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Safety and Immunogenicity Study of tgAAC09, an HIV Vaccine in an Adeno-associated Virus (AAV) Capsid (TGC14F)

2012年12月13日 更新者:International AIDS Vaccine Initiative

Phase II, Placebo-controlled, Double-blind, Dose-escalation/Dose-optimization Trial to Evaluate Safety and Immunogenicity of tgAAC09, an HIV Vaccine Containing Clade C Gag-PR-ΔRT DNA in an Adeno-associated Virus (AAV) Capsid

This phase 2 study will evaluate the safety, immunogenicity and optimal timing of two injections at three dose levels of the tgAAC09 vaccine in healthy volunteers. Study volunteers will receive two intramuscular injections of tgAAC09 or placebo at Months 0 and 6 (groups A, C, E and G) or at Months 0 and 12 (groups B, D and F) and be followed for a total of 18 months following the first injection with the exception of group G in which volunteers will be followed for 12 months after the first injection (6 months after the second injection). This study will explore whether boosting is possible, and compare a shorter and more practical six-month time interval with a twelve-month time interval.

研究概览

详细说明

The study design will also assess the effect of the presence of anti-AAV2 capsid neutralizing antibodies at the time of vaccination on the safety and immunogenicity of tgAAC09. Since the prevalence of pre-existing neutralizing antibodies to AAV2 capsid is high (IAVI and Targeted Genetics, data on file), this protocol amendment adds Group G which is composed of volunteers who have documented pre-existing anti-AAV2 capsid neutralizing antibodies titers ≤ 1/8. This will assure that there are sufficient numbers of volunteers with and without antibodies for a useful comparison.

研究类型

介入性

注册 (实际的)

91

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。

学习地点

      • Entebbe、乌干达
        • Uganda Virus Research Institute
      • Cape Town、南非、7920
        • Desmond Tutu HIV Centre Cape Town
      • South Africa、南非、0204
        • Medunsa
      • Soweto、南非、2013
        • Perinatal HIV Research Unit, Baragwanath Hospital
      • Lusaka、赞比亚
        • Zambia-Emory HIV Research Project (ZEHRP)

参与标准

研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 至 50年 (成人)

接受健康志愿者

是的

有资格学习的性别

全部

描述

Inclusion Criteria:

  • Healthy male or female
  • Age at least 18 years on the day of screening and no greater than 50 years on the day of the first study injection
  • Willing to comply with the requirements of the protocol and available for follow up for the planned duration of the study
  • Able and willing to give informed consent.
  • Willing to undergo HIV testing, counseling and receive results
  • If sexually active female of child-bearing potential (not menopausal or anatomically sterile), willing to use an effective method of contraception (hormonal contraceptives; intrauterine contraceptive device (IUCD); condoms; anatomical sterility in self or partner) from screening until at least four months after last study injection and willing to undergo urine pregnancy tests at screening, prior to each injection and four months after the last injection
  • If sexually active male, willing to use a method of contraception (such as condoms) from screening until four months after the last study injection

Exclusion Criteria:

  • HIV-1 or HIV-2 infection
  • Active tuberculosis
  • Clinically relevant abnormality on history or examination including history of immunodeficiency, or cancer, or autoimmune disorder
  • Use of systemic corticosteroids, immunosuppressive or anticancer medications in the last six months
  • Chronic condition that, in the opinion of the investigator or the designated trial physician, would make the volunteer unsuitable for the study
  • Any of the following abnormal laboratory parameters:

    • Hemoglobin <9.0 g/dL (females), <12.0 g/dL (males)
    • Absolute Neutrophil Count (ANC): ≤ 999/mm3
    • Absolute Lymphocyte Count (ALC): ≤ 500/mm3
    • Platelets: decreased ≤ 90,000 or increased ≥ 550,000/mm3
    • Creatinine: > 1.4 x ULN
    • AST: >3.0 x ULN
    • ALT: >3.0 x ULN
    • Urine dipstick: blood = 2+ or more (except in menstruating females); protein = 2+ or more
  • Any of the following high-risk behaviors:

    • Had unprotected vaginal or anal sex with a known HIV positive person in the past six months
    • Had unprotected vaginal or anal sex with a casual partner (i.e. no continuing established relationship) in the past six months
    • Engaged in sex work for money or drugs in the past six months
    • Used injection drugs illegally in the past six months
    • Acquired a sexually transmitted infection (STI) in the past six months
  • If female, pregnant, lactating or planning a pregnancy within four months after last study injection
  • Receipt of live attenuated vaccine within 30 days or other vaccine within 14 days of the first study injection
  • Receipt of blood transfusion or blood products six months prior to the first study injection
  • Participation in another clinical trial of an investigational product currently or within last 12 weeks of first study injection or expected participation during this study
  • Prior receipt of an investigational HIV vaccine
  • History of severe local or systemic reaction to vaccination(s) or history of severe allergic reactions
  • History of major neurological or psychiatric disorders
  • Positive for hepatitis B surface antigen, active untreated syphilis (confirmed by treponemal test such as TPHA in addition to nontreponemal test such as RPR) or other active sexually transmitted diseases

学习计划

本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。

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:四人间

武器和干预

参与者组/臂
干预/治疗
实验性的:Group A

Number of Vaccine Recipients: 10

Dosage level 3 x 10^10 DRP

Month 0 + 6

实验性的:Group B

Number of Vaccine Recipients: 10

Dosage level 3 x 10^10 DRP

Month 0+12

实验性的:Group C

Number of Vaccine Recipients: 10

Dosage level 3 x 10^11 DRP

Month 0+6

实验性的:Group D

Number of Vaccine Recipients: 10

Dosage level 3 x 10^11 DRP

Month 0+12

实验性的:Group E

Number of Vaccine Recipients: 10

Dosage level 3 x 10^12 DRP

Month 0+6

实验性的:Group F

Number of Vaccine Recipients: 10

Dosage level 3 x 10^12 DRP

Month 0+12

实验性的:Group G

Number of Vaccine Recipients: 10

Preselected for baseline AAV neutralization titers of <1/8

Dosage level 3 x 10^12 DRP

Month 0+6

安慰剂比较:Placebo
3 volunteers will receive placebo matched to each experimental group.
Sterile isotonic buffered salt solution

研究衡量的是什么?

主要结果指标

结果测量
大体时间
Safety: proportion of volunteers with severe local and systemic reactions, proportion of volunteers with other SAEs (including laboratory abnormalities) related to study vaccine, number of volunteers with SAEs related to study vaccine
大体时间:18 months
18 months
Proportion of volunteers with HIV-1 specific T- cell responses quantified by γ-IFN ELISPOT and magnitude of the response, and proportion of volunteers with HIV-1 specific binding antibodies and magnitude of the response
大体时间:18 months
18 months

次要结果测量

结果测量
大体时间
Safety: high versus low or negative titres of neutralizing antibodies to AAV2 at the time of each vaccination
大体时间:18 months
18 months
Immunogenicity: proportion of volunteers with HIV-1 specific T- cell responses by γ-IFN CFC or other T-cell assays
大体时间:18 months
18 months
Immunogenicity endpoints in volunteers with high versus low or negative titres of neutralizing antibodies to AAV2 at the time of each vaccination
大体时间:18 months
18 months
Immunogenicity endpoints in volunteers with versus without four-fold or greater increase in titres of neutralizing antibodies to AAV2 after vaccination
大体时间:18 months
18 months
Immunogenicity endpoints after the second study injection, compared with the first study injection
大体时间:18 months
18 months
Immunogenicity endpoints after the second study injection following a twelve-month interval compared to a six-month interval
大体时间:18 months
18 months
Vaccine biodistribution: presence and persistence of vaccine in peripheral blood mononuclear cells (PBMC), saliva, nasal swabs, urine and semen or cervical/vaginal secretions
大体时间:18 months
18 months

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

调查人员

  • 学习椅:Eftyhia Vardas, MD、Perinatal HIV Research Unit (PHRU), Baragwanath
  • 首席研究员:Linda-Gail Bekker, MD、Desmond Tutu HIV Centre Cape Town
  • 首席研究员:Anwar Hoosen、Medical University of Southern Africa (Medunsa)
  • 首席研究员:Elwyn Chomba, MD、Zambia-Emory HIV Research Project (ZEHRP), Lusaka
  • 首席研究员:Pontiano Kaleebu, MD, PhD、MRC/UVRI and LSHTM Uganda Research Unit

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

有用的网址

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始

2005年10月1日

初级完成 (实际的)

2007年12月1日

研究完成 (实际的)

2007年12月1日

研究注册日期

首次提交

2009年4月23日

首先提交符合 QC 标准的

2009年4月24日

首次发布 (估计)

2009年4月27日

研究记录更新

最后更新发布 (估计)

2012年12月17日

上次提交的符合 QC 标准的更新

2012年12月13日

最后验证

2012年12月1日

更多信息

此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.

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