A Phase 1/2, Randomized, Controlled Open-label Trial to Evaluate the Safety and Immunogenicity of the rVSVΔG-ZEBOV-GP Ebola Virus Vaccine Candidate in Healthy Children Aged 1 to 12 Years and in Their Relatives Living in Lambaréné, Gabon
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Concentration of viral vector in blood, saliva and urine in vaccinees
研究概览
简要总结
LA rVSVΔG-ZEBOV-GP -02-PED is a Phase 1/2, randomized, controlled open label trial. The LA rVSVΔG-ZEBOV-GP -02-PED trial aims primarily to assess the clinical significance of shedding of the rVSV RNA following vaccination with the rVSVΔG-ZEBOV-GP vaccine in children. The vaccine doses of ≥7.8 x 107 pfu will be evaluated and compared to vaccination with varicella vaccine as a control. In addition, the closest contact persons of the vaccinees will be monitored for possible transmission of the viral vaccine vector.
The study will enroll children of two age groups living in Lambaréné, Gabon. Children will be followed-up for 12 months post vaccination.
The 1-2 closest contact persons of each participant will be involved in the monitoring of rVSV transmission. They will be followed until day 56 post- vaccination of their children/ sibling.
详细描述
LA-rVSVΔG-ZEBOV-GP -02-PED is a Phase 1/2, randomized, controlled, open label, trial and is designed to generate further safety, tolerability and immunogenicity data of the 7.8 x 107 PFU rVSVΔG-ZEBOV-GP vaccine in children aged 1 -12 years living in a sub-Saharan Africa. The study will enroll participants into two age groups. A total of 120 children will be enrolled and followed-up for 12 months post injection. In addition, a maximum of 240 relatives of the study participants will be enrolled to assess the transmission of the rVSVΔG-ZEBOV-GP vaccine.
Group 1: 60 participants aged 6-12 years will be randomized in group 1. 40 participants will receive a single intramuscular dose of 7.8 x 107 pfu rVSVΔG-ZEBOV-GP vaccine. 20 participants will receive a single subcutaneous dose of varicella vaccine The participants will be allocated to each treatment at a ratio of 2:1 respectively Group 2: 60 participants aged 1 -5 years will be randomized into group 2. 40 will receive a single intramuscular dose of 7.8 x 107 pfu of rVSV-ZEBOV vaccine. 20 participants will receive a single subcutaneous dose of varicella vaccine The participants will be allocated to each treatment at a ratio of 2:1 respectively
Vaccinations will start in group 2 after the first 10 participants of group 1 have completed the day 28 post vaccination visit and the SMC has done a review of safety data until that point.
For each vaccinee there will be a 365 -day period of follow-up after vaccination. The contact persons of the vaccinees will be followed-up until day 56 after the vaccination of their relative.
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
- None
盲法说明
The vaccine doses of ≥7.8 x 107 pfu will be evaluated and compared to vaccination with varicella vaccine as a control. In addition, the closest contact persons of the vaccinees will be monitored for possible transmission of the viral vaccine vector.
The study will enroll children of two age groups living in Lambaréné, Gabon. Children will be followed-up for 12 months post vaccination.
The 1-2 closest contact persons of each participant will be involved in the monitoring of rVSV transmission.
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 (inclusive) at the time of inclusion.
- •Willingness of parent or legal guardian to provide written informed consent prior to screening procedures.
- •Willingness of the relatives of the participant to provide written informed consent if they are ≥ 18 years (or an assent when they are 13 to 17 years old).
- •Available, able, and willing to participate in all study visits and procedures
排除标准
- •History of severe local or systemic reactions to any vaccination or a history of severe allergic reactions, or known allergy to the components of the vaccines.
- •Ongoing participation in another clinical trial
- •Participation in previous Ebola vaccine trials
- •Receipt of a licensed vaccine within 14 days of planned study immunization (30 days for live vaccines)
- •Presence of any febrile illness (fever >38°C) or any moderate to severe illness within one week prior to vaccination;
- •Administration of immunoglobulins and/or any blood products within the 120 days preceding study entry or planned administration during the study period
- •Any other significant finding that in the opinion of the investigator would increase the risk of the individual having an adverse outcome from participating in this study.
研究组 & 干预措施
the rVSVΔG-ZEBOV-GP vaccine
Participants of the experimental arm will receive a single intramuscular dose of ≥7.8 x 107 pfu of the rVSVΔG-ZEBOV-GP vaccine. In total, 80 participants will receive the experimental vaccine: 40 participants aged 6-12 years and 40 aged 1-5 years.
干预措施: rVSVΔG-ZEBOV-GP, V920 (Biological)
The Chikenpox or Varicella (Varilix) vaccine
The control arm consists of the chickenpox vaccine. Forty children will receive a single subcutaneous dose of Varilix, the active comparator vaccine, 20 aged 6-12 years and 20 aged 1-5 years
干预措施: Chikenpox or Varicella vaccine (VARILRIX) (Biological)
Fibre and equilibrate diet
Participants were assigned to receive two meals daily ( breakfast and lunch) for 21 days. About 30 children are randomly assigned to fibre and equilibrate diet.
干预措施: Fibre and equilibrate breakfast and lunch (Dietary Supplement)
Active detection and treatment of pathogens according to standard of care
The following pathogens: P. falciparum, Ascaris lumbricoides, Trichuris trichiura, Necator americanus, intestinal protozoa, BG+, BG- colonies and pathogens, SARS-CoV2 are actively detected and treated according to the standard of care every month. About 30 children are randomly assigned to this arm.
干预措施: Active detection and treatment of pathogens (Diagnostic Test)
Diet plus Active detection and treatment of pathogens according to standard of care
Participants were assigned to receive two meals daily ( breakfast and lunch) for 21 days and concomitantly assigned to active detection of P. falciparum, Ascaris lumbricoides, Trichuris trichiura, Necator americanus, intestinal protozoa, BG+, BG- colonies and pathogens, SARS-CoV2 every month. About 30 children are assigned to receive combined interventions
干预措施: Fibre and equilibrate breakfast and lunch plus Active detection and treatment of pathogens (Combination Product)
No diet and no pathogen detection
About 30 children received no diet and no active detection of pathogens
干预措施: Placebo (Other)
结局指标
主要结局
Concentration of viral vector in blood, saliva and urine in vaccinees
时间窗: at days 0, 1, 2/3, 7, 14 and 28
Concentration of rVSVΔG-ZEBOV-GP in blood, urine, or saliva as detected by RT-PCR and expressed as copy number in vaccinees
Prevalence and relative risk of sollicited adverse events in vaccinees
时间窗: until day 14 post vaccination
Proportion (percent) of participants experiencing sollicited adverse events in vaccinees groups
Prevalence and relative risk of unsolicited adverse events and serious adverse events in vaccinees
时间窗: until day 28 after vaccination
Proportion (percent ) of participant experiencing unsollicited adverse event (AEs) and serious adverse events (SAEs) and relative risk of AEs and SAEs in participant by vaccine groups
次要结局
- Prevalence and relative risk of serious adverse events(until day 365)
- Transmission intensity of the viral vector in blood, saliva and urine among the the relatives of the vaccinees(days 0, 1, 3, 14, 28, 56)
- Titres of ZEBOV-GP-specific binding antibody(days 0, 1, 3, 14, 21, 28, 56, 84, 180, 365)
- Affinity/Avidity of antibody induced by vaccination(days 28 and 180)
- Concentration of IL-1RN (IL-1Ra), IL-6, TNF-α, IL-10, MCP-1/CCL2, and MIP-1β/CCL4(days 0, 1 and 2 or 3)
- Prevalence of miRNAs(at days 0, 1, 2/3, 7)
- Concentration of Lipids, glutamine, Alanine, Aspargine(at day 0, day 1, day 2/3 and day 7)
- Concentrations Nitric oxides species(days 0, 1, 2/3, 7, 28, 56, 90, 180, 365)
- Concentration of metabolites of gut bacteria(days 0, 7, 28, 56, 90)
- Titres of antibody induced by diphtheria, tetanus, Bordetella, poliomyelitis, hepatitis B, measles, yellow fever ( EPI vaccines)(days 0, 7, 14, 28, 90, 180, 365)
- Concentration of bystander cytokines(days 0, 1, 2/3, 7, 28, 90)
研究者
Selidji Todagbe Todagbe Agnandji
Director
Centre de Recherche Médicale de Lambaréné