A Phase 3 Randomized, Active-Controlled, Double-Blind Clinical Study to Evaluate the Antiretroviral Activity, Safety, and Tolerability of Doravirine/Islatravir Once-Daily in HIV-1 Infected Treatment-Naïve Participants
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 599
- 试验地点
- 95
- 主要终点
- Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48
研究概览
简要总结
This is a phase 3, randomized, controlled, double-blind, multisite clinical study of a once-daily fixed dose combination (FDC) of 100 mg doravirine/0.75 mg islatravir (DOR/ISL [also known as MK-8591A]) in treatment-naïve participants living with human immunodeficiency virus type-1 (HIV-1) infection. The primary objectives are to evaluate the antiretroviral activity, safety, and tolerability of DOR/ISL compared to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). The primary hypothesis is that DOR/ISL is noninferior or superior to BIC/FTC/TAF treatment based on the percentage of participants with HIV-1 ribonucleic acid (RNA) <50 copies/mL at Week 48.
详细描述
Double-blind treatment with the assigned intervention occurs from Day 1 to Week 96, followed by an open-label portion up to Week 144. Participants who benefit from treatment in the opinion of the Investigator may continue their assigned intervention up to Week 168 (or until they have the option to enroll in a DOR/ISL 100 mg/0.25 mg study, whichever is sooner).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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 human immunodeficiency virus type 1 (HIV-1) positive
- •Is naïve to antiretroviral therapy (ART) defined as having received ≤10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection including prevention of mother-to-child transmission up to 1 month prior to screening.
- •A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: 1) Is not a woman of childbearing potential (WOCBP); 2) Is a WOCBP and using an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis); 3) A WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 24 hours before the first dose of study intervention; 4) If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required
排除标准
- •Has human immunodeficiency virus 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 an active diagnosis of hepatitis due to any cause, including active hepatitis B virus (HBV) infection (defined as hepatitis B surface antigen [HBsAg]-positive or hepatitis B virus deoxyribonucleic acid [HBV DNA]-positive)
- •Has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or cutaneous Kaposi's sarcoma
- •Has a history or current evidence of any condition (including active tuberculosis infection), therapy, laboratory abnormality or other circumstance (including drug or alcohol use or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with the participant's participation for the full duration of the study
- •Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1
- •Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapy from 45 days prior to Day 1 through the study intervention period
- •Is currently participating in or has participated in a clinical study with an investigational compound or device from 45 days prior to Day 1 through the study intervention period
- •Has a documented or known virologic resistance to any approved HIV-1 reverse transcriptase inhibitor, or any study intervention
- •Has exclusionary laboratory values within 45 days prior to Day 1
- •Is female and is expecting to conceive or donate eggs at any time during the study
研究组 & 干预措施
Group 1: doravirine/islatravir (DOR/ISL)
Treatment-naïve participants living with human immunodeficiency virus-1 (HIV-1) that had not received ≤10 days of prior antiretroviral therapy received blinded fixed dose combination (FDC) Doravirine/Islatravir (DOR/ISL) (100 mg doravirine [DOR]/0.75 mg islatravir [ISL]) and placebo to Bictegravir/Tenofovir Alafenamide/Emtricitabine (BIC/FTC/TAF) once daily (QD) from Day 1 to Week 96, and open-label DOR/ISL up to Week 144. At Week 144, participants who consent to enter the optional open-label study extension continued to receive open-label QD FDC of DOR/ISL (100 mg/0.75 mg) for an additional 24 weeks, up to Week 168.
干预措施: DOR/ISL (Drug)
Group 1: doravirine/islatravir (DOR/ISL)
Treatment-naïve participants living with human immunodeficiency virus-1 (HIV-1) that had not received ≤10 days of prior antiretroviral therapy received blinded fixed dose combination (FDC) Doravirine/Islatravir (DOR/ISL) (100 mg doravirine [DOR]/0.75 mg islatravir [ISL]) and placebo to Bictegravir/Tenofovir Alafenamide/Emtricitabine (BIC/FTC/TAF) once daily (QD) from Day 1 to Week 96, and open-label DOR/ISL up to Week 144. At Week 144, participants who consent to enter the optional open-label study extension continued to receive open-label QD FDC of DOR/ISL (100 mg/0.75 mg) for an additional 24 weeks, up to Week 168.
干预措施: Placebo to BIC/FTC/TAF (Drug)
Group 2: bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF)
Treatment-naïve participants living with HIV-1 that had not received ≤10 days of prior antiretroviral therapy received blinded BIC/FTC/TAF (50 mg bictegravir [BIC], 200 mg emtricitabine [FTC], 25 mg tenofovir alafenamide [TAF]) and placebo to FDC DOR/ISL QD from Day 1 to Week 96, and open-label BIC/FTC/TAF up to Week 144. At Week 144, participants who consent to enter the optional open-label study extension continued to receive QD BIC/FTC/TAF (50 mg/200 mg/25 mg) for an additional 24 weeks, up to Week 168.
干预措施: BIC/FTC/TAF (Drug)
Group 2: bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF)
Treatment-naïve participants living with HIV-1 that had not received ≤10 days of prior antiretroviral therapy received blinded BIC/FTC/TAF (50 mg bictegravir [BIC], 200 mg emtricitabine [FTC], 25 mg tenofovir alafenamide [TAF]) and placebo to FDC DOR/ISL QD from Day 1 to Week 96, and open-label BIC/FTC/TAF up to Week 144. At Week 144, participants who consent to enter the optional open-label study extension continued to receive QD BIC/FTC/TAF (50 mg/200 mg/25 mg) for an additional 24 weeks, up to Week 168.
干预措施: Placebo to DOR/ISL (Drug)
结局指标
主要结局
Percentage of Participants With Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48
时间窗: Week 48
The Abbott RealTime polymerase chain reaction (PCR) assay with a reliable lower limit of quantification of 40 copies/mL was used to measure the HIV-1 RNA level in blood samples obtained at each visit. The percentage of participants with HIV-1 RNA \<50 copies/mL at Week 48 was presented using the Food and Drug Administration (FDA) Snapshot missing data approach. The final analysis for this outcome is presented here.
Percentage of Participants Who Experienced an Adverse Event (AE) up to Week 48
时间窗: Up to approximately 48 weeks
An AE was any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who experienced at least one AE up to Week 48 was reported. The final analysis for this outcome is presented here.
Percentage of Participants Who Discontinued Study Treatment Due to an AE up to Week 48
时间窗: Up to approximately 48 weeks
An AE was any untoward medical occurrence in a study participant administered a study drug, which does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the study drug whether or not it is considered related to the study drug. The percentage of participants who discontinued study treatment due to an AE up to Week 48 were reported. The final analysis for this outcome is presented here.
次要结局
- Percentage of 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 144(Week 144)
- Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48(Week 48)
- Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 48(Week 48)
- Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96(Week 96)
- Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 96(Week 96)
- Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 144(Week 144)
- Percentage of Participants With HIV-1 RNA <200 Copies/mL at Week 144(Week 144)
- Incidence of Viral Resistance-Associated Substitutions (RASs) at Week 48(Week 48)
- Incidence of Viral RASs at Week 96(Week 96)
- Incidence of Viral RASs at Week 144(Week 144)
- Mean Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 48(Baseline (Day 1) and Week 48)
- Mean Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 96(Baseline (Day 1) and Week 96)
- Mean Change From Baseline in Cluster of Differentiation 4+ (CD4+) T-Cell Counts at Week 144(Baseline (Day 1) and Week 144)
- Mean Change From Baseline in Body Weight at Week 48(Baseline (Day 1) and Week 48)
- Mean Change From Baseline in Body Weight at Week 96(Baseline (Day 1) and Week 96)
- Mean Change From Baseline in Body Weight at Week 144(Baseline (Day 1) and Week 144)
- Percentage of Participants Who Experienced an Adverse Event (AE)(Up to approximately 47 months)
- Percentage of Participants Who Discontinued Study Treatment Due to an AE(Up to approximately 38 months)