Phase 3
N=35
Doravirine/Islatravir (DOR/ISL) in Heavily Treatment-Experienced (HTE) Participants for Human Immunodeficiency Virus Type 1 (HIV-1) Infection (MK-8591A-019)
HIV-1 Infection
Bottom Line
View on ClinicalTrials.gov: NCT04233216 ↗Enrolled (actual)
35
Serious AEs
17.1%
Results posted
Dec 2023
Primary outcome: Primary: Percentage of Participants Receiving Doravirine/Islatravir (DOR/ISL) With ≥0.5 log10 Change From Day 1 Baseline to Day 8 in Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Compared to Placebo Treatment — 85.7; 0.0 Percentage of participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- ISL (Drug); DOR (Drug); DOR/ISL (Drug); Placebo to ISL (Drug); Placebo to DOR (Drug)
- Age
- Pediatric, Adult, Older Adult
- Sex
- All
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- Nov 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Receiving Doravirine/Islatravir (DOR/ISL) With ≥0.5 log10 Change From Day 1 Baseline to Day 8 in Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Compared to Placebo Treatment |
85.7; 0.0 | — |
| PRIMARY Percentage of Participants With ≥1 AEs Through Week 49 |
71.4; 85.7; 85.7; 85.7 | — |
| PRIMARY Percentage of Participants Withdrawing From Study Treatment Due to AE(s) Through Week 25 |
0.0; 7.1; 14.3; 0.0 | — |
| PRIMARY Percentage of Participants With ≥1 Adverse Events (AEs) Through Week 25 |
42.9; 85.7; 85.7; 85.7 | — |
| PRIMARY Percentage of Participants Withdrawing From Study Treatment Due to AE(s) Through Week 49 |
0.0; 14.3; 14.3; 0.0 | — |
| SECONDARY Percentage of Participants With ≥1 Adverse Events (AEs) Through Week 97 |
85.7; 100.0; 85.7; 100.0 | — |
| SECONDARY Percentage of Participants Discontinuing From Study Therapy Due to AE(s) Through Week 97 |
0.0; 21.4; 28.6; 14.3 | — |
| SECONDARY Percentage of Participants Receiving DOR or ISL (Given With Antiretroviral Therapy [ART]) With ≥0.5 log10 Change From Day 1 Baseline to Day 8 HIV-1 RNA Compared to Placebo Treatment |
28.6; 78.6; 0.0 | — |
| SECONDARY Mean Change From Baseline Day 1 to Day 8 in HIV-1 RNA Following Treatment With DOR/ISL (Given With ART), DOR, or ISL Compared to Placebo Treatment |
-0.44; -0.96; -1.23; 0.03 | — |
| SECONDARY Percentage of Participants Receiving DOR/ISL (Given With ART), DOR, or ISL With ≥1.0 log10 Change From Day 1 Baseline to Day 8 HIV-1 RNA Compared to Placebo Treatment |
14.3; 50.0; 85.7; 0.0 | — |
| SECONDARY Percentage of Participants Receiving DOR/ISL (Given With ART) With ≥0.5 log10 Change From Day 1 Baseline to Day 8 in HIV-1 RNA Compared to DOR or ISL Treatment |
28.6; 78.6; 85.7 | — |
| SECONDARY Mean Change From Baseline Day 1 to Day 8 in HIV-1 RNA Following Treatment With DOR/ISL (Given With ART) Compared to DOR or ISL Treatment |
-0.44; -0.96; -1.23 | — |
| SECONDARY Percentage of Participants Receiving DOR/ISL (Given With ART) With ≥1.0 log10 Change From Day 1 Baseline to Day 8 in HIV-1 RNA Compared to DOR or ISL Treatment |
14.3; 50.0; 85.7 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With ≥0.5 log10 Change From Day 1 Baseline to Week 25 in HIV-1 RNA |
85.3 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With ≥0.5 log10 Change From Day 1 Baseline to Week 49 in HIV-1 RNA |
80.6 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With ≥0.5 log10 Change From Day 1 Baseline to Week 97 in HIV-1 RNA |
84.6 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With ≥0.5 log10 Change From Day 8 Baseline to Week 25 in HIV-1 RNA |
64.7 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With ≥0.5 log10 Change From Day 8 Baseline to Week 49 in HIV-1 RNA |
67.7 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With ≥0.5 log10 Change From Day 8 Baseline to Week 97 in HIV-1 RNA |
69.2 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With ≥1.0 log10 Change From Day 1 Baseline to Week 25 in HIV-1 RNA |
67.6 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With ≥1.0 log10 Change From Day 1 Baseline to Week 49 in HIV-1 RNA |
71.0 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With ≥1.0 log10 Change From Day 1 Baseline to Week 97 in HIV-1 RNA |
73.1 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With ≥1.0 log10 Change From Day 8 Baseline to Week 25 in HIV-1 RNA |
58.8 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With ≥1.0 log10 Change From Day 8 Baseline to Week 49 in HIV-1 RNA |
61.3 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With ≥1.0 log10 Change From Day 8 Baseline to Week 97 in HIV-1 RNA |
61.5 | — |
| SECONDARY Mean Change From Baseline Day 1 to Week 25 in HIV-1 RNA From the Pooled Treatment Group |
-1.89 | — |
| SECONDARY Mean Change From Baseline Day 1 to Week 49 in HIV-1 RNA From the Pooled Treatment Group |
-2.00 | — |
| SECONDARY Mean Change From Baseline Day 1 to Week 97 in HIV-1 RNA From the Pooled Treatment Group |
-2.01 | — |
| SECONDARY Mean Change From Baseline Day 8 to Week 25 in HIV-1 RNA From the Pooled Treatment Group |
-1.16 | — |
| SECONDARY Mean Change From Baseline Day 8 to Week 49 in HIV-1 RNA From the Pooled Treatment Group |
-1.32 | — |
| SECONDARY Mean Change From Baseline Day 8 to Week 97 in HIV-1 RNA From the Pooled Treatment Group |
-1.36 | — |
| SECONDARY Percentage of Participants From Day 1 Baseline to Day 8 With HIV-1 RNA <200 Copies mL |
0.0; 0.0; 0.0; 0.0; 0.0; 14.3 | — |
| SECONDARY Percentage of Participants From Day 1 Baseline to Day 8 With HIV-1 RNA <50 Copies mL |
0.0; 0.0; 0.0; 0.0; 0.0; 14.3 | — |
| SECONDARY Percentage of Participants From Day 1 Baseline to Day 8 With HIV-1 RNA <40 Copies mL |
0.0; 0.0; 0.0; 0.0; 0.0; 14.3 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <200 Copies/mL at Week 25 |
64.7 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <200 Copies/mL at Week 49 |
77.4 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <200 Copies/mL at Week 97 |
80.8 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <50 Copies/mL at Week 25 |
58.8 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <50 Copies/mL at Week 49 |
71.0 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <50 Copies/mL at Week 97 |
69.2 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <40 Copies/mL at Week 25 |
58.8 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <40 Copies/mL at Week 49 |
71.0 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With HIV-1 RNA <40 Copies/mL at Week 97 |
69.2 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With Treatment-emergent Resistance-associated Substitutions to DOR at Week 25 |
33.3 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With Treatment-emergent Resistance-associated Substitutions to DOR at Week 49 |
28.6 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With Treatment-emergent Resistance-associated Substitutions to ISL at Week 25 |
8.3 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With Treatment-emergent Resistance-associated Substitutions to ISL at Week 49 |
14.3 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With Treatment-emergent Resistance-associated Substitutions to Optimized Background Therapy (OBT) Components at Week 25 |
25.0 | — |
| SECONDARY Percentage of Participants From the Pooled Treatment Group With Treatment-emergent Resistance-associated Substitutions to OBT Components at Week 49 |
28.6 | — |
| SECONDARY Number of Participants From the Pooled Treatment Group With Viral Resistance-associated Substitutions (RASs) at Week 25 |
2; 1; 1; 1; 1; 1 | — |
| SECONDARY Number of Participants From the Pooled Treatment Group With Viral RASs at Week 49 |
1; 1; 1; 1; 1; 1 | — |
| SECONDARY Number of Participants From the Pooled Treatment Group With Viral RASs at Week 97 |
1; 1; 1; 1; 2; 1 | — |
| SECONDARY Number of Participants From the Pooled Treatment Group Exhibiting Antiviral Resistance of HIV-1 RNA ≥200 Copies/mL at Week 25 |
12 | — |
| SECONDARY Number of Participants From the Pooled Treatment Group Exhibiting Antiviral Resistance of HIV-1 RNA ≥200 Copies/mL at Week 49 |
7 | — |
| SECONDARY Number of Participants From the Pooled Treatment Group Exhibiting Antiviral Resistance of HIV-1 RNA ≥200 Copies/mL at Week 97 |
5 | — |
| SECONDARY Change From Baseline Day 1 to Week 25 in Cluster of Differentiation 4+ (CD4+) T-cell Counts From the Pooled Treatment Group |
50.3 | — |
| SECONDARY Change From Baseline Day 1 to Week 49 in CD4+ T-cell Counts From the Pooled Treatment Group |
86.9 | — |
| SECONDARY Change From Baseline Day 1 to Week 97 in CD4+ T-cell Counts From the Pooled Treatment Group |
114.6 | — |
| SECONDARY Change From Baseline Day 8 to Week 25 in CD4+ T-cell Counts From the Pooled Treatment Group |
38.0 | — |
| SECONDARY Change From Baseline Day 8 to Week 49 in CD4+ T-cell Counts From the Pooled Treatment Group |
75.1 | — |
| SECONDARY Change From Baseline Day 8 to Week 97 in CD4+ T-cell Counts From the Pooled Treatment Group |
108.0 | — |
Summary
This is a 2-part, phase 3 clinical study evaluating the antiretroviral activity and safety/tolerability of islatravir (ISL), doravirine (DOR), and a fixed dose combination (FDC) of DOR/ISL (also known as MK-8591A) in heavily treatment-experienced (HTE) participants with human immunodeficiency virus type 1 (HIV-1) infection. It is hypothesized that the percentage of participants receiving DOR/ISL to achieve ≥0.5 log10 decrease in HIV-1 ribonucleic acid (RNA) from study baseline (Day 1) to Day 8 is superior to placebo, each given in combination with failing antiretroviral therapy (ART).
Eligibility Criteria
Inclusion Criteria
- Is HIV-1 positive.
- Has been receiving the same baseline ART for ≥3 months prior to signing the Informed Consent Form/Assent Form.
- Weighs ≥35 kg.
- Has at least triple-class resistance (must include nucleoside reverse transcriptase inhibitor [NRTI], non-nucleoside reverse transcriptase inhibitor [NNRTI], and resistance to either protease inhibitor (PI) or integrase strand transfer inhibitor (InSTI), based on central laboratory-based resistance or proviral DNA resistance testing at the Screening Visit, or historical resistance testing within 12 months of screening.
- Has ≤2 fully active antiretroviral drugs remaining among all antiretroviral classes that can be effectively combined to form a viable regimen based on resistance, tolerability, safety, drug access, or acceptability to participant.
- If female, is not pregnant or breastfeeding, and is: 1) not a woman of childbearing potential (WOCBP); 2) a WOCBP and uses an acceptable method of contraception/is abstinent; or 3) a WOCBP and has a negative pregnancy test within 24 hours of the first dose of study medication.
Exclusion Criteria
- Has HIV type 2 (HIV-2) infection.
- Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator.
- Has hepatitis B virus (HBV) co-infection (defined as hepatitis B surface antigen [HBsAg]-positive or HBV deoxyribonucleic acid [DNA] positive) and is not currently being treated for HBV.
- Has a history or current evidence of any condition, therapy (including active TB co-infection), laboratory abnormality or other circumstance (including drug or alcohol abuse or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with study participation for the full study duration.
- Is taking or is anticipated to require any of the prohibited therapies from the Screening Visit and throughout the study treatment period.
- Is taking DOR as part of his/her current failing antiretroviral regimen.
- Is taking efavirenz (EFV), etravirine, or nevirapine.
- Is currently participating in or has participated in an interventional clinical study with an investigational compound or device from the Screening Visit through the study treatment period.
- Is female and is expecting to conceive or donate eggs at any time during the study.
Data sourced from ClinicalTrials.gov (NCT04233216). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.