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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 10
- 主要终点
- Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL of Plasma at Week 48
研究概览
简要总结
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.
详细描述
This study had a Base Study (Day 1 to Week 96) and an optional Study Extension (Week 96 to Week 192).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
DOR/3TC/TDF
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.
干预措施: Doravirine/lamivudine/tenofovir disoproxil fumarate (Drug)
结局指标
主要结局
Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL of Plasma at Week 48
时间窗: 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.
Percentage of Participants Experiencing ≥1 Adverse Events (AE) up to Week 96
时间窗: 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.
Percentage of Participants Who Discontinued Treatment Due to an AE up to Week 96
时间窗: 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.
Percentage of Participants Experiencing ≥1 Adverse Events (AE) up to Week 48
时间窗: 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.
Percentage of Participants Who Discontinued Treatment Due to an AE up to Week 48.
时间窗: 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.
次要结局
- Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <40 Copies/mL of Plasma at Week 96(Week 96)
- Change From Baseline in CD4 Cell Count at Week 48(Baseline (Day 1) and Week 48)
- Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL of Plasma at Week 96(Week 96)
- Percentage of Participants Achieving HIV-1 Ribonucleic Acid (RNA) <40 Copies/mL of Plasma at Week 48(Week 48)
- Change From Baseline in CD4 Cell Count at Week 96(Baseline (Day 1) and Week 96)
- Time to Loss of Virologic Response(Up to Week 96)