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Clinical Trial for Malaria Vaccines to Test for Safety, Immune Response and Protection Against Malaria (DNA-Ad)

Clinical Trial on Safety, Immunogenicity, and Efficacy of a Prime Boost Regimen of DNA- and Adenovirus-vectored Malaria Vaccines Encoding Plasmodium Falciparum Circumsporozoite Protein and Apical Membrane Antigen 1 in Healthy Malaria-Naïve Adults in the US

The purpose of this study is to test the safety and effectiveness of a new malaria vaccine, the DNA-Ad vaccine. The study is specifically looking at a vaccine regimen against Plasmodium falciparum, the most deadly form of malaria.

研究概览

详细说明

The goal of this study is to evaluate if the DNA-Ad vaccine that targets both the liver and blood stages of the malaria life cycle is safe and protective, in hopes to develop a vaccine to prevent infection and/or lessen the severity of disease caused by the P. falciparum malaria parasite. More specifically, this DNA-Ad vaccine contains a liver stage antigen (circumsporozoite protein) and an antigen (apical membrane antigen 1) that is present in both the liver and blood stages designed to prevent infection by killing the majority of developing parasites in the liver and to prevent severe disease and death should break-through blood stage infections occur.

This study is an open-label, Phase 1/2a study designed to assess the safety, immunogenicity, and efficacy of a DNA-Ad vaccine in healthy adults who are Ad5 seropositive or seronegative. The vaccinated study group will consist of up to 20 healthy, malaria-naïve adults aged 18 to 50 years, who have been previously screened to meet inclusion and exclusion criteria and will receive three priming doses of the DNA vaccine and a single dose of the boosting component, an adenovirus-vectored vaccine to be given 4 months after the last dose of DNA. Follow up visits will occur after each immunization. The control group will consist of six non-immunized subjects that will participate in a challenge to assure that vaccinated subjects were indeed exposed to P. falciparum. Subjects in both the immunized and control cohorts will receive malaria challenge. Subjects will be assessed for development of parasitemia by daily blood smears and will be closely observed in hotel after the challenge. Subjects will then be followed periodically and have the final in-person visit twelve weeks after the challenge, followed by annual contact by phone, email, or mailings up to five years after the first dose of immunization per FDA recommendation.

研究类型

介入性

注册 (实际的)

82

阶段

  • 阶段2
  • 阶段1

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

    • Maryland
      • Silver Spring、Maryland、美国、20910
        • Clinical Trials Center, WRAIR

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 adults 18 to 50 years of age (inclusive)
  • Women who are not pregnant by a current negative pregnancy test or of non-childbearing potential
  • Willing to use an FDA approved birth control method including condoms, birth control pills, sterility surgery, or intrauterine devices among others, from time of enrollment until 6 months after the end of the active phase of the study
  • Able to provide free and willing written informed consent to participate
  • Score at least 80% correct on a 10 question Assessment of Understanding
  • No plans to travel to a malaria endemic area during the course of the study
  • Free of significant health problems as established by medical history and clinical examination completed prior to the study
  • Available to participate and reachable for duration of study (up to five years)
  • Only subjects with no or low cardiac risk factors according to the Gaziano study [53] and a normal EKG will be included in the study

Exclusion Criteria:

  • Pregnant (positive HCG) or nursing at screening or plans to become pregnant or nurse from the time of enrollment until 6 months after sporozoite challenge
  • Any past history of malaria
  • History of receipt of malaria vaccine
  • Plans to travel to malarious areas during the study period
  • Use of any investigational or non-registered drug or vaccine within 30 days prior to enrollment
  • Seropositive for HIV, hepatitis C virus (antibodies to HIV and HCV), and/or HBsAg
  • Subjects in the immunized group who engage in high-risk behaviors for acquiring HIV
  • Allergy to antimalarials or significant (e.g. systemic) hypersensitivity reactions to mosquito bites (local hypersensitivity reactions at the site of a mosquito bite are not an exclusion criterion)
  • History of psoriasis (given its interaction with chloroquine)
  • Use or planned use of any drugs with significant anti-malarial activity, such as doxycycline, clindamycin, azithromycin, or trimethoprim/sulfamethoxazole among others during the study period (subjects can withhold the use of these medications during the study period if approved by their primary care physicians, at the minimum starting from four weeks before vaccine administration until four weeks after becoming parasitemic) Any confirmed or suspected immunosuppressive or immunodeficient condition, including HIV infection and history of splenectomy
  • Administration of chronic (defined as more than 14 days) immunosuppressants or other immune-modifying drugs within six months of challenge
  • A family history of congenital or hereditary immunodeficiency
  • Chronic or active neurologic disease including seizure disorder
  • Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by medical history, physical examination, or abnormal baseline laboratory screening tests.
  • Abnormal baseline EKG obtained at screening
  • Acute disease at the time of enrollment
  • Hepatomegaly, right upper quadrant abdominal pain or tenderness: noted by physical exam during the screening process.
  • Administration of immunoglobulins and/or any blood products within the three months preceding immunization during the study period
  • Use of kanamycin or related antibiotics
  • Suspected or known current alcohol abuse/drug abuse as obtained by history and physical examination
  • Inability to make follow-up visits
  • Any other significant finding that in the opinion of the investigator would increase the risk of having an adverse outcome from participating in this study.

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:非随机化
  • 介入模型:单组作业
  • 屏蔽:无(打开标签)

武器和干预

参与者组/臂
干预/治疗
实验性的:1
DNA vaccine prime Given at 0, 4, and 8 weeks
2 mg total dose (1 mg per construct in a volume of 1 mL)
实验性的:2
adenovirus type 5 vaccine boost Given at 24 weeks
2 x 1010 particle units (pu) (1 x 1010 pu per each of 2 constructs including CSP and AMA1 respectively)

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
Number of adverse events
大体时间:5 years

The vaccine will be considered safe and well-tolerated if there are no severe or serious adverse events (AE) related to vaccine administration or if any severe events are relatively benign (e.g.

erythema meeting criteria for severe due to its dimensions but not significantly affecting the activities of daily living for the subject) or brief in duration (e.g. less than 48 hours). The AEs will be assessed according to the method below.

  1. Occurrence, severity, and duration of any solicited symptoms starting on the day of immunization through day 7 after each immunization
  2. Occurrence of any unsolicited symptoms, abnormal physical findings, and laboratory values starting from the day of immunization through day 28 after each immunization
  3. Occurrence of any serious adverse events, as defined in 21 CFR 312.32, during the five-year study period
5 years

次要结果测量

结果测量
措施说明
大体时间
Number of sterile or partial protections
大体时间:28 days after malaria challenge
The DNA-Ad vaccine is considered efficacious if it offers any degree of sterile or partial protection that reaches statistical significance (p<0.05). The vaccine efficacy will be determined by two parameters: 1) sterile protection for 28 days after challenge, 2) partial protection as determined by delay to parasitemia by smears and PCR.
28 days after malaria challenge
Number of humoral immunity expressions
大体时间:28 days after malaria challenge
The DNA-Ad vaccine is considered to confer humoral immunity if the increase of antibody response for CSP or AMA1 by ELISA post immunization is statistically significant (p<0.05) compared to the levels before immunization.
28 days after malaria challenge
Number of cellular immunity expressions
大体时间:28 days after malaria challenge
The DNA-Ad vaccine is considered to confer cellular immunity if a positive ELISpot response is detected after immunization
28 days after malaria challenge

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

  • 首席研究员:Judith Epstein, MD、US Military Vaccine Program, NMRC PI, Naval Officer

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。

一般刊物

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 (实际的)

2009年5月1日

初级完成 (实际的)

2014年4月1日

研究完成 (实际的)

2015年7月1日

研究注册日期

首次提交

2009年3月27日

首先提交符合 QC 标准的

2009年3月27日

首次发布 (估计)

2009年3月30日

研究记录更新

最后更新发布 (实际的)

2021年2月11日

上次提交的符合 QC 标准的更新

2021年2月10日

最后验证

2021年2月1日

更多信息

与本研究相关的术语

关键字

其他研究编号

  • WRAIR 1550
  • HRPO #A-15350
  • NMRC.2009.0004

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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