Albuvirtide in Combination With 3BNC117 in Virologically Suppressed Subjects With HIV-1 Infection
The Phase 2, Two Arms, One Site, Safety and Antiviral Activity of Combination Therapy With Albuvirtide and 3BNC117 in Virologically Suppressed Subjects With HIV-1 Infection After Analytical Treatment Interruption
研究概览
详细说明
This is an open-label, one site study, in which a total of 24 HIV-1 subjects who are virologically suppressed and stable on daily oral combination antiretroviral therapy will be enrolled.
All eligible patients will be switched from daily oral combination antiretroviral regimen to treatment of ABT and 3BNC117 for 14 weeks. There is a two-week overlap of the baseline oral antiretroviral therapy and the ABT-3BNC117 combination regimen at the beginning of the study treatment, and then the oral ART will be interrupted.
The patients will be monitored for viral rebound every two or four weeks following initiation of ABT-3BNC117 combination and will re-initiate an oral antiretroviral regimen if virological rebound is confirmed with plasma HIV-1 RNA levels above 200 copies/ml on two consecutive test.
Pharmacokinetics of ABT and 3BNC117 will be assessed in this study.
研究类型
注册 (预期的)
阶段
- 阶段2
联系人和位置
学习地点
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Beijing、中国
- Peking Union Medical College Hospital
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Males and females, age ≥18 years
For cohort 1: HIV-1 infected subjects initiated a stable combination antiretroviral therapy (ART) within 6 months of primary HIV infection (PHI), having the document evidence of initial diagnosis of HIV-1 infection and initiation of ART therapy within 6 months of PHI.
For cohort 2: Chronically HIV-1 infected subjects initiated a stable combination antiretroviral therapy (ART) after 6 months of primary HIV infection (PHI), having the document evidence of initial diagnosis of HIV-1 infection and initiation of ART therapy after 6 months of PHI.
- Plasma HIV-1 RNA <50 copies/mL for at least 12 months prior to Screening Visit. An exception for a recorded HIV-1 RNA "blip" (e.g., transient HIV-1 RNA >50 copies/mL) can be considered.
- Plasma HIV-1 RNA <20 copies/mL at Screening Visit.
- CD4 cell count >500 cells/µL.
Laboratory values at Screening of:
- Absolute neutrophil count (ANC) ≥0.75×10∧9/L;
- Hemoglobin (Hb) ≥105 g/L (male) or ≥95 g/L (female);
- Platelets ≥75×10∧9/L;
- Serum alanine transaminase (SGPT/ALT) < 2 x upper limit of normal (ULN)
- Serum aspartate transaminase (SGOT/AST) < 2 x ULN
- Bilirubin (total) <2.5 x ULN unless Gilbert's disease is present or subject is receiving atazanavir in the absence of other evidence of significant liver disease
- Creatinine ≤1.5 x ULN
- Clinically normal resting 12-lead ECG at Screening Visit or, if abnormal, considered not clinically significant by the Principal Investigator.
- Both male and female patients and their partners of childbearing potential must agree to use accepted methods of contraception.
- Females of childbearing potential must have a negative serum pregnancy test at Screening visit and negative urine pregnancy test prior to receiving the first dose of study drug.
- Subjects who have two or more potential alternative antiretroviral treatment regimens.
- Willing and able to participate in all aspects of the study, including use of IV medication, completion of evaluations, attendance at scheduled clinic visits, and compliance with all protocol requirements as evidenced by providing written informed consent.
Exclusion Criteria:
- Any active infection or malignancy requiring acute therapy.
- Hepatitis B infection as manifest by the presence of Hepatitis B surface antigen (HBsAg).
- Hepatitis C infection as manifest by positive anti-HCV antibody and positive HCV RNA assay at the time of screening.
- Females who are pregnant, lactating, or breastfeeding, or who plan to become pregnant during the study
- Unexplained fever or clinically significant illness within 1 week prior to the first study dose
- Any vaccination within 2 weeks prior to the first study dose.
- Subjects BMI<20 or >27 kg/m∧2 [BMI=weight/height∧2].
- History of Bleeding Disorder or patients on anti-coagulant therapy
- Participation in an experimental drug trial(s) within 30 days of the Screening Visit
- Any known allergy or antibodies to the study drug or excipients
Treatment with any of the following:
- Radiation or cytotoxic chemotherapy with 30 days prior to the screening visit
- Receipt of any fusion inhibitor and monoclonal antibody therapy of any kind in the past.
- Immunosuppressants within 60 days prior to the Screening Visit
- Immunomodulating agents (e.g., interleukins, interferons), hydroxyurea, or foscarnet within 60 days prior to the screening visit
- Oral or parenteral corticosteroids within 30 days prior to the Screening Visit. Subjects on chronic steroid therapy > 5 mg/day will be excluded with the following exception:
- Subjects on inhaled, nasal, or topical steroids will not be excluded
- Any other clinical condition that, in the Investigator's judgment, would potentially compromise study compliance or the ability to evaluate safety/efficacy.
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:非随机化
- 介入模型:并行分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Early treatment of infection
HIV-1 infected subjects initiated a stable combination antiretroviral therapy (ART) within 6 months of primary HIV infection (PHI), and had plasma HIV-1 RNA <50 copies/mL for at least 12 months. Albuvirtide 0.32 g and 3BNC117 2 g every 2 weeks IV infusion for a total of 14 weeks. |
长效 HIV-1 融合抑制剂(针对 HIV-1 gp41 的化学修饰肽)
其他名称:
Recombinant, fully human mAb of the IgG1κ isotype that specifically binds to HIV-1 gp120.
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实验性的:Chronic period of infection treatment
Chronically HIV-1 infected subjects initiated a stable combination antiretroviral therapy (ART) after 6 months of primary HIV infection (PHI), and had plasma HIV-1 RNA <50 copies/mL for at least 12 months. Albuvirtide 0.32 g and 3BNC117 2 g every 2 weeks IV infusion for a total of 14 weeks. |
长效 HIV-1 融合抑制剂(针对 HIV-1 gp41 的化学修饰肽)
其他名称:
Recombinant, fully human mAb of the IgG1κ isotype that specifically binds to HIV-1 gp120.
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Proportion of participants (with sustained viral suppression at week 14) with HIV-1 RNA < 50 copies/mL at Week 26 (24 weeks after ATI)
大体时间:Week 26
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Proportion of participants with HIV-1 RNA < 50 copies/mL at Week 26.
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Week 26
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Mean time to virologic rebound (HIV-1 RNA≥200 copies/mL) after ATI
大体时间:up to 48 weeks
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Mean time to virologic rebound
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up to 48 weeks
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Proportion of participants without experiencing virologic rebound (HIV-1 RNA<200 copies/mL) at Week 26 (24 weeks after ATI).
大体时间:Week 26
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Proportion of participants without experiencing virologic rebound
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Week 26
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Proportion of participants with HIV-1 RNA < 50 copies/mL at Week 26 (24 weeks after ATI).
大体时间:Week 26
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Proportion of participants with HIV-1 RNA < 50 copies/mL at Week 26
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Week 26
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Mean change in CD4 cell count after ATI
大体时间:up to 48 weeks
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Mean change in CD4 cell count
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up to 48 weeks
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Mean change in CD4/CD8 ration after ATI
大体时间:up to 48weeks
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Mean change in CD4/CD8 ration
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up to 48weeks
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Frequency of emergence of new resistance mutations after virologic rebound
大体时间:up to 48 weeks
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Frequency of emergence of new resistance mutations
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up to 48 weeks
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Mean time to achieving HIV-1 RNA < 50 copies/mL after experiencing virologic rebound
大体时间:up to 48 weeks
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Mean time to achieving HIV-1 RNA < 50 copies/mL after experiencing virologic rebound
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up to 48 weeks
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合作者和调查者
调查人员
- 研究主任:Cheng Yao、Frontier Biotechnologies Inc.
研究记录日期
研究主要日期
学习开始 (预期的)
初级完成 (预期的)
研究完成 (预期的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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