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)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: ART + 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 48 weeks of treatment with DOR/ISL |
Drug: ART
Standard of care ART, per approved product list, taken orally
Drug: DOR/ISL
Combination of 100 mg doravirine (DOR) with 0.25 mg Islatravir (ISL) in tablet form, taken orally, once daily.
Other Names:
|
| Experimental: 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 96 weeks |
Drug: DOR/ISL
Combination of 100 mg doravirine (DOR) with 0.25 mg Islatravir (ISL) in tablet form, taken orally, once daily.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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
- 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 <50 copies/mL at Week 48 [Week 48]
Percentage of participants with HIV-1 RNA <50 copies/mL at Week 48
- 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
- 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
- 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
- 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
- Participants with viral resistance-associated substitutions [Up to Week 96]
Number of participants with viral resistance-associated substitutions
- Low density lipoprotein cholesterol (LDL-C) [Baseline and Week 48]
Mean change from Baseline to Week 48 in fasting LDL-C
- 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 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 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
- 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
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Is HIV-1 positive with plasma HIV-1 RNA <50 copies/mL at screening
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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
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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
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Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
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Has a diagnosis of an active acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 30 days prior to screening
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Has active hepatitis B virus (HBV) infection
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Has chronic hepatitis C virus (HCV) infection consistent with cirrhosis
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Has a ≤5 years prior history of malignancy
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Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or strong and moderate cytochrome P450 3A (CYP3A ) inducers
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Has taken long-acting HIV therapy at any time
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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
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Has a documented or known virologic resistance to DOR
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-051
- MK-8591A-051
- 2022-502127-22