Safety and Efficacy of Doravirine, Tenofovir, Lamivudine (MK-1439A) in Participants Infected With Treatment-Naïve Human Immunodeficiency Virus (HIV) -1 With Transmitted Resistance (MK-1439A-030)

Study Overview
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Brief Summary
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The primary objectives of this study are to evaluate the antiretroviral activity and the safety/tolerability of open-label doravirine/lamivudine/tenofovir disoproxil fumarate (DOR/3TC/TDF; MK-1439A; DELSTRIGO™) consisting of a single fixed-dose combination (FDC) tablet of DOR/3TC/TDF 100 mg/300 mg/300 mg in treatment-naïve HIV-1 infected participants with select non-nucleoside reverse transcriptase inhibitor (NNRTI) transmitted resistance-associated mutations.

Detailed Description
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This study had a Base Study (Day 1 to Week 96) and an optional Study Extension (Week 96 to Week 192).

Official Title
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A Phase IIa Multicenter, Open-Label Clinical Trial to Evaluate the Safety and Efficacy of MK-1439A in Treatment-Naïve HIV-1 Infected Subjects With Selected Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) Transmitted Resistance Mutations

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: Doravirine/lamivudine/tenofovir disoproxil fumarate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is HIV-1 positive within 45 days prior to the treatment phase of this study, and have HIV treatment indicated based on physician assessment. Is naïve to antiretroviral therapy (ART) including investigational antiretroviral agents. Prior to screening, have had a genotype performed confirming the presence of only one of the following NNRTI mutations: K103N, Y181C, or G190A. Is considered clinically stable with no signs or symptoms of active infection at time of entry into the study (i.e. clinical status and all chronic medications should be unchanged for at least 2 weeks prior to the start of treatment in this study). Is highly unlikely to become pregnant or to impregnate a partner Exclusion Criteria: Is a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence. Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1, including, but not limited to, adefovir, tenofovir, entecavir, emtricitabine, or lamivudine. Has documented or known resistance to study drugs (doravirine, lamivudine, and/or tenofovir) Has participated or anticipates participating in a study with an investigational compound/device within 30 days prior to signing informed consent Has any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids, tumor necrosis factor (TNF) antagonists, or other immunosuppressant drugs during the course of the trial. Requires or anticipates requiring any of the prohibited medications Has significant hypersensitivity or other contraindication to any of the components of the study drug Has a current (active) diagnosis of acute hepatitis due to any cause Has evidence of decompensated liver disease or has liver cirrhosis and a Child-Pugh Class C score or Pugh-Turcotte (CPT) score > 9 Is pregnant, breastfeeding, or expecting to conceive Is female and expecting to donate eggs, or is male and is expecting to donate sperm at any time during the study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DOR/3TC/TDF<br>Treatment-naïve HIV-1 infected participants with NNRTI transmitted resistance-associated mutations were treated with open-label MK-1439A (DOR/3TC/TDF 100mg/300mg/300mg) as a FDC tablet taken once daily by mouth for 96 weeks in the Base Study. In addition, eligible participants continued to receive the same MK-1439A regimen from Week 96 to Week 192 during the Extension Study. | Drug: Doravirine/lamivudine/tenofovir disoproxil fumarate<br>* FDC tablet containing MK-1439 (doravirine) 100 mg / lamivudine 300 mg / tenofovir disoproxil fumarate 300 mg taken by mouth.<br>* Other names: DELSTRIGO™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL of Plasma at Week 48 | The percentage of participants achieving HIV-1 ribonucleic acid (RNA) <50 copies/mL in plasma at Week 48 was calculated. The Abbott RealTime HIV-1 Assay, which has a lower limit of reliable quantification (LoQ) of 40 copies/mL, was used to measure the HIV-1 RNA level in plasma samples obtained at Week 48 visit. | Week 48 | 
| Percentage of Participants Experiencing ≥1 Adverse Events (AE) up to Week 48 | The percentage of participants experiencing ≥1 AE up to Week 48 was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined. | Up to Week 48 | 
| Percentage of Participants Who Discontinued Treatment Due to an AE up to Week 48. | The percentage of participants who discontinued from study medication due to an adverse event was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined. | Up to Week 48 | 
| Percentage of Participants Experiencing ≥1 Adverse Events (AE) up to Week 96 | The percentage of participants experiencing ≥1 AE up to Week 96 was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined. | Up to Week 96 | 
| Percentage of Participants Who Discontinued Treatment Due to an AE up to Week 96 | The percentage of participants who discontinued from study medication due to an adverse event was calculated. An AE was defined as any unfavorable and unintended sign, symptom, or disease (new or worsening) temporally associated with the use of study therapy, regardless of whether or not a causal relationship with the study therapy could be determined. | Up to Week 96 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL of Plasma at Week 96 | The percentage of participants achieving HIV-1 ribonucleic acid (RNA) <50 copies/mL in plasma at Week 96 was calculated. The Abbott RealTime HIV-1 Assay, which has a lower limit of reliable quantification (LoQ) of 40 copies/mL, was used to measure the HIV-1 RNA level in plasma samples obtained at Week 96 visit. | Week 96 | 
| Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <40 Copies/mL of Plasma at Week 48 | The percentage of participants achieving HIV-1 ribonucleic acid (RNA) <40 copies/mL in plasma at Week 48 was calculated. The Abbott RealTime HIV-1 Assay, which has a lower limit of reliable quantification (LoQ) of 40 copies/mL, was used to measure the HIV-1 RNA level in plasma samples obtained at Week 48 visit. Participants with reading below the LoQ were considered to have <40 copies/mL. | Week 48 | 
| Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <40 Copies/mL of Plasma at Week 96 | The percentage of participants achieving HIV-1 ribonucleic acid (RNA) <40 copies/mL in plasma at Week 96 was calculated. The Abbott RealTime HIV-1 Assay, which has a lower limit of reliable quantification (LoQ) of 40 copies/mL, was used to measure the HIV-1 RNA level in plasma samples obtained at Week 96 visit. Participants with reading below the LoQ were considered to have <40 copies/mL. | Week 96 | 
| Change From Baseline in CD4 Cell Count at Week 48 | The change from baseline in CD4 cell count at Week 48 was calculated. | Baseline (Day 1) and Week 48 | 
| Change From Baseline in CD4 Cell Count at Week 96 | The change from baseline in CD4 cell count at Week 96 was calculated. | Baseline (Day 1) and Week 96 | 
| Time to Loss of Virologic Response | The time to loss of virologic response (TLOVR) was reported. For participants who achieved HIV-1 RNA <50 copies/mL of plasma and subsequently had two consecutive HIV-1 RNA values of ≥50 copies/mL measured at least 1 week apart, TLOVR was the time between Day 1 and the date of the first of the two consecutive values ≥50 copies/mL. For participants who achieved and sustained HIV-1 RNA <50 copies/mL, time to loss of virologic response was censored at the time of the last available measurement. | Up to Week 96 |