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)

Phase 3

Active, not recruiting

• Conditions: HIV-1 Infection
• Interventions: Drug: DOR/ISL; Drug: ART

• Registration Number: NCT05631093
• Lead Sponsor: Merck Sharp & Dohme LLC

Brief Summary

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.

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: 2023-02-20
• Primary Completion: 2024-10-10
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-07
• Last Update Posted: 2024-11-08
• Study Completion: 2028-07-11

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 553

Inclusion Criteria

• Is HIV-1 positive with plasma HIV-1 RNA <50 copies/mL at screening
• Has been receiving continuous, stable oral 2-drug or 3-drug combination (± PK booster) 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 DOR

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
DOR/ISL	DOR/ISL	Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months on a stable oral ART are treated with DOR/ISL for 144 weeks. Participants will have the option to continue in an optional study extension and receive DOR/ISL for up to an additional 96 weeks or until DOR/ISL is commercially accessible (whichever comes first).
ART + DOR/ISL	ART	Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months on a stable oral ART are first treated with standard of care (SOC) ART for 48 weeks, followed by 96 weeks of treatment with DOR/ISL Participants will have the option to continue in an optional study extension and receive DOR/ISL for up to an additional 96 weeks or until DOR/ISL is commercially accessible (whichever comes first).
ART + DOR/ISL	DOR/ISL	Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months on a stable oral ART are first treated with standard of care (SOC) ART for 48 weeks, followed by 96 weeks of treatment with DOR/ISL Participants will have the option to continue in an optional study extension and receive DOR/ISL for up to an additional 96 weeks or until DOR/ISL is commercially accessible (whichever comes first).

Primary Outcome Measures

Name	Time	Method
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
Participants with one or more AEs at Week 48	Up to Week 48	Percentage of participants with one or more AEs from Day 1 up to Week 48
Participants with an AE leading to discontinuation of study intervention at Week 48	Up to Week 48	Percentage of participants with an AE leading to discontinuation of study intervention from Day 1 up to Week 48

Secondary Outcome Measures

Name	Time	Method
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
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
Change from Week 48 in CD4+ T-cell count at Week 144	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.
Low density lipoprotein cholesterol (LDL-C)	Baseline and Week 48	Mean change from Baseline to Week 48 in fasting LDL-C
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
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
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
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
Change from Day 1 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. This outcome measure is applicable to those randomized to start DOR/ISL on Day 1.
High density lipoprotein cholesterol (HDL-C)	Baseline and Week 48	Mean change from baseline to Week 48 in fasting HDL-C
Participants with one or more AEs at Week 96	Up to Week 96	Percentage of participants with one or more AEs from Day 1 up to Week 96
Participants with one or more AEs from Week 48 up to Week 144	Week 48 up to Week 144	Percentage of participants with one or more AEs from Week 48 up to Week 144
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
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
Change from Day 1 in cluster of differentiation 4+ (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
Participants with AEs leading to discontinuation of study intervention at Week 144	Up to Week 144	Percentage of participants with an AE leading to discontinuation of study intervention from Day 1 up to Week 144
Change from Day 1 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. This outcome measure is applicable to those randomized to start DOR/ISL on Day 1.
Participants with AEs leading to discontinuation of study intervention from Week 48 up to Week 144	Week 48 up to Week 144	Percentage of participants with an AE leading to discontinuation of study intervention from Week 48 up to Week 144
Change from Week 48 in CD4+ T-cell count at Week 96	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.
Participants with viral resistance-associated substitutions	Up to Week 144	Number of participants with viral resistance-associated substitutions
Participants with one or more AEs at Week 144	Up to Week 144	Percentage of participants with one or more AEs from Day 1 up to Week 144
Participants with AEs leading to discontinuation of study intervention at Week 96	Up to Week 96	Percentage of participants with an AE leading to discontinuation of study intervention from Day 1 up to Week 96
Participants with AEs leading to discontinuation of study intervention from Week 48 up to Week 96	Week 48 up to Week 96	Percentage of participants with an AE leading to discontinuation of study intervention from Week 48 up to Week 96
Participants with one or more AEs from Week 48 up to Week 96	Week 48 up to Week 96	Percentage of participants with one or more AEs from Week 48 up to Week 96

Trial Locations

Locations (53)

Kaiser Permanente-Infectious Disease ( Site 3014); 🇺🇸 Los Angeles, California, United States

Palmtree Clinical Research ( Site 3032); 🇺🇸 Palm Springs, California, United States

Zuckerberg San Francisco General Hospital and Trauma Center-UCSF ID Clinical Trials Center ( Site 30; 🇺🇸 San Francisco, California, United States

Georgetown University Medical Center ( Site 3006); 🇺🇸 Washington, District of Columbia, United States

Midway Immunology and Research Center ( Site 3009); 🇺🇸 Fort Pierce, Florida, United States

Orlando Immunology Center ( Site 3004); 🇺🇸 Orlando, Florida, United States

CAN Community Health - Sarasota ( Site 3017); 🇺🇸 Sarasota, Florida, United States

Triple O Research Institute, P.A ( Site 3026); 🇺🇸 West Palm Beach, Florida, United States

Infectious Disease Specialists of Atlanta ( Site 3003); 🇺🇸 Decatur, Georgia, United States

Chatham County Health Department - Chatham CARE Center-Infectious Disease ( Site 3028); 🇺🇸 Savannah, Georgia, United States

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