placebo to BIC/FTC/TAF

Drug

0 mg oral tablets once daily

Placebo to DOR/ISL

Drug

0 mg oral tablets once daily

Primary outcomes

  1. Percentage of Participants With Human Immunodeficiency Virus Type 1 (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 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 Who Experience Adverse Events (AEs) Through Week 48

    Time frame: Up to Week 48

    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 is reported.

  3. Percentage of Participants Who Discontinue Study Intervention Due to AEs Through Week 48

    Time frame: Up to Week 48

    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 is 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 blood samples taken at each visit were measured 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 blood samples taken at each visit were measured 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. Change From Baseline in Cluster of Differentiation 4-positive (CD4+) T-cell Count at 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 change from baseline to Week 48 and corresponding 2-sided 95% confidence intervals were calculated based on cLDA models adjusted by treatment group, time, and the interaction of time-by-treatment group.

  4. 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. Per protocol, 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.

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

    Time frame: Week 96

    Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 96 will be reported.

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

    Time frame: Week 96

    Percentage of participants with HIV-1 RNA <200 copies/mL at Week 96 will be reported.

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

    Time frame: Week 96

    Percentage of participants with HIV-1 RNA <50 copies/mL at Week 96 will be reported.

  8. Change From Baseline in CD4+ T-cell Count at 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 will be reported.

  9. Number of Participants With Viral Drug Resistance Mutations at Week 96

    Time frame: Week 96

    Number of participants with evidence of viral drug resistance-associated substitutions at Week 96 will be reported.

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

    Time frame: Week 144

    Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 144 will be reported.

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

    Time frame: Week 144

    Percentage of participants with HIV-1 RNA <200 copies/mL at Week 144 will be reported.

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

    Time frame: Week 144

    Percentage of participants with HIV-1 RNA <50 copies/mL at Week 144 will be reported.

  13. Change From Baseline in CD4+ T-cell Count at 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 will be reported.

  14. Number of Participants With Viral Drug Resistance Mutations at Week 144

    Time frame: Week 144

    Number of participants with evidence of viral drug resistance-associated substitutions at Week 144 will be reported.

  15. Percentage of Participants Who Experience AEs Through Week 144

    Time frame: Up to Week 144

    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 intervention.

  16. Percentage of Participants Who Discontinue Study Intervention Due to AEs Through Week 144

    Time frame: Up to Week 144

    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 intervention.

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 a Switch to Doravirine/Islatravir (DOR/ISL 100 mg/0.25 mg) Once-Daily in Participants With HIV-1 Who Are Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF)

Important dates

Study start
2023
Primary completion
2024
Study completion
2028
First posted
Nov 30, 2022
Registry last updated
Nov 18, 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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