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在健康未患过疟疾的成年人中诱发血期疟疾的第一阶段研究,旨在评估间日疟原虫攻击剂的安全性和传染性,并评估蚊子喂养试验中的传播情况

Background:

Malaria is a disease caused by parasites transmitted to people by mosquitoes. Around the world, there were 241 million cases and 627,000 deaths from malaria in 2020. Researchers are working to develop vaccines and treatments for this disease.

Objective:

To learn how malaria develops in people; how the body's immune system reacts to malaria; and how malaria spreads from people to mosquitoes.

Eligibility:

Healthy people in the Washington DC area, aged 18 to 54 years. They cannot live alone during parts of the study.

Design:

Participants will be infected with a parasite that causes malaria. The parasite will be in donated blood; it will be given through an IV.

Participants will likely develop symptoms within a week after the injection. Researchers will call daily to check on their health. After about 6 days, participants will come to the NIH clinic each day for blood tests.

Participants will check in to the NIH clinic around 10 days after the injection. They will stay in the clinic 3 to 6 days. They will have multiple blood tests every day.

Participants will be bitten by mosquitoes up to 4 times. Cups containing mosquitoes will be held against their skin for 15 minutes.

Participants will begin taking chloroquine close to the end of their clinic stay. Chloroquine is a pill taken by mouth once or twice a day for 3 days. It is FDA-approved to treat malaria.

Participants will have follow-up visits 1 and 3 weeks after discharge.

研究概览

详细说明

Study Description: Single-center, open-label, phase 1 study to characterize the safety and infectivity of Plasmodium vivax (P. vivax) challenge agent for induced blood-stage malaria (IBSM) in malaria-naive participants at the NIH Clinical Center (NIHCC). Challenge agent derived from a cell bank of cryopreserved blood-stage P. vivax (PvHMB-CCE001) will be administered intravenously. A minimum of 2 participants will undergo IBSM to establish initial safety and infectivity of the challenge agent (pilot group). Additional participants, totaling 10 to 50 (main group), will be enrolled to further develop the model including to evaluate growth kinetics, transmission to mosquitoes using feeding assays and assess the host response to P. vivax infection. All participants who receive challenge agent will undergo antimalarial treatment. Qualification and characterization of the IBSM model, including transmission assays in malaria na(SqrRoot) ve,

unvaccinated participants, is a requisite goal in supporting future studies to evaluate stage-specific vaccines (transmission blocking

vaccines (TBVs) and blood stage vaccines (BSVs)) using the model.

Challenge agent derived from bank PvHMB-CCE001 will be assessed first in a pilot group of at least 2 participants, then subsequently in a main group with participants receiving inoculations in cohorts of up to 10 individuals based on logistical considerations including the capacity of clinic resources. The dose of the challenge agent may be adjusted if needed to generate reliable IBSM.

Objectives:

  • Primary Objective

    --To assess the safety of the P. vivax IBSM model following inoculation of healthy participants.

  • Secondary Objectives

    • To establish an appropriate challenge agent dose for use in P. vivax IBSM studies.
    • To evaluate transmission of P. vivax to vector mosquitoes in the IBSM model by mosquito feeding assays.
    • To establish a dataset that may be used as a historical control in future interventional IBSM transmission studies.
  • Exploratory Objectives

    • To further characterize blood and sexual stage parasite growth profiles following blood-stage P. vivax challenge and treatment.
    • To assess host responses to P. vivax IBSM.
    • To optimize mosquito infectivity in feeding assays, and study human to mosquito transmission and generate mosquito stages of the parasite.
    • To establish a supply of P. vivax infected blood.

Endpoints:

  • Primary Endpoint

    --Incidence and severity of local and systemic adverse events (AEs) or serious adverse events (SAEs).

  • Secondary Endpoints

    • A suitable dose of challenge agent that generates parasitemia in a reliable and timely manner as determined by the investigator.
    • Transmission of P. vivax to Anopheles spp. using mosquito feeding assays including direct feeding assays and/or membrane feeding assays as determined by the detection of oocysts following midgut dissection. Additional optional measures may include salivary gland dissection or detection by molecular methods.
    • Demonstration of transmission in mosquito feeding assays among a requisite number of participants.
  • Exploratory Endpoints

    • Asexual blood-stage and sexual stage parasite growth profiles by quantitative polymerase chain reaction (qPCR) and/or microscopy.
    • Antibody responses: Antibody levels elicited following IBSM as measured by enzyme-linked immunosorbent assay (ELISA) (e.g., antibodies against Pvs230, Pvs25, Pvs44/45 sexual stage antigens, or PvMSP3, MSP9, and AMA1 asexual stage antigens), cellular responses, biomarkers, and transcriptional profiling at various timepoints.
    • Collection of gametocyte-containing blood and study in mosquito transmission assays.
    • Collection of P. vivax-containing blood from participants.

研究类型

介入性

注册 (估计的)

300

阶段

  • 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。

学习联系方式

学习地点

    • Maryland
      • Bethesda、Maryland、美国、20892
        • 招聘中
        • National Institutes of Health Clinical Center
        • 接触:
          • NIH Clinical Center Office of Patient Recruitment (OPR)
          • 电话号码:TTY dial 711 800-411-1222
          • 邮箱:ccopr@nih.gov

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 54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:

All of the following criteria must be fulfilled for a participant to undergo IBSM:

  1. Age >=18 and <=54 years.
  2. RBCs positive for Duffy antigen/chemokine receptor.
  3. Malaria comprehension exam passed prior to study activities.
  4. Suitable accommodation and reliable access to the NIHCC for the duration of the study in the opinion of the investigator.
  5. Persons of childbearing potential must be willing to use reliable contraception from 28 days prior to challenge agent administration to the end of study.
  6. Signing of the informed consent form.
  7. Agreement to not live alone from challenge agent administration until the completion of antimalarial treatment.
  8. Agreement to long-term storage of study samples for future research.

EXCLUSION CRITERIA:

A participant will be excluded from participating in this trial if any 1 of the following criteria is fulfilled:

  1. Planned travel to a P. vivax-endemic area during the study period (see https://www.cdc.gov/malaria/travelers/country_table/a.html).

  2. History of travel to or residence in a P. vivax malaria-endemic region for more than 2 weeks during the past 2 years.

  3. Prior confirmed P. vivax malaria diagnosis or clinical history consistent with likely P. vivax infection. At the investigator's discretion, participants may be enrolled if the exposure was remote, e.g., > 5 years ago.

  4. Poor peripheral venous access, at the discretion of the investigator.

  5. For persons of childbearing potential:

    1. Currently pregnant or breastfeeding, or planning on becoming pregnant or breastfeeding until the end of study.
    2. Rh blood group negative.
  6. Being a current or former study team member or clinical trial staff with direct involvement of the trial, or being an employee supervised by a study team member.

  7. Unwillingness to defer blood donations for at least 3 years.

  8. Use of any of the following within the specified periods:

    1. Investigational P. vivax vaccine within the last 2 years.
    2. Malaria chemoprophylaxis within 3 months of Day 0.
    3. Chronic systemic immunosuppressive medications (>14 days) within 6 months (e.g., cytotoxic medications, adrenocorticotrophic hormone, or oral/parental corticosteroids equivalent to >0.5 mg/kg/day of prednisone). Corticosteroid nasal spray for allergic rhinitis and topical corticosteroids for mild, uncomplicated dermatitis are allowed.
    4. Prior receipt of packed red cells or other blood products or immunoglobulins within the previous 6 months.
    5. Systemic antibiotics or medications with potential antimalarial effects less than 28 days before Day 0 (e.g., clindamycin, chloroquine, benzodiazepines, tetracycline, azithromycin, or doxycycline).
    6. Investigational product or vaccine less than 28 days before Day 0.
    7. Receipt of any vaccination less than 28 days before Day 0.
    8. Current or planned use of medications known to significantly prolong the QT interval or otherwise interfere with study agents.
    9. Smoking more than 5 cigarettes or equivalent per day and unable to stop smoking for the duration of admission. Participants may smoke up to 5 cigarettes or equivalent per day for the rest of the study (by attestation).
    10. History of alcohol use disorder (exceptions may be made at the investigator's discretion if they have completed treatment or are otherwise currently abstinent) or refusal to agree to refrain from drinking from the day of the challenge agent inoculation until completion of their antimalarial course.
  9. Clinically significant medical condition, physical examination findings, other clinically significant abnormal laboratory results, or past medical history including:

    1. Immunodeficiency including asplenia or functional asplenia or significant autoimmune disease.
    2. Retinal disease, visual field changes, psoriasis, porphyria, or known allergy to chloroquine or artemether/lumefantrine.
    3. Cardiac disease including >10% cardiovascular risk as determined by the non-laboratory method or an abnormal EKG demonstrating a corrected QT interval by Fridericia's formula of >450 msec or other concerning arrhythmia.
    4. Any other medical condition that may have significant implications for current health status and participation in the study, in the opinion of the investigator.
  10. History of a severe reaction to arthropod bites, or history of anaphylaxis or severe unexpected allergy to any substance.

  11. Screening blood test or urinalysis laboratory parameters outside of local lab normal range (including infectious serologies). Participants may be included at the investigator's discretion for "not clinically significant" values outside of normal range.

  12. Any other finding that, in the judgment of the investigator, would interfere with, or serve as a contraindication to, protocol adherence, assessment of safety or reactogenicity, or a participant's ability to give informed consent, or increase the risk of having an adverse outcome from participating in the study.

Participants who are determined ineligible to participate for any of the reasons above may be rescreened for eligibility at a later time when the disqualifying condition may be resolved.

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:基础科学
  • 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:P. vivax challenge agent derived from PvHMB-CCE001 Main Arm

Up to 50 participants will undergo IBSM to further establish safety of the P. vivax challenge agent derived from PvHMB-CCE001 and evaluate transmission to mosquitoes using feeding assays and assess the host response to P. vivax infection.

P. vivax challenge agent derived from PvHMB-CCE001 consists of infected and uninfected erythrocytes stabilized in glycerolyte. Challenge agent derived from this bank consists of thawed, washed, infected and uninfected erythrocytes suspended in injectable-grade normal saline.

实验性的:P. vivax challenge agent derived from PvHMB-CCE001 Pilot Arm

2 participants will undergo IBSM to establish the safety and infectivity of the P. vivax challenge agent derived from PvHMB-CCE001.

P. vivax challenge agent derived from PvHMB-CCE001 consists of infected and uninfected erythrocytes stabilized in glycerolyte. Challenge agent derived from this bank consists of thawed, washed, infected and uninfected erythrocytes suspended in injectable-grade normal saline.

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
To assess the safety of the P. vivax IBSM model following inoculation of healthy participants.
大体时间:Time of inoculation with the challenge agent until at least 21 days after inpatient discharge

Incidence and severity of local and systemic AEs or SAEs.

Time of inoculation with the challenge agent until at least 21 days after inpatient discharge

次要结果测量

结果测量
措施说明
大体时间
To establish a dataset that may be used as a historical control in future interventional IBSM studies.
大体时间:From the time of inpatient admission to the time of discharge.

Demonstration of transmission in mosquito feeding assays among a requisite number of participants.

From the time of inpatient admission to the time of discharge.
To evaluate transmission of P. vivax to vector mosquitoes in the IBSM model by mosquito feeding assays.
大体时间:From the time of inpatient admission to the time of discharge.

Transmission of P. vivax to Anopheles spp. using mosquito feeding assays including direct feeding assays and/or membrane feeding assays as determined by the detection of oocysts following midgut dissection. Additional optional measures may include salivary gland dissection or detection by molecular methods.

From the time of inpatient admission to the time of discharge.
To establish an appropriate challenge agent dose for use in P. vivax IBSM studies.
大体时间:From the time of inoculation until the time of inpatient admission. Expected to be approximately day 9.

A suitable dose of challenge agent which generates parasitemia in a reliable and timely manner as determined by the investigator.

From the time of inoculation until the time of inpatient admission. Expected to be approximately day 9.

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:Joel A Goldberg, M.D.、National Institute of Allergy and Infectious Diseases (NIAID)

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。

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)

2024年11月26日

初级完成 (估计的)

2027年11月26日

研究完成 (估计的)

2027年11月26日

研究注册日期

首次提交

2024年9月20日

首先提交符合 QC 标准的

2024年9月20日

首次发布 (实际的)

2024年9月23日

研究记录更新

最后更新发布 (实际的)

2026年10月26日

上次提交的符合 QC 标准的更新

2026年10月23日

最后验证

2026年10月22日

更多信息

与本研究相关的术语

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)?

未定

IPD 计划说明

De-identified data in an NIH-funded or approved public repository.@@@- De-identified data in another public repository.@@@- Identified data in the Biomedical Translational Research Information System (automatic for activities in the CC).@@@- De-identified or identified data with approved outside collaborators under appropriate agreements.@@@- De-identified data in publications and/or public presentations.@@@Data will be shared at the time of or shortly after publication.

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

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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