3BNC117 and 10-1074 in HIV Uninfected Adults
A Phase 1 Study of the Safety and Pharmacokinetics of the Combination of 3BNC117 and 10-1074 in HIV-uninfected Adults
研究概览
详细说明
The study will be conducted under a placebo-controlled, double blind, randomized allocation of the study products. Study participants in each study group will be randomized to receive intravenous infusions of 3BNC117 and 10-1074 or placebo. 3BNC117 and 10-1074 will be administered at 2 dose levels (3 mg/kg and 10 mg/kg). These doses were selected based on the planned development of subcutaneous formulations for the prophylactic use of these products. The study will consist of 3 groups. Enrollment in Group 1 will begin first and participants will be enrolled at least one day apart. Eight participants will be enrolled in each group; 6 will be randomized receive the study drugs and 2 will be randomized to receive placebo. Participants in Group 1 will receive a single infusion of each antibody at 10mg/kg at Week 0. Enrollment in Group 2 will begin only after Day 28 safety data from all participants in Group 1, including ophthalmologic exams, are available. Enrollment in Group 3 will begin only after the Day 28 safety data from all participants in Group 2 is available. If > 1 grade 3 or higher adverse events deemed probably or definitely related to the study drugs occurs in a single group, the next group will not be enrolled pending safety monitoring committee (SMC) review. Participants in Groups 2 and 3 will receive 3 infusions of each antibody at Weeks 0, 8, and 16, at a dose of either 3mg/kg or 10mg/kg. The antibodies will be administered sequentially via intravenous infusion. Each antibody will be administered over 60 minutes.
Following product infusions, study participants will return for safety assessments at multiple time points. Blood samples will be collected for safety testing at weeks 1, 2, and 4 following each infusion, then at multiple time points until the end of study follow up.
Baseline pharmacokinetic (PK) assessments will be performed before the start of the first infusion. Peak PK sampling for 3BNC117 will occur following the completion of the 3BNC117 infusion prior to the start of the 10-1074 infusion. Peak PK sampling for 10-1074 will occur following the completion of the 10-1074 infusion. Additional PK assessments will occur at multiple time points during study follow up. Study participants will be followed for a total of 24 weeks following the final antibody infusion.
研究类型
注册 (实际的)
阶段
- 阶段1
联系人和位置
学习地点
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New York
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New York、New York、美国、10065
- The Rockefeller University
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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 to 65.
- Amenable to HIV risk reduction counseling and agrees to maintain behavior consistent with low risk of HIV exposure.
- If sexually active male or female, and participating in sexual activity that could lead to pregnancy, agrees to use two effective methods of contraception (i.e. condom with spermicide, diaphragm with spermicide, hormone-eluting IUD, hormone-based contraceptive with condom) for the duration of the study.
Exclusion Criteria:
- Confirmed HIV-1 or HIV-2 infection.
- History of immunodeficiency or autoimmune disease; use of systemic corticosteroids, immunosuppressive anti-cancer, or other medications considered significant by the trial physician within the last 6 months.
- Any clinically significant acute or chronic medical condition (such as autoimmune diseases) that in the opinion of the investigator would preclude participation.
- Within the 12 months prior to enrollment, the participant has a history of sexually transmitted infection.
- Chronic Hepatitis B or Hepatitis C infection.
- Laboratory abnormalities in the parameters listed:
- Absolute neutrophil count ≤ 2,000;
- Hemoglobin ≤ 12 gm/dL if female; ≤ 13.5 gm/dL if male;
- Platelet count ≤ 125,000;
- Alanine Aminotransferase (ALT) ≥ 1.25 x ULN; Aspartate Aminotransferase (AST) ≥ 1.25 x ULN;
- Alkaline phosphatase ≥ 1.5 x ULN
- Total bilirubin > 1.0 x ULN;
- Creatinine ≥1.1 x ULN;
- Pregnancy or lactation.
- Any vaccination within 14 days prior to infusion
- Receipt of any experimental HIV vaccine in the past.
- History of severe reaction to a vaccine or drug infusion or history of severe allergic reactions.
- Participation in another clinical study of an investigational product currently or within past 12 weeks, or expected participation during this study.
学习计划
研究是如何设计的？
设计细节
- 主要用途：预防
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：三倍
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：Group 1
Participants will be randomized in a 3:1 ratio to receive one intravenous infusion of 3BNC117 and one intravenous infusion of 10-1074, each dosed at 10 mg/kg OR placebo (sterile saline), on day 0.
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3BNC117静脉滴注
其他名称：
Intravenous Infusion of 10-1074
其他名称：
Intravenous Infusion of Sterile Saline (NaCl 0.9%)
其他名称：
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实验性的：Group 2
Participants will be randomized in a 3:1 ratio to receive three intravenous infusions of 3BNC117 and three intravenous infusions of 10-1074, each dosed at 3 mg/kg OR placebo (sterile saline), on day 0, week 8, and week 16.
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3BNC117静脉滴注
其他名称：
Intravenous Infusion of 10-1074
其他名称：
Intravenous Infusion of Sterile Saline (NaCl 0.9%)
其他名称：
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实验性的：Group 3
Participants will be randomized in a 3:1 ratio to receive three intravenous infusions of 3BNC117 and three intravenous infusions of 10-1074, each dosed at 10 mg/kg OR placebo (sterile saline), on day 0, week 8, and week 16.
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3BNC117静脉滴注
其他名称：
Intravenous Infusion of 10-1074
其他名称：
Intravenous Infusion of Sterile Saline (NaCl 0.9%)
其他名称：
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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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The number of participants who experience adverse events within 1 week after the combination of 3BNC117 and 10-1074 infusion in all study groups.
大体时间：1 week following each combination of 3BNC117 and 10-1074 infusion
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Adverse events include signs, symptoms and laboratory abnormalities, in addition to local and systemic reactogenicity adverse events.
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1 week following each combination of 3BNC117 and 10-1074 infusion
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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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Number of participants with induced anti-3BNC117 and anti-10-1074 antibodies
大体时间：8 weeks following each combination of 3BNC117 and 10-1074 infusion
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8 weeks following each combination of 3BNC117 and 10-1074 infusion
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Level of induced anti-3BNC117 and anti-10-1074 antibodies
大体时间：8 weeks following each combination of 3BNC117 and 10-1074 infusion
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8 weeks following each combination of 3BNC117 and 10-1074 infusion
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The number of participants who experience adverse events that occur during study follow up after 3BNC117 and 10-1074 infusions in all study groups.
大体时间：24-40 weeks
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Adverse events include signs, symptoms and laboratory abnormalities.
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24-40 weeks
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其他结果措施
结果测量 |
大体时间 |
|---|---|
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Neutralization activity of serum from study participants against a panel of viruses as measured by the TZM.bl neutralization assay.
大体时间：24-40 weeks
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24-40 weeks
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Elimination half-life (t1/2) of 3BNC117 and 10-1074
大体时间：24-40 weeks
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24-40 weeks
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Clearance (CL/F) of 3BNC117 and 10-1074
大体时间：24-40 weeks
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24-40 weeks
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Volume of distribution (Vz/F) of 3BNC117 and 10-1074
大体时间：24-40 weeks
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24-40 weeks
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Area under the plasma concentration versus time curve (AUC) of 3BNC117 and 10-1074
大体时间：24-40 weeks
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24-40 weeks
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Decay Curve of of 3BNC117 and 10-1074
大体时间：24-40 weeks
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24-40 weeks
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合作者和调查者
调查人员
- 首席研究员：Yehuda Cohen, MD、Rockefeller University
出版物和有用的链接
一般刊物
- Valente PK, Wu Y, Cohen YZ, Caskey M, Meyers K. Behavioral and social science research to support development of educational materials for clinical trials of broadly neutralizing antibodies for HIV treatment and prevention. Clin Trials. 2021 Feb;18(1):17-27. doi: 10.1177/1740774520948042. Epub 2020 Aug 24.
- Cohen YZ, Butler AL, Millard K, Witmer-Pack M, Levin R, Unson-O'Brien C, Patel R, Shimeliovich I, Lorenzi JCC, Horowitz J, Walsh SR, Lin S, Weiner JA, Tse A, Sato A, Bennett C, Mayer B, Seaton KE, Yates NL, Baden LR, deCamp AC, Ackerman ME, Seaman MS, Tomaras GD, Nussenzweig MC, Caskey M. Safety, pharmacokinetics, and immunogenicity of the combination of the broadly neutralizing anti-HIV-1 antibodies 3BNC117 and 10-1074 in healthy adults: A randomized, phase 1 study. PLoS One. 2019 Aug 8;14(8):e0219142. doi: 10.1371/journal.pone.0219142. eCollection 2019.
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
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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3BNC117的临床试验
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Rockefeller UniversityBrigham and Women's Hospital; Weill Medical College of Cornell University; University of Cologne完全的
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International AIDS Vaccine InitiativeBrigham and Women's Hospital; Fred Hutchinson Cancer Center; Rockefeller University主动，不招人
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AIDS Clinical Trials GroupNational Institute of Allergy and Infectious Diseases (NIAID)尚未招聘
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AIDS Clinical Trials GroupNational Institute of Allergy and Infectious Diseases (NIAID)尚未招聘HIV-1-感染
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Rockefeller UniversityNational Institute of Allergy and Infectious Diseases (NIAID); Montefiore Medical Center; Weill... 和其他合作者完全的
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National Institute of Allergy and Infectious Diseases...Rockefeller University撤销