NCT01910402已完成3 期
A Phase IIIb, Randomized, Open-label Study of the Safety and Efficacy of Dolutegravir/Abacavir/Lamivudine Once Daily Compared to Atazanavir and Ritonavir Plus Tenofovir/Emtricitabine Once Daily in HIV-1 Infected Antiretroviral Therapy Naïve Women
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 499
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL at Week 48
研究概览
简要总结
This study is designed to demonstrate the non-inferior antiviral activity of DTG/ABC/3TC fixed dose combination (FDC) once daily (OD) compared to atazanavir plus ritonavir (ATV+RTV) and tenofovir disoproxil fumarate/emtricitabine fixed dose combination (TDF/FTC FDC) OD in HIV-1 infected, ART-naïve women over 48 weeks. This study will also characterize the safety and tolerability of DTG/ABC/3TC FDC compared to ATV+RTV+TDF/FTC FDC. Sufficient number of subjects will be screened in order to ensure a total of approximately 474 subjects will be randomized (237 in each study arm)
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •HIV-1 infected females (gender at birth) >=18 years of age
- •Women capable of becoming pregnant must use appropriate contraception during the study (as defined by the protocol)
- •HIV-1 infection as documented by Screening plasma HIV-1 RNA >=500 c/mL.
- •Documentation that the subject is negative for the HLA-B*5701 allele.
- •Antiretroviral-naïve (<=10 days of prior therapy with any antiretroviral agent following a diagnosis of HIV-1 infection).
- •Signed and dated written informed consent is obtained from the subject or the subject's legal representative prior to screening.
排除标准
- •Women who are pregnant or breastfeeding
- •Women who plan to become pregnant during the first 48 weeks of the study
- •Any subject who has had a medical intervention for gender reassignment
- •Any evidence of an active Centers for Disease Control and Prevention (CDC) Category C disease
- •Subjects with any degree of hepatic impairment
- •Subjects positive for hepatitis B at Screening, or anticipated need for HCV therapy during the study
- •History or presence of allergy to the study drugs or their components or drugs of their class
- •Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non-invasive cutaneous squamous cell carcinoma, or cervical intraepithelial neoplasia
- •poses a significant suicidality risk
- •History of osteoporosis with fracture or requiring pharmacologic therapy
- •Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening
- •Treatment with any of the following agents within 28 days of Screening: radiation therapy; cytotoxic chemotherapeutic agents; any immunomodulators that alter immune responses;
- •Treatment with any agent, with documented activity against HIV-1 in vitro within 28 days of first dose of investigational product (IP)
- •Exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of IP
- •Any evidence of primary viral resistance based on the presence of any major resistance-associated mutation in the Screening result or, if known, any historical resistance test result
- •Any verified Grade 4 laboratory abnormality, with the exception of Grade 4 lipid abnormalities (total cholesterol, triglycerides, High Density Lipoprotein (HDL) cholesterol, Low Density Lipoprotein (LDL) cholesterol)
- •Any acute laboratory abnormality at Screening, which, in the opinion of the Investigator, would preclude the subject's participation in the study of an investigational compound
- •Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN), or ALT ≥ 3xULN and bilirubin ≥ 1.5xULN (with >35% direct bilirubin)
- •Subject has CrCL of <50 mL/min via Cockroft-Gault method
- •Corrected QT interval (QTc (Bazett)) ≥450msec or QTc (Bazett) ≥480msec for subjects with bundle branch block.
研究组 & 干预措施
DTG/ABC/3TC FDC
Experimental
As per the randomization schedule subjects will be administered with DTG/ABC/3TC (50mg/600mg/300mg) FDC tablet OD up to Week 48 and if continued if applicable in the Continuation Phase. DTG/ABC/3TC FDC may be administered with or without food
干预措施: Dolutegravir/abacavir/lamivudine FDC (Drug)
ATV +RTV +TDF/FTC FDC
Active Comparator
As per the randomization schedule subjects will be administered with ATV (300mg capsule) +RTV (100mg tablet) + TDF/FTC (300mg/200mg tablet) FDC OD up to Week 48. ATV+RTV+ TDF/FTC FDC must be taken with food
干预措施: Tenofovir/emtricitabine FDC (Drug)
ATV +RTV +TDF/FTC FDC
Active Comparator
As per the randomization schedule subjects will be administered with ATV (300mg capsule) +RTV (100mg tablet) + TDF/FTC (300mg/200mg tablet) FDC OD up to Week 48. ATV+RTV+ TDF/FTC FDC must be taken with food
干预措施: Atazanavir (Drug)
ATV +RTV +TDF/FTC FDC
Active Comparator
As per the randomization schedule subjects will be administered with ATV (300mg capsule) +RTV (100mg tablet) + TDF/FTC (300mg/200mg tablet) FDC OD up to Week 48. ATV+RTV+ TDF/FTC FDC must be taken with food
干预措施: Ritonavir (Drug)
结局指标
主要结局
Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL at Week 48
时间窗: Week 48
Percentage of participants with plasma human immunodeficiency virus type 1(HIV-1) ribonucleic acid (RNA) \<50 copies per milliliter (c/mL) were assessed at Week 48 using the Snapshot algorithm. Analysis was performed using a stratified analysis with Cochran-Mantel-Haenszel (CMH) weights, adjusting for Baseline plasma HIV-1 RNA ( =\<vs. \>100,000 c/mL) and CD4+ cell count (=\<350 cells per millimeter cube (cells/mm\^3) or \>350 cells/mm\^3). Intent-to-Treat Exposed (ITT-E) Population comprised of all randomized participants who received at least one dose of study medication. Percentage values are rounded off.
次要结局
- Percentage of Participants With Plasma HIV-1 RNA <50 and <400 c/mL Over Time-Randomized Phase(Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48)
- Change From Baseline in Carbon Dioxide, Electrolytes, Lipids, Glucose, Urea at Indicated Time Points(Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48)
- Percentage of Participants With Plasma HIV-1 RNA <50 c/mL in Continuation Phase(Week 96 and Week 432)
- Change From Baseline in Plasma HIV-1 RNA at Indicated Time Points-Continuation Phase(Baseline (Day 1), Week 96 and Week 432)
- Absolute Values in Plasma HIV-1 RNA at Indicated Time Points-Randomized Phase(Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48)
- Absolute Values in CD4+ Cell Count at Indicated Timepoints-Continuation Phase(Week 96 and Week 432)
- Change From Baseline in Albumin at Indicated Timepoints(Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48)
- Absolute Values in Plasma HIV-1 RNA at Indicated Time Points-Continuation Phase(Week 96 and Week 432)
- Change From Baseline in TC/HDL Ratio at Week 48(Baseline (Day 1) and Week 48)
- Number of Participants With AEs by Maximum Toxicity-Randomized Phase(Up to Week 48)
- Number of Participants With Any AEs, and SAEs in Continuation Phase(From Weeks 48 to 432)
- Change From Baseline in Bone Specific Alkaline Phosphatase, Osteocalcin and Procollagen 1 N-terminal Propeptide at Indicated Timepoints(Baseline (Day 1), Weeks 24 and 48)
- Change From Baseline at Week 48 in SF-12 Total Score, MCS and PCS(Baseline (Day 1) and Week 48)
- Change From Baseline in Plasma HIV-1 RNA at Indicated Time Points-Randomized Phase(Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48)
- Change From Baseline in CD4+ Cell Count at Indicated Timepoints-Randomized Phase(Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48)
- Change From Baseline in Creatinine Clearance at Indicated Time Points(Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48)
- Change From Baseline in Erythrocytes at Indicated Time Points(Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48)
- Change From Baseline in CD4+ Cell Count at Indicated Timepoints-Continuation Phase(Baseline (Day 1), Week 96, Week 432)
- Absolute Values in CD4+ Cell Count at Indicated Timepoints-Randomized Phase(Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48)
- Change From Baseline in Total CHLS/HDL CHLS Ratio at Indicated Timepoints(Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48)
- Change From Baseline in Erythrocyte Mean Corpuscular Volume at Indicated Time Points(Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48)
- Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities-Randomized Phase(Up to Week 48)
- Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities-Randomized Phase(Up to Week 48)
- Change From Baseline in Bilirubin and Creatinine at Indicated Timepoints(Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48)
- Change From Baseline in Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Creatine Kinase at Indicated Time Points(Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48)
- Change From Baseline in Lipase at Indicated Timepoints(Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48)
- Number of Participants Who Withdrew From Treatment Due to AEs-Continuation Phase(From Weeks 48 to 432)
- Change From Baseline in Type I Collagen C-telopeptides at Indicated Timepoints(Baseline (Day 1), Weeks 24 and 48)
- Bone Specific Alkaline Phosphatase, Osteocalcin, Procollagen 1 N-terminal Propeptide, Type 1 Collagen C-Telopeptide, Vitamin D Ratio of Week 48 Results Over Baseline(Baseline (Day 1) and Week 48)
- Change From Baseline in Basophils, Eosinophils, Lymphocytes, Monocytes at Indicated Time Points(Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48)
- Change From Baseline in Hematocrit Count at Indicated Time Points(Baseline (Day 1), Week 4, Week 12, Week 24, Week 36 and Week 48)
- Change From Baseline in Urine Albumin Creatinine Ratio at Indicated Time Points(Baseline (Day 1), Week 24 and Week 48)
- Number of Participants With AEs by Maximum Toxicity-Continuation Phase(From Weeks 48 to 432)
- Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities-Continuation Phase(From Weeks 48 to 432)
- Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities-Continuation Phase(From Weeks 48 to 432)
- Change From Baseline in Vitamin D, Vitamin D2 and Vitamin D3 at Week 24 and Week 48(Baseline (Day 1), Weeks 24 and 48)
- Percentage of Participants With Plasma HIV-1 RNA <50 Copies/mL at Week 48 by Subgroups(Week 48)
- Number of Participants With Treatment Emergent Resistances for ATV 300 mg+RTV 100 mg+TDF 300 mg/FTC 200mg QD (Randomized Phase)(Up to week 48)
- Change From Baseline in Triglycerides at Week 48(Baseline (Day 1) and Week 48)
- Number of Participants With Any Adverse Events (AEs), and Serious Adverse Events (SAEs)-Randomized Phase(Up to Week 48)
- HIVTSQs Total Score at Indicated Timepoints(Weeks 4, 12, 24 and 48)
- Number of Participants Who Withdrew From Treatment Due to AEs-Randomized Phase(Up to Week 48)
- Number of Participants With Treatment Emergent Resistances for DTG 50 mg/ABC 600 mg/3TC 300 mg QD (Randomized + Continuation Phase)(Up to week 432)
- Number of Participants With Post-Baseline HIV-1 Disease Progression-Randomized Phase(Up to week 48)
- Number of Participants With Post-Baseline HIV-1 Disease Progression for DTG 50 mg/ABC 600 mg/3TC 300 mg QD (Randomized + Continuation Phase)(Up to week 432)
研究者
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