Randomized, Double-blind, Placebo-controlled Clinical Trial to Assess Safety, Tolerability and Protective Efficacy of PfSPZ Vaccine in 1-12 Year-old Gabonese Children Naturally Exposed to Malaria Parasites
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Sanaria Inc.
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- The occurrence and frequency of adverse events (AEs)
研究概览
简要总结
This study is a single site, randomized, double-blind, placebo-controlled trial. The trial will assess the safety, tolerability, immunogenicity and vaccine efficacy (VE) of PfSPZ Vaccine in Gabonese children that are naturally exposed to malaria parasites. Healthy children aged 1- 12 years living in the surrounding areas of Lambaréné and/or Fougamou Province in Gabon will be eligible for participation.
详细描述
The trial will be performed in 200 healthy Gabonese children, recruited across three age-strata: 7-12, 3-6 and 1-2 years (12-35 months). Within each age-stratum, volunteers will be randomized in a 2:1 ratio to receive three doses via direct venous inoculation (DVI) of either PfSPZ Vaccine (0.9x10^6) or normal saline (NS) on days 0, 7 and 28 respectively; a minimum of 40 and a maximum of 100 volunteers are included in each of these age-strata.
In total, approximately 133 children will receive PfSPZ Vaccine and approximately 67 children will receive placebo. Randomization will be stratified by age-stratum, using permuted blocks of randomized size (3, 6, or 9). The start of inclusion into each age-stratum will be staggered, such that immunization of the first 3-6-year-olds will not commence until two weeks after start of immunization in the first 7-12-year-olds, and immunizations in the first 1-2-year-olds will not commence until two weeks after start of immunization in the first 3-6-year-olds. All volunteers will receive presumptive treatment with artemether-lumefantrine two weeks prior to final immunization (day 14). All volunteers will receive presumptive treatment with age-standardized 3-day course of oral artemether-lumefantrine (AL) ~two weeks prior to first immunization and again two weeks prior to final immunization.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 1 Year 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy children aged 1 to 12 years
- •Provision of written informed consent of a legal representative of age 18 or above and provision of informed assent by participants in concordance with Gabonese national guidelines.
- •Able and willing to comply with all study requirements
- •Residence in the area throughout the study period
- •Household member reachable by mobile phone during the immunization phase
排除标准
- •Receipt of an investigational product in the 30 days preceding enrollment
- •Prior receipt of a malaria vaccine
- •Immunization with more than 3 other vaccines or at least on elive vaccine within the past four weeks
- •Use of immunoglobulins or blood products within 3 months prior to immunization with the investigational product
- •Known or suspected HIV infection or any other immunosuppressive state
- •Positive for hepatitis B surface antigen (HBs-antigen)
- •Seropositive for hepatitis C virus (antibodies to HCV)
- •A hemoglobin concentration <9 g/dl (applies at enrollment only)
- •History of non-febrile or atypical febrile seizures
- •Pregnancy or lactation
- •Any other significant disease, disorder or finding which, in the opinion of the investigator, may significantly increase the risk to the child because of participation in the study or impair interpretation of the study data
结局指标
主要结局
The occurrence and frequency of adverse events (AEs)
时间窗: From the time of each PfSPZ Vaccine immunization until 7 days after each dose
The occurrence and frequency of Grade 3 solicited adverse AEs (related or unrelated) after vaccination
The occurrence and frequency of AEs
时间窗: From the time of first PfSPZ Vaccine immunization until 28 days after the last dose
The occurrence and frequency of Grade 3 unsolicited adverse AEs (related or unrelated) after vaccination
Proportion of volunteers who become parasitemic will be recorded, detected by Thick Blood Smear (TBS) microscopy
时间窗: From 2 weeks to 6 months after the third PfSPZ Vaccine immunization
Time to event and proportional analysis of episodes of P. falciparum parasitemia, detected actively or passively by TBS microscopy. Vaccine efficacy will be measured in the mITT population.
Proportion of volunteers who become parasitemic with temperature ≥37.5°C or history of fever
时间窗: From 2 weeks to 6 months after the third PfSPZ Vaccine immunization
Time to event and proportional analysis of episodes of P. falciparum parasitemia with temperature ≥37.5°C or history of fever within the last 24 hours (P. falciparum malaria with clinical manifestations). Vaccine efficacy against P. falciparum malaria with clinical manifestations will be measured in the mITT population using hierarchical testing; the secondary will only be tested when the primary endpoint shows a significant difference.
The occurrence and frequency of serious adverse events (SAEs)
时间窗: Around 27 months (from day of first immunization through study completion)
The occurrence and frequency of SAEs (related or unrelated) after vaccination
次要结局
- The occurrence of all related solicited AE(From the time of each PfSPZ Vaccine immunization until 7 days after each dose)
- The occurrence of all related unsolicited AEs(From the time of first PfSPZ Vaccine immunization until 28 days after the last dose)