NCT03041012已完成2 期
Early Administration of Latency Reversing Therapy and Broadly Neutralizing Antibodies to Limit the Establishment of the HIV-1 Reservoir During Initiation of Antiretroviral Treatment - a Randomized Controlled Trial
Aarhus University Hospital4 个研究点 分布在 2 个国家目标入组 60 人开始时间: 2017年1月20日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 60
- 试验地点
- 4
- 主要终点
- Quantification of the size of the proviral HIV reservoir
研究概览
简要总结
To evaluate the effect of early viral reactivation by latency reversing agents (LRA) and/or administration of potent broadly neutralizing antibodies (bNAb) on the size of the latent HIV-1 reservoir in treatment naïve HIV-1 patients initiating antiretroviral therapy (ART)
详细描述
The study will be conducted among ART naïve HIV-1-infected patients.
Subjects will continue ART while receiving LRA romidepsin and/or bNAb 3BNC117.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 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
- •Documented HIV-1 infection
- •CD4+ T cell count >200/µL on last visit prior to study entry
- •ART naïve
- •Able to give informed consent
排除标准
- •Any significant acute medical illness (not including primary HIV infection) in the past 8 weeks
- •Any evidence of an active AIDS-defining opportunistic infection
- •Active alcohol or substance use that, in the Investigator's opinion, will prevent adequate compliance with study therapy
- •The following laboratory values at screening, but the values can be repeated within the screening period, but test results must be available before baseline (day 0) and checked for eligibility:
- •Hepatic transaminases (AST or ALT) ≥3 x upper limit of normal (ULN)
- •Serum total bilirubin ≥3 ULN
- •Estimated glomerular filtration rate (eGFR) ≤60 mL/min (based on serum creatinine or other appropriate validated markers)
- •Platelet count ≤100 x10^9/L
- •Absolute neutrophil count ≤1x10^9/L
- •Serum potassium, magnesium, phosphorus outside ≥1.5 ULN/LLN
- •Total calcium (corrected for serum albumin) or ionized calcium ≥1.5 ULN/LLN
- •Hepatitis B or C infection as indicated by the presence of hepatitis B surface antigen (HBsAg) or hepatitis C virus RNA (HCV-RNA) in blood
- •ECG at screening that shows QTc >450 ms when calculated using the Fridericia formula from either lead V3 or V4 [86]
- •Warfarin or warfarin-derivatives
- •An agent definitely or possibly associated with effects on QT intervals within 2 weeks of screening
- •Drugs that induce or inhibit CYP3A4 or P-gp
- •History of:
- •Clinically significant cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for Torsades de pointes (e.g. heart failure)
- •Malignancy or transplantation, including skin cancers or Kaposi sarcoma
- •Diabetes mellitus
- •Receipt of strong immunosuppressive or systemic chemotherapeutic agents within 28 days prior to study entry
- •Known resistance to >2 classes of ART
- •Known hypersensitivity to the components of romidepsin, 3BNC117 or their analogues
- •Women who are pregnant or breastfeeding, or with a positive pregnancy test during screening or Women of Child Bearing Potential (WOCBP) who are unwilling or unable to use an acceptable method of non-estrogen containing contraceptions (according to the Danish Medicines Agency guidelines) to avoid pregnancy for the 3 week study period and 4 weeks after study treatment or until undetectable plasma HIV-1 RNA using standard assays
- •Males or females who are unwilling or unable to use barrier contraception during sexual intercourse for the 3-week study period, and 4 weeks after study treatment or until undetectable plasma HIV-1 RNA using standard assays
研究组 & 干预措施
antiretrovirals + romidepsin
Active Comparator
Standard of care + LRA
干预措施: Antiretrovirals (Drug)
antiretrovirals
Placebo Comparator
Standard of care
干预措施: Antiretrovirals (Drug)
antiretrovirals + romidepsin
Active Comparator
Standard of care + LRA
干预措施: Romidepsin (Drug)
antiretrovirals + 3BNC117
Active Comparator
Standard of care + bNAb
干预措施: 3BNC117 (Drug)
antiretrovirals + 3BNC117
Active Comparator
Standard of care + bNAb
干预措施: Antiretrovirals (Drug)
antiretrovirals + romidepsin + 3BNC117
Active Comparator
Standard of care + LRA + bNAb
干预措施: Romidepsin (Drug)
antiretrovirals + romidepsin + 3BNC117
Active Comparator
Standard of care + LRA + bNAb
干预措施: 3BNC117 (Drug)
antiretrovirals + romidepsin + 3BNC117
Active Comparator
Standard of care + LRA + bNAb
干预措施: Antiretrovirals (Drug)
结局指标
主要结局
Quantification of the size of the proviral HIV reservoir
时间窗: 1 year
Copies of total HIV-1 DNA per 10⁶ CD4+ T cells as measured by digital droplet PCR
Plasma HIV RNA kinetics
时间窗: 3 months
Time to undetectable (\<20 c/mL)
Time to viral rebound during ATI
时间窗: 12 weeks
Days from stopping ART to plasma HIV RNA \>5,000 on two consecutive measurements
次要结局
- Analytic treatment interruption (ATI) study(64 weeks)
- Impact of pre-ART virus sensitivity to 3BNC117 on ATI outcomes(Baseline and at viral rebound)
- Quantification of the intact proviral DNA(1 year)
- Incidence of treatment emerging events (Safety and tolerability)(1 year)
- Quantification of HIV mRNA and/or p24 positive cells(30 days from study entry)
- Immune reconstitution(1 year)
- T cell mediated HIV specific immunity(First of 365 days)
研究者
研究点 (4)
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