NCT01771848已完成1 期
A Study to Optimize Controlled Human Malarial Infection by Injection of Plasmodium Falciparum Sporozoites in Non-Immune Adults
适应症
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Sanaria Inc.
- 入组人数
- 36
- 试验地点
- 4
- 主要终点
- Infectivity of the administration regimens
研究概览
简要总结
The study is designed to establish the best dose to safely infect healthy individuals with Plasmodium falciparum sporozoites (PfSPZ) by injection.
The goal of this study is to achieve infections in human volunteers with infection rates of 100% and pre-patent periods of less than 12 days.
详细描述
This is an single center,open label, escalated and controlled human pilot study to optimize CHMI (controlled human malaria infection) administered by PfSPZ Challenge. The study was designed with an escalated dosing design in order to answer two questions:
- Does altering the volume of administration, alter infectivity of PfSPZ Challenge administered IM (intramuscular)? By varying the volume of inoculation of the 2,500 dose of PfSPZ administered IM we try to increase infection rates and decrease pre-patent period (Part A).
- When administered in the optimum volume determined in Part A, does increasing the dose increase the infectivity and decrease the pre-patent period of PfSPZ Challenge? By increasing the dose of PfSPZ we try to decrease the pre-patent period at the higher dose (Part B).
Besides increasing the infectivity rate, we aim to reduce the pre-patent period to ~11 days.
In Part A of the trial, the volume of inoculation will vary in order to identify the optimal volume needed for a dose of 2,500 PfSPZ to induce the greatest infection rate (defined as highest percentage of infected volunteers and shortest pre-patent period.)
The outcome variables of part A are:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy adults aged 18 to 45 years
- •Able and willing (in the Investigator's opinion) to comply with all study requirements
- •Women only: must agree to practice continuous effective contraception for the duration of the study (such as hormonal contraceptives, condom or intrauterine device (IUD)).
- •Agreement to refrain from blood donation in Spain during the course of the study and thereafter
- •Agree not to participate in another study with an investigational product during the course of this study
- •Written informed consent to undergo CHMI
- •Reachable (24/7) by mobile phone during the whole study period
- •Willingness to take a curative anti-malarial regimen
- •Agreement to stay overnight for observation during the period of intensive follow-up post-challenge if required
- •Answer all questions on the informed consent quiz correctly
- •A body mass index < 35
排除标准
- •History of P. falciparum malaria
- •Travel to malaria endemic region before the participation in the study with positive P. falciparum serology at screening.
- •Use of systemic antibiotics with known antimalarial activity within 30 days of study enrolment (e.g. trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin, erythromycin, fluoroquinolones, or azithromycin)
- •Is using and intends to continuing using a medication known to cause drug reactions with chloroquine or Malarone®, such as cimetidine, metoclopramide, antacids or kaolin (antacids and kaolin can be administered at least 4 hours from intake of chloroquine)
- •Receipt of an investigational product in the 30 days preceding enrolment, or planned receipt during the study period
- •Prior receipt of an investigational malaria vaccine
- •Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection, asplenia, recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed)
- •Use of immunoglobulins or blood products within 3 months prior to enrolment
- •Presence of sickle cell anemia, sickle cell trait, thalassemia or thalassemia trait
- •Pregnancy, lactation or intention to become pregnant during the study
- •A history of allergic disease or reactions likely to be exacerbated by malaria
- •Contraindications or known allergy to the first-line anti-malarial medications: chloroquine, atovaquone/proguanil and artemether/lumefantrine.
- •History of cancer (except successfully treated and cured basal cell carcinoma of the skin and cervical carcinoma in situ)
- •History of serious psychiatric condition that may affect participation in the study
- •Any other serious chronic illness requiring hospital specialist supervision
- •Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 30g (men) or 20g (women) per day
- •Suspected or known injecting drug abuse in the 5 years preceding enrolment
- •Seropositive for hepatitis B surface antigen (HBsAg)
- •Seropositive for hepatitis C virus (antibodies to HCV)
- •An estimated, ten year risk of fatal cardiovascular disease of ≥5%, as estimated by the Systematic Coronary Risk Evaluation (SCORE) system [42]
- •Abnormal electrocardiogram on screening: pathologic Q wave and significant ST-T wave changes, left ventricular hypertrophy, non-sinus rhythm except isolated premature atrial contractions, right or left bundle branch block, advanced A-V heart block (secondary or tertiary)
- •Volunteers unable to be closely followed for social, geographic or psychological reasons
- •Any clinically significant abnormal finding on biochemistry or haematology blood tests, urinalysis or clinical examination
- •Any other significant disease, disorder or finding which, in the opinion of the Investigator, may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data
结局指标
主要结局
Infectivity of the administration regimens
时间窗: Study day 6 to day 90 post challenge
For each trial stage (A and B) the infectivity of the three administration regimens will be assessed by thick film microscopy and q-PCR for P. falciparum DNA. The time from parasite inoculation to first detection of blood stage parasitemia will be assessed by thick blood film microscopy.
次要结局
- Safety of PfSPZ Challenge(All study visits until day 90 post challenge)
研究者
研究点 (4)
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