A Phase 1 Clinical Trial To Evaluate The Safety and Infectivity Of Direct Venus Inoculation of Aseptic, Purified, Cryopreserved Plasmodium Falciparum 7G8 And NF54 Challenge Strains (PfSPZ) in a Head-To-Head Comparative Study
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 发起方
- 主要终点
- Difference in the pre-patent period
研究概览
简要总结
A comparison of Malaria events (symptoms and signs of malaria) experienced by subjects infected with PfSPZ Challenge (NF54) vs. PfSPZ Challenge (7G8).
详细描述
The single center study is designed as a double-blind, randomized, placebo-controlled CHMI trial with 2 parallel test groups to directly compare clinical and laboratory characteristics of the NF54 and 7G8 strains of PfSPZ Challenge. This study will also evaluate signatures of and time to parasitemia by multiple methods and evaluate physiologic status data collected by non-invasive wearable monitors before and during Plasmodium falciparum infection to characterize and trend physiologic changes appearing prior to the onset of parasitemia.
PfSPZ Challenge (aseptic, purified, cryopreserved, infectious Plasmodium falciparum sporozoites) or normal saline will be administered by direct venous inoculation (DVI) by 25-gauge needle and syringe to healthy malaria naïve adults.
Data generated from samples collected for biomarker assay analysis will be useful for developing predictive models to evaluate the efficacy of malaria vaccine candidates.
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
- Triple (Participant, Care Provider, Investigator)
盲法说明
double-blind, randomized, placebo-controlled trial
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
- •Adults (male or non-lactating, non-pregnant female)
- •Between the ages of 18 and 45 (inclusive) at the time of enrollment
- •Body weight equal to or greater than 110 lbs
- •Available and willing to participate for duration of study
- •Able and willing to provide a written informed consent
- •Able to complete an Assessment of Understanding with a score of at least 80% correct
- •In good general health with no clinically significant health problems as established by medical history, physical examination, and laboratory screening
- •Sexually active females, unless surgically sterile or at least 1 year post-menopausal, must use an effective method of avoiding pregnancy (Section 5.4.5.3) from 14 days prior to CHMI and agree to continue using such precautions during the study until at least 2 months after CHMI
- •If female subjects are unable to bear children due to menopause or have had a procedure performed (e.g. tubal ligation or hysterectomy), a medical note from a physician is required
- •If post-menopausal, subjects must have experienced at least 1 year of amenorrhea and provide a medical note from her physician documenting this medical history
- •Agree not to travel to a malaria endemic area during the course of the study
- •Agree to refrain from blood donation from the time of CHMI and for 3 years following CHMI
- •Must be willing to take anti-malarial treatment after CHMI
- •Must agree to stay in a pre-determined hotel near the NMRC CTC from approximately 7 days after CHMI until antimalarial treatment is completed or through 18 days post CHMI
- •For active-duty military personnel, documentation of their command's approval to participate
排除标准
- •Pregnant (positive urine pregnancy test) or nursing at screening or plans to become pregnant or nurse at any period from the time of enrollment through 56 days after CHMI.
- •Receipt of any investigational malaria vaccine
- •Any history of malaria infection
- •Travel to a malaria endemic region within 6 months of enrollment or during the study (from enrollment through 2 months after CHMI)
- •History of long-term residence (>5 years) in an area known to have significant transmission of P falciparum (http://www.cdc.gov/malaria/map/)
- •History of clinically significant contact dermatitis
- •Seropositive for the human immunodeficiency virus (HIV), hepatitis C virus (HCV), and/or hepatitis B surface antigen (HBsAg)
- •Positive sickle cell screening test, including evidence of sickle cell trait or sickle cell anemia (due to its effect on subject's susceptibility to malaria)
- •History of thalassemia or thalassemia trait (due to its effect on subject's susceptibility to malaria)
- •Participation in any clinical study involving another investigational vaccine, drug, or other products within 60 days prior to enrollment or plan to participate in such a clinical study during or within 1 month following the active study phase of the study (from the day enrollment through 2 months after CHMI)
- •Allergy to any component of the PfSPZ Challenge formulation, Malarone® (atovaquone-proguanil), and/or Coartem® (artemether-lumefantrine)
- •History of porphyria
研究组 & 干预措施
Group 1 - PfSPZ, (NF54) strain
Group 1 (N=9) will receive PfSPZ Challenge (NF54) A one-time dose of 3,200 aseptic, purified, cryopreserved, non-attenuated Plasmodium falciparum (Pf) NF54 sporozoites (Pf SPZ Challenge) Mode of administration: Direct venous inoculation (DVI) through a 25 gauge needle and syringe
干预措施: atovaquone-proguanil (Drug)
Group 2 - PfSPZ, (7G8) strain
Group 2 (N=9) will receive PfSPZ Challenge (7G8) A one-time dose of 3,200 aseptic, purified, cryopreserved, non-attenuated Plasmodium falciparum 7G8 sporozoites (Pf SPZ Challenge) Mode of administration: Direct venous inoculation (DVI) through a 25 gauge needle and syringe
干预措施: atovaquone-proguanil (Drug)
结局指标
主要结局
Difference in the pre-patent period
时间窗: 29 days
The difference in the time of first malaria event (symptom or sign of malaria),in subjects infected with PfSPZ Challenge (NF54) vs. PfSPZ Challenge (7G8)
Difference in the total number of malaria events
时间窗: 29 days
The difference in the total number of Grade 2 or greater malaria events (symptoms and signs of malaria) experienced by subjects infected with PfSPZ Challenge (NF54) vs PfSPZ Challenge (7G8)
次要结局
- Determine differences in pre-patent periods(29 days)
- Determine differences in the growth rate of parasites(29 days)