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Completed

NCT Number: NCT04223791

Switch to Doravirine/Islatravir (DOR/ISL) in Human Immunodeficiency Virus 1 (HIV-1) Participants Treated With Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) (MK-8591A-018)

This study will evaluate the safety and efficacy of a switch to Doravirine/Islatravir (DOR/ISL) (MK-8591A) (a fixed dose combination of doravirine 100 mg and islatravir 0.75 mg) in participants living with human immunodeficiency virus-1 (HIV-1) virologically suppressed on a regimen of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). The primary hypothesis is that a switch to DOR/ISL (MK-8591A) will be non-inferior to continued treatment with BIC/FTC/TAF as assessed by the proportion of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48. Participants who benefit from their assigned intervention (as determined by investigator) will be able to continue treatment through a 24-week study extension.

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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

St Vincent's Hospital ( Site 3807), Darlinghurst, 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 HIV-1 positive with plasma Human Immunodeficiency Virus 1 (HIV-1) RNA <50 copies/mL at screening.
  • Has been receiving bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) therapy 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 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 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 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

100 mg DOR/ 0.75 ISL FDC single tablet taken orally once daily

Other names: MK-8591A

BIC/FTC/TAF

Drug

50 mg BIC, 200 mg FTC, and 25 mg TAF combined in a single tablet, taken orally once daily

Placebo to BIC/FTC/TAF

Drug

Placebo to BIC/FTC/TAF in a single tablet taken orally, once daily

Placebo to FDC DOR/ISL

Drug

Placebo to FDC DOR/ISL in a single tablet taken orally, once daily

Other names: Placebo to MK-8591A

Primary outcomes

  1. Percentage of Participants With Human Immunodeficiency Virus 1 Ribonucleic Acid (HIV-1 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. Per protocol, the primary outcome measure, the percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48, is presented using the Food and Drug Administration (FDA) Snapshot missing data approach. The percentage values were rounded to the nearest tenth digit.

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

    Time frame: Up to 48 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 intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who experienced an AE up to week 48 is presented.

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

    Time frame: Up to 48 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 intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The percentage of participants who discontinued study intervention due to an AE up to week 48 is presented.

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. Per protocol, the secondary outcome measure, percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 96, is presented using the Food and Drug Administration (FDA) Snapshot missing data approach. The percentage values were rounded to the nearest tenth digit.

  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. Per protocol, the secondary outcome measure, percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 144, is presented using the FDA snapshot missing data approach. The percentage values were rounded to the nearest tenth digit.

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

    Time frame: Week 48

    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. Per protocol, the secondary outcome measure, the percentage of participants with HIV-1 RNA <50 copies/mL at Week 48, is presented using the FDA snapshot missing data approach. The percentage values were rounded to the nearest tenth digit.

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

    Time frame: Week 48

    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. Per protocol, the secondary outcome measure, the percentage of participants with HIV-1 RNA <40 copies/mL at Week 48, 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

    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. Per protocol, the secondary outcome measure, the percentage of participants with HIV-1 RNA <50 copies/mL at Week 96, is presented using the FDA snapshot missing data approach. The percentage values were rounded to the nearest tenth digit.

  6. 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. Per protocol, the secondary outcome measure, the percentage of participants with HIV-1 RNA <40 copies/mL at Week 96, is presented using the FDA snapshot missing data approach.

  7. 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. Per protocol, the secondary outcome measure, the percentage of participants with HIV-1 RNA <50 copies/mL at Week 144 is presented using the FDA snapshot missing data approach. The percentage values were rounded to the nearest tenth digit.

  8. 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. Per protocol, the secondary outcome measure, percentage of participants with HIV-1 RNA <40 copies/mL at Week 144, is presented using the FDA snapshot missing data approach.

  9. Mean Change From Baseline in Cluster of Differentiation-positive (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 by a central laboratory. Baseline measurement of CD4+ T-cell count is defined as the day 1 value for each participant. The mean change from baseline in CD4+ T-cell count at week 48 using the data as observed (DAO) approach is presented. A negative value indicates a mean decrease in CD4+ T-cell count from baseline and a positive value indicates a mean increase in CD4+ T-cell count from baseline.

  10. Mean 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 by a central laboratory. Baseline measurement of CD4+ T-cell count is defined as the day 1 value for each participant. The mean change from baseline in CD4+ T-cell count at week 96 using the data as observed (DAO) approach is presented. A negative value indicates a mean decrease in CD4+ T-cell count from baseline and a positive value indicates a mean increase in CD4+ T-cell count from baseline.

  11. Mean Change From Baseline in CD4+ T-cell Count at Week 144

    Time frame: Baseline and Week 144

    Plasma CD4+ T-cell count was measured in cells/mm^3 for baseline and 144 weeks by a central laboratory. Baseline measurement of CD4+ T-cell count is defined as the day 1 value for each participant. The mean change from baseline in CD4+ T-cell count at week 144 using the data as observed (DAO) approach is presented. A negative value indicates a mean decrease in CD4+ T-cell count from baseline and a positive value indicates a mean increase in CD4+ T-cell count from baseline.

  12. Number of Participants With 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 having genotypic or phenotypic evidence of resistance to the study drug administered. The number of participants who demonstrate drug resistance is presented.

  13. Number of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 96

    Time frame: Week 96

    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 number of participants who demonstrate drug resistance at week 96 is presented.

  14. Number of Participants With Evidence of Viral Drug Resistance-associated Substitutions at Week 144

    Time frame: Week 144

    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 number of participants who demonstrate drug resistance at week 144 is presented.

  15. Change From Baseline in Body Weight at Week 48

    Time frame: Baseline and Week 48

    Body weight was measured and recorded at baseline and week 48. Participants removed their shoes and wore a single layer of clothing at each measurement. The mean change from baseline in body weight at week 48 is presented.

  16. Change From Baseline in Body Weight at Week 96

    Time frame: Baseline and Week 96

    Body weight was measured and recorded at baseline and week 96. Participants removed their shoes and wore a single layer of clothing at each measurement. The mean change from baseline in body weight at week 96 is presented.

  17. Change From Baseline in Body Weight at Week 144

    Time frame: Baseline and Week 144

    Body weight was measured and recorded at baseline and week 144. Participants removed their shoes and wore a single layer of clothing at each measurement. The mean change from baseline in body weight at week 144 is presented.

  18. Percentage of Participants With One or More AEs

    Time frame: Up to approximately 55 months

    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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. 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.

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

    Time frame: Up to approximately 40 months

    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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. 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.

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) Once-Daily in Participants With HIV-1 Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF)

Important dates

Study start
2020
Primary completion
2021
Study completion
2025
First posted
Jan 10, 2020
Registry last updated
Mar 27, 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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