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)
Study Details
Study Description
Brief Summary
The primary objectives of this study are to evaluate the antiretroviral activity of a switch to DOR/ISL compared with continued 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: DOR/ISL and 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 96. |
Drug: DOR/ISL
DOR/ISL 100 mg/0.25 mg oral tablets once daily
Other Names:
Drug: Placebo to BIC/FTC/TAF
0 mg oral tablets once daily
|
| Active Comparator: BIC/FTC/TAF and 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 96. |
Drug: BIC/FTC/TAF
BIC/FTC/TAF 50 mg/200 mg/25 mg oral tablets once daily
Drug: Placebo to DOR/ISL
0 mg oral tablets once daily
|
Outcome Measures
Primary Outcome Measures
- 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 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 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
- 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 <200 copies/mL at Week 48 [Week 48]
Percentage of participants with HIV-1 RNA <200 copies/mL at Week 48 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 <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 <50 copies/mL at Week 96 [Week 96]
Percentage of participants with HIV-1 RNA <50 copies/mL at Week 96 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.
- 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.
- 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.
- 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 who experience AEs through study duration [Up to Week 102]
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 who discontinue study intervention due to AEs through study duration [Up to Week 96]
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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 8591A-052
- MK-8591A-052
- 2022-502079-49-00