A Staged Phase I/II Observer-blind, Randomised, Controlled, Multi-country Study to Evaluate the Safety, Reactogenicity, and Immune Responses to the GVGH altSonflex1-2-3 Vaccine Against S. Sonnei and S. Flexneri, Serotypes 1b, 2a, and 3a, in Adults in Europe (Stage 1) Followed by Age De-escalation From Adults to Children and Infants, and Dose-finding in Infants in Africa (Stage 2)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 551
- 试验地点
- 3
- 主要终点
- Number of adults 18 to 50 years of age in Europe with solicited administration site events
研究概览
简要总结
The aim of the current clinical study was to evaluate, for the first time in humans (FTIH), the safety and immunogenicity of the altSonflex1-2-3 candidate vaccine against S. sonnei and S. flexneri serotypes 1b, 2a, and 3a. The vaccine was first administered to adults 18 to 50 years of age in Europe. Subsequently, the vaccine was administered to a shigellosis-endemic population in Africa, first to adults 18 to 50 years of age, then to children 24 to 59 months of age, and finally to infants 9 months of age. Infants also received a third vaccination. Three different doses of the vaccine [low, medium, and high amounts of antigen] were evaluated using an age de-escalation approach (from the least vulnerable adult population to the most vulnerable paediatric population). The results of this study allowed the selection of the most appropriate dose for further vaccine development in infants 9 months of age, which was the main target age group for this vaccine.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Observer blind
入排标准
- 年龄范围
- 9 Months 至 50 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •All participants:
- •Participants and/or participants' parent(s)/legally acceptable representative(s) (LARs), who, in the opinion of the investigator, could and would comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits).
- •Written or witnessed/thumb-printed informed consent was obtained from the participant/parent(s)/LAR(s) of the participant prior to the performance of any study-specific procedure.
- •Healthy participants, as established by medical history, clinical examination, and laboratory assessment.
- •Participants who satisfied all screening requirements.
- •Participants who were seronegative for hepatitis B and hepatitis C.
- •Participants who were negative for human leukocyte antigen B27 (HLA-B27).
- •Adults 18 to 50 years of age:
- •A male or female between, and including, 18 and 50 years of age at the time of the first study intervention administration.
- •Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause.
- •Female participants of childbearing potential may be enrolled in the study, if the participant:
- •- has practiced adequate contraception for 1 month prior to study intervention administration, and
- •- has a negative pregnancy test on the day of study intervention administration, and
- •has agreed to continue adequate contraception during the entire treatment period and for 1 month after completion of the study intervention administration series.
- •Participants seronegative for human immunodeficiency virus (HIV).
- •Children 24 to 59 months of age:
- •A male or female between, and including, 24 and 59 months of age at the time of first vaccination.
- •A normal nutritional Z score (-2 standard deviations or greater).
- •Participants who had previously completed routine childhood vaccinations to the best knowledge of the participant's parent(s)/LAR(s).
- •Participants who were born after a gestation period of ≥37 weeks.
- •Participants who were seronegative for HIV.
- •Infants 9 months of age:
- •A male or female 9 months of age at the time of first vaccination.
- •A normal nutritional Z score (-2 standard deviations or greater).
- •Participants who had previously completed routine childhood vaccinations to the best knowledge of the participant's parent(s)/LAR(s).
- •Participants who were born after a gestation period of >=37 weeks.
- •Participants who were negative for HIV, as confirmed by deoxyribonucleic acid (DNA) polymerase chain reaction (PCR) testing.
排除标准
- •All participants:
- •Known exposure to Shigella during the lifetime of the participant, as confirmed during interview with the participant or documented by patient records (e.g., history of microbiologically confirmed Shigella infection), recent travel* (within 2 years) to a country where Shigella or other enteric infections are endemic, or recent occupation* (within 3 years) involving Shigella species.
- •Exclusion due to travel or occupation was applicable only to adults 18 to 50 years of age in Europe (Stage 1).
- •Progressive, unstable, or uncontrolled clinical conditions.
- •A history (known or suspected) of any reaction or hypersensitivity likely to be exacerbated by any component of the study vaccine.
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing was required).
- •Hypersensitivity, including allergy, to medicinal products or medical equipment whose use was foreseen in this study.
- •Clinical conditions representing a contraindication to IM vaccination and blood draws.
- •Any behavioural or cognitive impairment or psychiatric disease that, in the opinion of the investigator, might have interfered with the participant's ability to participate in the study.
- •Acute disease and/or fever (defined as temperature ≥38.0°C) at the time of enrolment*.
- •The participant could still be enrolled into the study at a time when the acute disease and/or fever had resolved.
- •Any clinically significant haematological and/or biochemical laboratory abnormality.
- •A confirmed positive COVID-19 test during the period starting 30 days before the first administration of study vaccines (Day -30 to Day 1).
- •Any other clinical condition that, in the opinion of the investigator, might have posed additional risk to the participant due to participation in the study.
- •Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
- •Prior receipt of an experimental Shigella vaccine or live Shigella challenge.
- •Use of any investigational or non-registered product (drug, vaccine, or medical device)* other than the study vaccine during the period starting 30 days before the first dose of study intervention (Day -30 to Day 1), or planned use during the study period.
- •Use of herbs and traditional treatments was not considered an exclusion criterion.
- •Administration of a vaccine not foreseen* by the Study Protocol during the period starting at -21 days before the first dose (-28 days in the case of live vaccines) and ending after the last dose of study intervention administration**.
- •Vaccines allowed by the Protocol included flu and COVID-19 vaccines in all participants and EPI vaccines in children and infants.
- •*In case of emergency mass vaccination, the time period above could be reduced.
- •Concurrent participation in another clinical study, at any time during the study period, in which the participant had been or would be exposed to an investigational or non-investigational intervention (drug or invasive medical device).
- •Any study personnel or immediate dependents, family, or household members.
- •Adults 18 to 50 years of age:
- •Acute or chronic illness, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by physical examination or laboratory screening tests.
- •Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first vaccine study intervention. For corticosteroids, this meant a prednisone equivalent ≥20 mg/day for adult participants. Inhaled and topical steroids were allowed.
- •Pregnant or lactating females.
- •Females planning to become pregnant or planning to discontinue contraceptive precautions.
- •A history of or current chronic alcohol consumption and/or drug abuse.
- •Adults 18 to 50 years of age and children 24 to 59 months of age:
- •Administration of immunoglobulins and/or any blood products or plasma derivatives, or bone marrow transplantation, during the period starting 3 months before the first dose of study vaccine or planned administration during the study period.
- •Children 24 to 59 months of age and infants 9 months of age:
- •Acute or chronic clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by physical examination or laboratory screening tests.
- •Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first vaccine dose. For corticosteroids, this meant prednisone ≥0.5 mg/kg/day or 20 mg/day, whichever was the maximum dose for paediatric participants. Inhaled and topical steroids were allowed.
- •A child in care.
- •Infants 9 months of age:
- •Administration of immunoglobulins and/or any blood products or plasma derivatives, or bone marrow transplantation, from birth or planned administration during the study period.
研究组 & 干预措施
Stage 2 Adults: Control
African participants 18-50 years of age were randomized to receive 1 dose of MENVEO as comparator on Day 1 and 1 dose of BOOSTRIX as comparator Day 85.
干预措施: Menveo (Biological)
Stage 2 Adults: Control
African participants 18-50 years of age were randomized to receive 1 dose of MENVEO as comparator on Day 1 and 1 dose of BOOSTRIX as comparator Day 85.
干预措施: Boostrix (Combination Product)
Stage 1 Adults: altSonflex1-2-3 High Dose Group 1
European participants 18-50 years of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1 and Day 85. High dose of altSonflex1-2-3 contained 15 micrograms (µg) of O-antigen (OAg) each Shigella serotype (S. sonnei, S. flexneri 1b, S. flexneri 2a, S. flexneri 3a).
干预措施: AltSonflex1-2-3 High Dose (Biological)
Stage 1 Adults: altSonflex1-2-3 High Dose Group 2
European participants 18-50 years of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1 and Day 169. High dose of altSonflex1-2-3 contained 15 µg OAg of each Shigella serotype (S. sonnei, S. flexneri 1b, S. flexneri 2a, S. flexneri 3a).
干预措施: AltSonflex1-2-3 High Dose (Biological)
Stage 1 Adults: Placebo Group
European participants 18-50 years of age were randomized to receive 1 dose of Placebo on Day 1 and on Day 85 or 169. All participants in Step 1 that received placebo were pooled, as pre-specified in Statistical Analysis Plan.
干预措施: altSonflex Placebo (Drug)
Stage 2 Adults: altSonflex1-2-3 High Dose
African participants 18-50 years of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1 and Day 85. High dose of altSonflex1-2-3 contained of 15 µg OAg of each Shigella serotype (S. sonnei, S. flexneri 1b, S. flexneri 2a, S. flexneri 3a).
干预措施: AltSonflex1-2-3 High Dose (Biological)
Stage 2 Children: altSonflex1-2-3 Medium Dose
African participants 24-59 months of age were randomized to receive a medium dose of altSonflex1-2-3 on Day 1 and Day 85. Medium dose of altSonflex1-2-3 contained 7.5 µg OAg of each Shigella serotype (S. sonnei, S. flexneri 1b, S. flexneri 2a, S. flexneri 3a).
干预措施: AltSonflex1-2-3 Medium Dose (Biological)
Stage 2 Children: altSonflex1-2-3 High Dose
African participants 24-59 months of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1 and Day 85. High dose of altSonflex1-2-3 contained 15 µg OAg of each Shigella serotype (S. sonnei, S. flexneri 1b, S. flexneri 2a, S. flexneri 3a).
干预措施: AltSonflex1-2-3 High Dose (Biological)
Stage 2 Children: Control
African participants 24-59 months of age were randomized to receive 1 dose of MENVEO as comparator on Day 1 and 1 dose of TYPHIM VI as comparator on Day 85.
干预措施: Typhim-Vi (Combination Product)
Stage 2 Infants safety cohort: altSonflex1-2-3 Low Dose
African participants 9 months of age were randomized to receive a low dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. The measles-rubella vaccine (MR-VAC) was administered on Day 29 and Day 281. Low dose of altSonflex1-2-3 contained 3.75 µg OAg of each Shigella serotype (S. sonnei, S. flexneri 1b, S. flexneri 2a, S. flexneri 3a).
干预措施: AltSonflex1-2-3 Low Dose (Biological)
Stage 2 Infants safety cohort: altSonflex1-2-3 Medium Dose
African participants 9 months of age were randomized to receive a medium dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was administered on Day 29 and Day 281. Medium dose of altSonflex1-2-3 contained 7.5 µg OAg of each Shigella serotype (S. sonnei, S. flexneri 1b, S. flexneri 2a, S. flexneri 3a).
干预措施: AltSonflex1-2-3 Medium Dose (Biological)
Stage 2 Infants safety cohort: altSonflex1-2-3 High Dose
African participants 9 months of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was administered on Day 29 and Day 281. High dose of altSonflex1-2-3 contained 15 µg OAg of each Shigella serotype (S. sonnei, S. flexneri 1b, S. flexneri 2a, S. flexneri 3a).
干预措施: AltSonflex1-2-3 High Dose (Biological)
Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose
African participants 9 months of age were randomized to receive a low dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was created to identify the preferred dose among low, medium and high doses. Low dose of altSonflex1-2-3 contained 3.75 µg OAg of each Shigella serotype (S. sonnei, S. flexneri 1b, S. flexneri 2a, S. flexneri 3a).
干预措施: AltSonflex1-2-3 Low Dose (Biological)
Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Medium Dose
African participants 9 months of age were randomized to receive a medium dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was created to identify the preferred dose among low, medium and high doses. Medium dose of altSonflex1-2-3 contained 7.5 µg OAg of each Shigella serotype (S. sonnei, S. flexneri 1b, S. flexneri 2a, S. flexneri 3a).
干预措施: AltSonflex1-2-3 Medium Dose (Biological)
Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Medium Dose
African participants 9 months of age were randomized to receive a medium dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was created to identify the preferred dose among low, medium and high doses. Medium dose of altSonflex1-2-3 contained 7.5 µg OAg of each Shigella serotype (S. sonnei, S. flexneri 1b, S. flexneri 2a, S. flexneri 3a).
干预措施: MR-Vac (Biological)
Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose
African participants 9 months of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was created to identify the preferred dose among low, medium and high doses. High dose of altSonflex1-2-3 contained 15 µg OAg of each Shigella serotype (S. sonnei, S. flexneri 1b, S. flexneri 2a, S. flexneri 3a).
干预措施: AltSonflex1-2-3 High Dose (Biological)
Stage 2 Children: Control
African participants 24-59 months of age were randomized to receive 1 dose of MENVEO as comparator on Day 1 and 1 dose of TYPHIM VI as comparator on Day 85.
干预措施: Menveo (Biological)
Stage 2 Infants safety cohort: altSonflex1-2-3 Low Dose
African participants 9 months of age were randomized to receive a low dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. The measles-rubella vaccine (MR-VAC) was administered on Day 29 and Day 281. Low dose of altSonflex1-2-3 contained 3.75 µg OAg of each Shigella serotype (S. sonnei, S. flexneri 1b, S. flexneri 2a, S. flexneri 3a).
干预措施: MR-Vac (Biological)
Stage 2 Infants safety cohort: altSonflex1-2-3 Medium Dose
African participants 9 months of age were randomized to receive a medium dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was administered on Day 29 and Day 281. Medium dose of altSonflex1-2-3 contained 7.5 µg OAg of each Shigella serotype (S. sonnei, S. flexneri 1b, S. flexneri 2a, S. flexneri 3a).
干预措施: MR-Vac (Biological)
Stage 2 Infants safety cohort: altSonflex1-2-3 High Dose
African participants 9 months of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was administered on Day 29 and Day 281. High dose of altSonflex1-2-3 contained 15 µg OAg of each Shigella serotype (S. sonnei, S. flexneri 1b, S. flexneri 2a, S. flexneri 3a).
干预措施: MR-Vac (Biological)
Stage 2 Infants safety cohort: Control
African participants 9 months of age were randomized to receive a dose of MENVEO as comparator on Day 1 and Day 85 and INFRANRIX HEXA as comparator on Day 253. MR-VAC was administered on Day 29 and Day 281.
干预措施: Menveo (Biological)
Stage 2 Infants safety cohort: Control
African participants 9 months of age were randomized to receive a dose of MENVEO as comparator on Day 1 and Day 85 and INFRANRIX HEXA as comparator on Day 253. MR-VAC was administered on Day 29 and Day 281.
干预措施: INFANRIX HEXA (Combination Product)
Stage 2 Infants safety cohort: Control
African participants 9 months of age were randomized to receive a dose of MENVEO as comparator on Day 1 and Day 85 and INFRANRIX HEXA as comparator on Day 253. MR-VAC was administered on Day 29 and Day 281.
干预措施: MR-Vac (Biological)
Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose
African participants 9 months of age were randomized to receive a low dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was created to identify the preferred dose among low, medium and high doses. Low dose of altSonflex1-2-3 contained 3.75 µg OAg of each Shigella serotype (S. sonnei, S. flexneri 1b, S. flexneri 2a, S. flexneri 3a).
干预措施: MR-Vac (Biological)
Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose
African participants 9 months of age were randomized to receive a high dose of altSonflex1-2-3 on Day 1, Day 85 and Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was created to identify the preferred dose among low, medium and high doses. High dose of altSonflex1-2-3 contained 15 µg OAg of each Shigella serotype (S. sonnei, S. flexneri 1b, S. flexneri 2a, S. flexneri 3a).
干预措施: MR-Vac (Biological)
Stage 2 Infants dose-finding cohort: Control
African participants 9 months of age were randomized to receive a dose of MENVEO as comparator on Day 1 and Day 85 and INFRANRIX HEXA as comparator on Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was created to identify the preferred dose among low, medium and high doses.
干预措施: Menveo (Biological)
Stage 2 Infants dose-finding cohort: Control
African participants 9 months of age were randomized to receive a dose of MENVEO as comparator on Day 1 and Day 85 and INFRANRIX HEXA as comparator on Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was created to identify the preferred dose among low, medium and high doses.
干预措施: INFANRIX HEXA (Combination Product)
Stage 2 Infants dose-finding cohort: Control
African participants 9 months of age were randomized to receive a dose of MENVEO as comparator on Day 1 and Day 85 and INFRANRIX HEXA as comparator on Day 253. MR-VAC was co-administered on Day 1 and Day 253. This cohort was created to identify the preferred dose among low, medium and high doses.
干预措施: MR-Vac (Biological)
结局指标
主要结局
Number of adults 18 to 50 years of age in Europe with solicited administration site events
时间窗: During 7 days after each study intervention administration (study interventions administered at Day 1 and Day 85/Day 169)
The solicited administration site events are pain, redness, and swelling.
Number of adults 18 to 50 years of age in Europe with unsolicited adverse events (AEs)
时间窗: During 28 days after each study intervention administration (study interventions administered at Day 1 and Day 85/Day 169)
An unsolicited AE is an AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited adverse event.
Number of adults 18 to 50 years of age in Europe with deviations from normal values of haematological, renal, and hepatic panel test results at Day 92/Day 176 (7 days after the second study intervention administration)
时间窗: At Day 92 (for ST1_Adults_Placebo_GR1 and ST1_Adults_Dose C_GR1 groups)/Day 176 (for ST1_Adults_Placebo_GR2 and ST1_Adults_Dose C_GR2 groups) (7 days after the second study intervention administration)
Panel tests include measures of leukocytes, erythrocytes, haemoglobin, haematocrit, platelets, eosinophils, basophils, neutrophils, monocytes, lymphocytes, creatinine, blood urea, sodium, potassium, aspartate aminotransferase (AST) and alanine aminotransferase (ALT).
Anti-serotype specific Shigella lipopolysaccharide (LPS)/O-Antigen (OAg) serum immunoglobulin G (IgG) geometric mean concentrations (GMCs) in infants 9 months of age in Africa
时间窗: At Day 281 (28 days after the third study intervention administration)
Anti-serotype specific Shigella LPS/OAg serum IgG GMCs are measured by GSK Vaccines Institute for Global Health (GVGH) enzyme-linked immunosorbent assay (ELISA) and expressed in ELISA units per milliliter (EU/mL) of serum.
Number of adults 18 to 50 years of age in Europe with solicited systemic events
时间窗: During 7 days after each study intervention administration (study interventions administered at Day 1 and Day 85/Day 169)
The solicited systemic event is fever. Fever is defined as temperature equal to or above (≥) 38.0°C. The preferred location for measuring temperature is the axilla for all participants.
Number of adults 18 to 50 years of age in Europe with serious adverse events (SAEs)
时间窗: During the entire study participation period [Day 1 to Day 113 (for ST1_Adults_Placebo_GR1 and ST1_Adults_Dose C_GR1 groups)/Day 197 (for ST1_Adults_Placebo_GR2 and ST1_Adults_Dose C_GR2 groups)
An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, results in abnormal pregnancy outcomes or any other situation based on appropriate medical or scientific judgement.
Number of adults 18 to 50 years of age in Africa with SAEs
时间窗: During the entire study participation (Day 1 to Day 113)
An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, results in abnormal pregnancy outcomes or any other situation based on appropriate medical or scientific judgement.
Number of adults 18 to 50 years of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results at Day 92 (7 days after the second study intervention administration)
时间窗: At Day 92 (7 days after the second study intervention administration)
Panel tests include measures of leukocytes, erythrocytes, haemoglobin, haematocrit, platelets, eosinophils, basophils, neutrophils, monocytes, lymphocytes, creatinine, blood urea, sodium, potassium, AST, and ALT.
Number of children 24 to 59 months of age in Africa with solicited administration site events
时间窗: During 7 days after each study intervention administration (study interventions administered at Day 1 and Day 85)
The solicited administration site events are pain, redness, and swelling.
Number of infants 9 months of age in Africa with solicited administration site events
时间窗: During 7 days after each study intervention administration (study interventions administered at Day 1, Day 85 and Day 253)
The solicited administration site events are pain, redness and swelling.
Number of infants 9 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results at Day 8 (7 days after the first study intervention administration)
时间窗: At Day 8 (7 days after the first study intervention administration)
Panel tests include measures of leukocytes, erythrocytes, haemoglobin, haematocrit, platelets, eosinophils, basophils, neutrophils, monocytes, lymphocytes, creatinine, blood urea, sodium, potassium, AST, and ALT.
Number of adults 18 to 50 years of age in Europe with deviations from normal values of haematological, renal, and hepatic panel test results at Day 8 (7 days after the first study intervention administration)
时间窗: At Day 8 (7 days after the first study intervention administration)
Panel tests include measures of leukocytes, erythrocytes, haemoglobin, haematocrit, platelets, eosinophils, basophils, neutrophils, monocytes, lymphocytes, creatinine, blood urea, sodium, potassium, aspartate aminotransferase (AST) and alanine aminotransferase (ALT).
Number of adults 18 to 50 years of age in Africa with unsolicited AEs
时间窗: During 28 days after each study intervention administration (study interventions administered at Day 1 and Day 85)
An unsolicited AE is an AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited adverse event.
Number of children 24 to 59 months of age in Africa with solicited systemic events
时间窗: During 7 days after each study intervention administration (study interventions administered at Day 1 and Day 85)
The solicited systemic event is fever. Fever is defined as temperature ≥ 38.0°C. The preferred location for measuring temperature is the axilla for all participants.
Number of adults 18 to 50 years of age in Africa with solicited administration site events
时间窗: During 7 days after each study intervention administration (study interventions administered at Day 1 and Day 85)
The solicited administration site events are pain, redness, and swelling.
Number of adults 18 to 50 years of age in Africa with solicited systemic events
时间窗: During 7 days after each study intervention administration (study interventions administered at Day 1 and Day 85)
The solicited systemic event is fever. Fever is defined as temperature ≥ 38.0°C. The preferred location for measuring temperature is the axilla for all participants.
Number of adults 18 to 50 years of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results at Day 8 (7 days after the first study intervention administration)
时间窗: At Day 8 (7 days after the first study intervention administration)
Panel tests include measures of leukocytes, erythrocytes, haemoglobin, haematocrit, platelets, eosinophils, basophils, neutrophils, monocytes, lymphocytes, creatinine, blood urea, sodium, potassium, AST, and ALT.
Number of children 24 to 59 months of age in Africa with unsolicited AEs
时间窗: During 28 days after each study intervention administration (study interventions administered on Day 1 and Day 85)
An unsolicited AE is an AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited adverse event.
Number of children 24 to 59 months of age in Africa with SAEs
时间窗: During the entire study participation period (Day 1 to Day 113)
An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in disability/incapacity or any other situation based on appropriate medical or scientific judgement.
Number of infants 9 months of age in Africa with solicited systemic events
时间窗: During 7 days after each study intervention administration (study interventions administered at Day 1, Day 85 and Day 253)
The solicited systemic event is fever. Fever is defined as temperature ≥ 38.0°C. The preferred location for measuring temperature is the axilla for all participants.
Number of infants 9 months of age in Africa with SAEs
时间窗: During the entire study participation period (Day 1 to Day 281)
An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in disability/incapacity or any other situation based on appropriate medical or scientific judgement.
Number of children 24 to 59 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results at Day 8 (7 days after the first study intervention administration)
时间窗: At Day 8 (7 days after the first study intervention administration)
Panel tests include measures of leukocytes, erythrocytes, haemoglobin, haematocrit, platelets, eosinophils, basophils, neutrophils, monocytes, lymphocytes, creatinine, blood urea, sodium, potassium, AST, and ALT.
Number of children 24 to 59 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results at Day 92 (7 days after the second study intervention administration)
时间窗: At Day 92 (7 days after the second study intervention administration)
Panel tests include measures of leukocytes, erythrocytes, haemoglobin, haematocrit, platelets, eosinophils, basophils, neutrophils, monocytes, lymphocytes, creatinine, blood urea, sodium, potassium, AST, and ALT.
Number of infants 9 months of age in Africa with unsolicited AEs
时间窗: During 28 days after each study intervention administration (study intervention administered at Day 1, Day 85 and Day 253)
An unsolicited AE is an AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited adverse event.
Number of infants 9 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results at Day 260 (7 days after the third study intervention administration)
时间窗: At Day 260 (7 days after the third study intervention administration)
Panel tests include measures of leukocytes, erythrocytes, haemoglobin, haematocrit, platelets, eosinophils, basophils, neutrophils, monocytes, lymphocytes, creatinine, blood urea, sodium, potassium, AST, and ALT.
Number of infants 9 months of age in Africa with deviations from normal values of haematological, renal, and hepatic panel test results at Day 92 (7 days after the second study intervention administration)
时间窗: At Day 92 (7 days after the second study intervention administration)
Panel tests include measures of leukocytes, erythrocytes, haemoglobin, haematocrit, platelets, eosinophils, basophils, neutrophils, monocytes, lymphocytes, creatinine, blood urea, sodium, potassium, AST, and ALT.
次要结局
- Number of adults 18 to 50 years of age in Africa achieving a GVGH ELISA level equivalent to ≥1:800 titer against S. sonnei LPS/OAg(At Day 1 and Day 85 (before each study intervention administration) and at Day 29 and Day 113 (28 days after each study intervention administration))
- Number of children 24 to 59 months of age in Africa achieving a GVGH ELISA level equivalent to ≥1:800 titer against S. sonnei LPS/OAg(At Day 1 and Day 85 (before each study intervention administration) and at Day 29 and Day 113 (28 days after each study intervention administration))
- Number of adults 18 to 50 years of age in Europe achieving a GVGH ELISA level equivalent to ≥1:800 titer against S. sonnei LPS/OAg(At Day 1 and Day 85/Day 169 (before each study intervention administration), at Day 15 (14 days after the first study intervention administration) and at Day 29 and Day 113/Day 197 (28 days after each study intervention administration))
- Number of adults 18 to 50 years of age in Europe achieving a GVGH ELISA level equivalent to ≥1:1600 titer against S. sonnei LPS/OAg(At Day 1 and Day 85/Day 169 (before each study intervention administration), at Day 15 (14 days after the first study intervention administration) and at Day 29 and Day 113/Day 197 (28 days after each study intervention administration))
- Anti-serotype specific Shigella LPS/OAg serum IgG GMCs in adults 18 to 50 years of age in Europe(At Day 1 and Day 85/Day 169 (before each study intervention administration), at Day 15 (14 days after the first study intervention administration) and at Day 29 and Day 113/Day197 (28 days after each study intervention administration))
- Anti-serotype specific Shigella LPS/OAg serum IgG GMCs in adults 18 to 50 years of age in Africa(At Day 1 and Day 85 (before each study intervention administration) and at Day 29 and Day 113 (28 days after each study intervention administration))
- Anti-serotype specific Shigella LPS/OAg serum IgG GMCs in children 24 to 59 months of age in Africa(At Day 1 and Day 85 (before each study intervention administration) and at Day 29 and Day 113 (28 days after each study intervention administration))
- Anti-serotype specific Shigella LPS/OAg serum IgG GMCs in infants 9 months of age in Africa(At Day 1, Day 85 and Day 253 (before each study intervention administration) and at Day 29, Day 113 and Day 281 (28 days after each study intervention administration))
- Number of infants 9 months of age in Africa achieving a GVGH ELISA level equivalent to ≥1:800 titer against S. sonnei LPS/OAg(At Day 1, Day 85 and Day 253 (before each study intervention administration) and at Day 29, Day 113 and Day 281 (28 days after each study intervention administration))
- Number of adults 18 to 50 years of age in Africa achieving a GVGH ELISA level equivalent to ≥1:1600 titer against S. sonnei LPS/OAg(At Day 1 and Day 85 (before each study intervention administration) and at Day 29 and Day 113 (28 days after each study intervention administration))
- Number of children 24 to 59 months of age in Africa achieving a GVGH ELISA level equivalent to ≥1:1600 titer against S. sonnei LPS/OAg(At Day 1 and Day 85 (before each study intervention administration) and at Day 29 and Day 113 (28 days after each study intervention administration))
- Number of children 24 to 59 months of age in Africa showing at least a 4-fold increase in anti-serotype specific Shigella LPS/OAg serum IgG concentrations, as measured by GVGH ELISA(At Day 29 and Day 113 (28 days after each study intervention administration) compared to Day 1 and Day 85 (baseline))
- Number of infants 9 months of age in Africa achieving a GVGH ELISA level equivalent to ≥1:1600 titer against S. sonnei LPS/OAg(At Day 1, Day 85 and Day 253 (before each study intervention administration) and at Day 29, Day 113 and Day 281 (28 days after each study intervention administration))
- Number of adults 18 to 50 years of age in Europe showing at least a 4-fold increase in anti-serotype specific Shigella LPS/OAg serum IgG concentrations, as measured by GVGH ELISA(At Day 15 (14 days after first study intervention administration) and at Day 29 and Day 113/197 (28 days after each study intervention administration) compared to Day 1 and Day 85/Day 169 (baseline))
- Number of adults 18 to 50 years of age in Africa showing at least a 4-fold increase in anti-serotype specific Shigella LPS/OAg serum IgG concentrations, as measured by GVGH ELISA(At Day 29 and Day 113 (28 days after each study intervention administration) compared to Day 1 and Day 85 (baseline))
- Number of infants 9 months of age in Africa showing at least a 4-fold increase in anti-serotype specific Shigella LPS/OAg serum IgG concentrations, as measured by GVGH ELISA(At Day 29, Day 113 and Day 281 (28 days after each study intervention administration) compared to Day 1, Day 85 and Day 253 (baseline))
- Anti-measles IgG concentrations in infants 9 months of age in the dose-finding groups in Africa(At Day 1 (before the first MR-VAC dose administration) and Day 281 (28 days after the second MR-VAC dose administration))
- Anti-rubella IgG concentrations in infants 9 months of age in the dose-finding groups in Africa(At Day 1 (before the first MR-VAC dose administration) and Day 281 (28 days after the second MR-VAC dose administration))
- Number of infants 9 months of age in the dose-finding groups in Africa achieving anti-measles IgG concentrations of ≥150 mIU/mL and ≥200 mIU/mL(At Day 281 (28 days after the second MR-VAC dose administration))
- Number of infants 9 months of age in the dose-finding groups in Africa achieving anti-rubella IgG concentrations of ≥4 IU/mL and ≥10 IU/mL(At Day 281 (28 days after the second MR-VAC dose administration))