Phase 3
Completed N=769
Safety and Efficacy of Doravirine (MK-1439) in Participants With Human Immunodeficiency Virus 1 (HIV-1) (MK-1439-018)
Source: ClinicalTrials.gov NCT02275780 ↗Enrolled (actual)
769
Serious AEs
12.3%
Results posted
Oct 2018
Primary outcomePrimary: Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 48 — 83.8; 79.9 Percentage of participants
◆ Published Evidence
Established
30citations · ~15 / year
Safety and efficacy of doravirine as first-line therapy in adults with HIV-1: week 192 results from the open-label extensions of the DRIVE-FORWARD and DRIVE-AHEAD phase 3 trials.
Summary
To establish a new treatment option for treatment-naïve participants with HIV-1, the efficacy and safety of doravirine will be determined relative to a protease inhibitor (PI). Participants will receive double-blind treatment during the 96-week Base Study. Eligible participants in either of the Base Study groups will continue to receive the doravirine-containing regimen open label for an additional 96 weeks in the Study Extension 1. Eligible participants who are deriving benefit will continue in Study Extension 2 to receive the doravirine-containing regimen open label until doravirine becomes locally available or for an additional 96 weeks, whichever comes first. The primary hypothesis is that doravirine 100 mg once a day (q.d.) is non-inferior to darunavir/ritonavir (800 mg/100 mg) q.d., each in combination with TRUVADA™ or EPZICOM™/KIVEXA™, as assessed by the proportion of participants with HIV-1 ribonucleic acid (RNA) <50 copies/mL at Week 48. If non-inferiority is established, then the superiority of doravirine 100 mg q.d. compared to darunavir/ ritonavir (800 mg/100 mg) q.d. will be assessed.
Linked Publications (5)
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Safety and efficacy of doravirine as first-line therapy in adults with HIV-1: week 192 results from the open-label extensions of the DRIVE-FORWARD and DRIVE-AHEAD phase 3 trials.
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Brief Report: Resolution of Neuropsychiatric Adverse Events After Switching to a Doravirine-Based Regimen in the Open-Label Extensions of the DRIVE-AHEAD and DRIVE-FORWARD Trials.
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Factors Associated With Weight Change After Continuing or Switching to a Doravirine-based Regimen.
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Cardiovascular Risk Assessment Using the Atherosclerotic Cardiovascular Disease Risk Score Model after Continuing or Switching to a Doravirine-Based HIV Treatment Regimen.
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Efficacy and Safety of Doravirine-based Regimens by Sex and Race: Long-term Results From Three Phase 3 Clinical Trials.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 48 |
83.8; 79.9 | — |
| SECONDARY Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 96 |
73.1; 66.0 | — |
| SECONDARY Change From Baseline in Mean CD4+ T-cell Count at Week 48 |
192.7; 185.6 | — |
| SECONDARY Change From Baseline in Mean CD4+ T-cell Count at Week 96 |
224.1; 206.7 | — |
| SECONDARY Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48 |
91.10; 91.76; -4.51; 9.92 | <0.0001 sig |
| SECONDARY Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48 |
113.34; 114.44; -5.30; 13.75 | <0.0001 sig |
| SECONDARY Mean Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 48 |
43.58; 43.27; 3.94; 4.15 | — |
| SECONDARY Mean Change From Baseline in Fasting Total Cholesterol at Week 48 |
156.92; 157.71; -1.37; 17.90 | — |
| SECONDARY Mean Change From Baseline in Fasting Triglyceride at Week 48 |
111.16; 117.02; -3.14; 21.97 | — |
| SECONDARY Percentage of Participants With Any Adverse Event |
84.6; 82.8 | — |
| SECONDARY Percentage of Participants With Any Serious Adverse Event |
7.0; 8.6 | — |
| SECONDARY Percentage of Participants With Any Drug-related Adverse Event |
32.1; 32.1 | — |
| SECONDARY Percentage of Participants With Any Drug-related Serious Adverse Event |
0.3; 0.3 | — |
| SECONDARY Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event |
1.6; 3.4 | — |
| SECONDARY Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 48 |
83.3; 79.1 | — |
| SECONDARY Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 96 |
72.0; 64.4 | — |
Eligibility Criteria
Inclusion Criteria
- Is HIV-1 positive and has HIV treatment indicated based on physician assessment.
- Has received no (0 days of) antiretroviral therapy (ART), including investigational antiretroviral agents.
- Is considered clinically stable with no signs or symptoms of active infection for at least 2 weeks prior to the start of treatment.
- Female is highly unlikely to become pregnant, or male is highly unlikely to impregnate a partner because they are not of reproductive potential, or agree to practice abstinence or use acceptable contraception for up to 14 days after the last dose of study drug.
- Eligibility for the Study Extension 1 at the Week 96 visit: 1) completed the Week 96 visit, 2) derived benefit from participation through Week 96 in the opinion of the investigator, 3) is a clinically-appropriate candidate for an additional 96 weeks of treatment with the Study Extension regimen.
- Eligibility for the Study Extension 2 at the Week 192 visit: 1) completed the Week 192 visit, 2) derived benefit from participation through Week 192 in the opinion of the investigator, 3) is a clinically-appropriate candidate for 96 weeks of treatment with the Study Extension regimen.
Exclusion Criteria
- Uses or has had a recent history of using recreational or illicit drugs.
- Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1.
- Has documented or known resistance to study drugs including doravirine, darunavir, ritonavir, emtricitabine, tenofovir, abacavir and/or lamivudine.
- Has participated in a study with an investigational compound/device within the prior month, or anticipates doing so during this study.
- Has used systemic immunosuppressive therapy or immune modulators within the prior 30 days, or anticipates doing so during this study.
- Has significant hypersensitivity or other contraindication to any of the components of the study drugs.
- Has a current (active) diagnosis of acute hepatitis due to any cause.
- Is pregnant, breastfeeding or expecting to conceive at any time during the study.
- Female who expects to donate eggs, or male who expects to donate sperm at any time during the study.
Data sourced from ClinicalTrials.gov (NCT02275780) and the linked publication. 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. Informational only — not medical advice.