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)

Phase 3

Active, not recruiting

• Conditions: HIV-1 Infection
• Interventions: Drug: DOR/ISL; Drug: BIC/FTC/TAF; Drug: Placebo to BIC/FTC/TAF; Drug: Placebo to DOR/ISL

• Registration Number: NCT05630755
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-11-18
• Study First Submitted QC: 2022-11-18
• Study First Posted: 2022-11-30
• Study Start: 2023-02-17
• Primary Completion: 2024-10-25
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-06
• Last Update Posted: 2024-11-07
• Study Completion: 2028-08-04

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 514

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DOR/ISL and Placebo to BIC/FTC/TAF	DOR/ISL	Participants will receive DOR/ISL 100 mg/0.25 mg and Placebo to BIC/FTC/TAF once daily (QD) orally from day 1 to week 144. After week 144, eligible participants may continue on DOR/ISL and continue study treatment until week 240 or to when DOR/ISL becomes commercially accessible (whichever comes first).
DOR/ISL and Placebo to BIC/FTC/TAF	Placebo to BIC/FTC/TAF	Participants will receive DOR/ISL 100 mg/0.25 mg and Placebo to BIC/FTC/TAF once daily (QD) orally from day 1 to week 144. After week 144, eligible participants may continue on DOR/ISL and continue study treatment until week 240 or to when DOR/ISL becomes commercially accessible (whichever comes first).
BIC/FTC/TAF and Placebo to DOR/ISL	BIC/FTC/TAF	Participants will receive BIC/FTC/TAF 50 mg/200 mg/25 mg and Placebo to DOR/ISL once daily (QD) orally from day 1 to week 144. After week 144, eligible participants may switch to DOR/ISL and continue study treatment until week 240 or to when DOR/ISL becomes commercially accessible (whichever comes first).
BIC/FTC/TAF and Placebo to DOR/ISL	Placebo to DOR/ISL	Participants will receive BIC/FTC/TAF 50 mg/200 mg/25 mg and Placebo to DOR/ISL once daily (QD) orally from day 1 to week 144. After week 144, eligible participants may switch to DOR/ISL and continue study treatment until week 240 or to when DOR/ISL becomes commercially accessible (whichever comes first).

Primary Outcome Measures

Name	Time	Method
Percentage of participants who experience adverse events (AEs) through Week 48	Up to Week 48	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.
Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48	Week 48	Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 48 will be reported.
Percentage of participants who discontinue study intervention due to AEs through Week 48	Up to Week 48	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of participants with HIV-1 RNA <200 copies/mL at Week 48	Week 48	Percentage of participants with HIV-1 RNA \<200 copies/mL at Week 48 will be reported.
Change from baseline in CD4+ T-cell count at Week 96	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.
Percentage of participants with HIV-1 RNA <200 copies/mL at Week 96	Week 96	Percentage of participants with HIV-1 RNA \<200 copies/mL at Week 96 will be reported.
Percentage of participants with HIV-1 RNA <200 copies/mL at Week 144	Week 144	Percentage of participants with HIV-1 RNA \<200 copies/mL at Week 144 will be reported.
Change from baseline in CD4+ T-cell count at Week 48	Baseline at Day 1 and Week 48	Mean change from baseline at Day 1 in CD4+ T-cell count at Week 48 will be reported.
Number of participants with viral drug resistance mutations at Week 96	Week 96	Number of participants with evidence of viral drug resistance-associated substitutions at Week 96 will be reported.
Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 96	Week 96	Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 96 will be reported.
Percentage of participants with HIV-1 RNA <50 copies/mL at Week 96	Week 96	Percentage of participants with HIV-1 RNA \<50 copies/mL at Week 96 will be reported.
Percentage of participants with HIV-1 RNA <50 copies/mL at Week 48	Week 48	Percentage of participants with HIV-1 RNA \<50 copies/mL at Week 48 will be reported.
Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 144	Week 144	Percentage of participants with HIV-1 RNA ≥50 copies/mL at Week 144 will be reported.
Percentage of participants with HIV-1 RNA <50 copies/mL at Week 144	Week 144	Percentage of participants with HIV-1 RNA \<50 copies/mL at Week 144 will be reported.
Number of participants with viral drug resistance mutations at Week 48	Week 48	Number of participants with evidence of viral drug resistance-associated substitutions at Week 48 will be reported.
Percentage of participants who experience AEs through Week 144	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.
Change from baseline in CD4+ T-cell count at Week 144	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.
Number of participants with viral drug resistance mutations at Week 144	Week 144	Number of participants with evidence of viral drug resistance-associated substitutions at Week 144 will be reported.
Percentage of participants who discontinue study intervention due to AEs through Week 144	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.

Trial Locations

Locations (49)

Pueblo Family Physicians ( Site 1425); 🇺🇸 Phoenix, Arizona, United States

Pacific Oaks Medical Group ( Site 1400); 🇺🇸 Beverly Hills, California, United States

Ruane Clinical Research Group, Inc ( Site 1414); 🇺🇸 Los Angeles, California, United States

Mills Clinical Research ( Site 1433); 🇺🇸 Los Angeles, California, United States

Whitman-Walker Institute ( Site 1431); 🇺🇸 Washington, District of Columbia, United States

Therafirst Medical Center ( Site 1402); 🇺🇸 Fort Lauderdale, Florida, United States

Midway Immunology and Research Center ( Site 1401); 🇺🇸 Fort Pierce, Florida, United States

AHF The Kinder Medical Group ( Site 1426); 🇺🇸 Miami, Florida, United States

Orlando Immunology Center ( Site 1407); 🇺🇸 Orlando, Florida, United States

Triple O Research Institute, P.A ( Site 1417); 🇺🇸 West Palm Beach, Florida, United States

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