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)
Overview
- Phase
- Phase 1
- Intervention
- altSonflex Placebo
- Conditions
- Diarrhoea
- Sponsor
- GlaxoSmithKline
- Enrollment
- 551
- Locations
- 1
- Primary Endpoint
- Number of adults 18 to 50 years of age in Europe with solicited administration site events
- Status
- Completed
- Last Updated
- 4 months ago
Overview
Brief Summary
The aim of the current clinical study is 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 will be first administered in adults 18 to 50 years of age in Europe. Subsequently, the vaccine will be administered to a shigellosis-endemic population in Africa, first in adults 18 to 50 years of age, then in children 24 to 59 months of age, finally in infants 9 months of age. Infants will also receive a third vaccination. Three different doses of the vaccine [low (Dose A), medium (Dose B), and high (Dose C) amounts of antigen] will be evaluated using an age de-escalation approach (from least vulnerable adult population to most vulnerable paediatric population). The results of this study will allow the selection of the most appropriate dose for further vaccine development in infants 9 months of age, which is the main target age group for this vaccine.
Investigators
Eligibility Criteria
Inclusion Criteria
- •All participants:
- •Participants and/or participants' parent(s)/legally acceptable representative(s) LAR(s), who, in the opinion of the investigator, can and will 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 obtained from the participant/parent(s)/LAR(s) of the participant prior to performance of any study specific procedure.
- •Healthy participants as established by medical history, clinical examination, and laboratory assessment.
- •Participants satisfying all screening requirements.
- •Participants seronegative for hepatitis B, and hepatitis C.
- •Participants 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.
Exclusion Criteria
- •All participants:
- •Known exposure to Shigella during 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 is applicable only to Adults 18 to 50 years of age in Europe (Stage 1).
- •Progressive, unstable or uncontrolled clinical conditions.
- •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 required).
- •Hypersensitivity, including allergy, to medicinal products or medical equipment whose use is 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, may interfere 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\*.
Arms & Interventions
ST1_Adults_Placebo_GR1 Group
Adults 18 to 50 years of age in Stage 1 (Europe) randomized to receive two doses of altSonflex Placebo, one each at Day 1 and Day 85.
Intervention: altSonflex Placebo
ST1_Adults_Dose C_GR1 Group
Adults 18 to 50 years of age in Stage 1 (Europe) randomized to receive two doses of altSonflex1-2-3 Dose C vaccine, one each at Day 1 and Day 85.
Intervention: altSonflex1-2-3 Dose C
ST1_Adults_Placebo_GR2 Group
Adults 18 to 50 years of age in Stage 1 (Europe) randomized to receive two doses of altSonflex Placebo, one each at Day 1 and Day 169.
Intervention: altSonflex Placebo
ST1_Adults_Dose C_GR2 Group
Adults 18 to 50 years of age in Stage 1 (Europe) randomized to receive two doses of altSonflex1-2-3 Dose C vaccine, one each at Day 1 and Day 169.
Intervention: altSonflex1-2-3 Dose C
ST2_Adults_Control C Group
Adults 18 to 50 years of age in Stage 2 (Africa) randomized to receive one dose of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine at Day 1 and one dose of GSK's Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine at Day 85.
Intervention: GSK's Meningococcal A, C, Y and W-135 conjugate vaccine
ST2_Adults_Control C Group
Adults 18 to 50 years of age in Stage 2 (Africa) randomized to receive one dose of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine at Day 1 and one dose of GSK's Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine at Day 85.
Intervention: GSK's Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine
ST2_Adults_Dose C Group
Adults 18 to 50 years of age in Stage 2 (Africa) randomized to receive two doses of altSonflex1-2-3 Dose C vaccine, one each at Day 1 and Day 85.
Intervention: altSonflex1-2-3 Dose C
ST2_Children_Control B Group
Children 24 to 59 months of age in Stage 2 (Africa) randomized to receive one dose of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine at Day 1 and one dose of Sanofi Pasteur's Typhoid Vi polysaccharide vaccine at Day 85. This group is a control group for children receiving altSonflex1-2-3 Dose B vaccine.
Intervention: GSK's Meningococcal A, C, Y and W-135 conjugate vaccine
ST2_Children_Control B Group
Children 24 to 59 months of age in Stage 2 (Africa) randomized to receive one dose of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine at Day 1 and one dose of Sanofi Pasteur's Typhoid Vi polysaccharide vaccine at Day 85. This group is a control group for children receiving altSonflex1-2-3 Dose B vaccine.
Intervention: Sanofi Pasteur's Typhoid Vi polysaccharide vaccine
ST2_Children_Dose B Group
Children 24 to 59 months of age in Stage 2 (Africa) randomized to receive two doses of altSonflex1-2-3 Dose B vaccine, one each at Day 1 and Day 85.
Intervention: altSonflex1-2-3 Dose B
ST2_Children_Control C Group
Children 24 to 59 months of age in Stage 2 (Africa) randomized to receive one dose of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine at Day 1 and one dose of Sanofi Pasteur's Typhoid Vi polysaccharide vaccine at Day 85. This group is a control group for children receiving altSonflex1-2-3 Dose C vaccine.
Intervention: GSK's Meningococcal A, C, Y and W-135 conjugate vaccine
ST2_Children_Control C Group
Children 24 to 59 months of age in Stage 2 (Africa) randomized to receive one dose of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine at Day 1 and one dose of Sanofi Pasteur's Typhoid Vi polysaccharide vaccine at Day 85. This group is a control group for children receiving altSonflex1-2-3 Dose C vaccine.
Intervention: Sanofi Pasteur's Typhoid Vi polysaccharide vaccine
ST2_Children_Dose C Group
Children 24 to 59 months of age in Stage 2 (Africa) randomized to receive two doses of altSonflex1-2-3 Dose C vaccine, one each at Day 1 and Day 85.
Intervention: altSonflex1-2-3 Dose C
ST2_Infants_Control A_Safety Group
Infants 9 months of age in Stage 2 (Africa), part of the safety cohort, randomized to receive two doses of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine, one each at Day 1 and Day 85, and one dose of GSK's Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis (inactivated), and Haemophilus influenzae type b vaccine at Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 29 and Day 281, as concomitant vaccination. This group is a control group for infants receiving altSonflex1-2-3 Dose A vaccine.
Intervention: GSK's Meningococcal A, C, Y and W-135 conjugate vaccine
ST2_Infants_Control A_Safety Group
Infants 9 months of age in Stage 2 (Africa), part of the safety cohort, randomized to receive two doses of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine, one each at Day 1 and Day 85, and one dose of GSK's Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis (inactivated), and Haemophilus influenzae type b vaccine at Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 29 and Day 281, as concomitant vaccination. This group is a control group for infants receiving altSonflex1-2-3 Dose A vaccine.
Intervention: GSK's Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis (inactivated), and Haemophilus influenzae type b vaccine
ST2_Infants_Control A_Safety Group
Infants 9 months of age in Stage 2 (Africa), part of the safety cohort, randomized to receive two doses of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine, one each at Day 1 and Day 85, and one dose of GSK's Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis (inactivated), and Haemophilus influenzae type b vaccine at Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 29 and Day 281, as concomitant vaccination. This group is a control group for infants receiving altSonflex1-2-3 Dose A vaccine.
Intervention: Serum Institute of India's Measles and rubella vaccine
ST2_Infants_Dose A_Safety Group
Infants 9 months of age in Stage 2 (Africa), part of the safety cohort, randomized to receive three doses of altSonflex1-2-3 Dose A, one each at Day 1, Day 85 and Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 29 and Day 281, as concomitant vaccination.
Intervention: altSonflex1-2-3 Dose A
ST2_Infants_Dose A_Safety Group
Infants 9 months of age in Stage 2 (Africa), part of the safety cohort, randomized to receive three doses of altSonflex1-2-3 Dose A, one each at Day 1, Day 85 and Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 29 and Day 281, as concomitant vaccination.
Intervention: Serum Institute of India's Measles and rubella vaccine
ST2_Infants_Control B_Safety Group
Infants 9 months of age in Stage 2 (Africa), part of the safety cohort, randomized to receive two doses of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine, one each at Day 1 and Day 85, and one dose of GSK's Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis (inactivated), and Haemophilus influenzae type b vaccine at Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 29 and Day 281, as concomitant vaccination. This group is a control group for infants receiving altSonflex1-2-3 Dose B vaccine.
Intervention: GSK's Meningococcal A, C, Y and W-135 conjugate vaccine
ST2_Infants_Control B_Safety Group
Infants 9 months of age in Stage 2 (Africa), part of the safety cohort, randomized to receive two doses of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine, one each at Day 1 and Day 85, and one dose of GSK's Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis (inactivated), and Haemophilus influenzae type b vaccine at Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 29 and Day 281, as concomitant vaccination. This group is a control group for infants receiving altSonflex1-2-3 Dose B vaccine.
Intervention: GSK's Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis (inactivated), and Haemophilus influenzae type b vaccine
ST2_Infants_Control B_Safety Group
Infants 9 months of age in Stage 2 (Africa), part of the safety cohort, randomized to receive two doses of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine, one each at Day 1 and Day 85, and one dose of GSK's Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis (inactivated), and Haemophilus influenzae type b vaccine at Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 29 and Day 281, as concomitant vaccination. This group is a control group for infants receiving altSonflex1-2-3 Dose B vaccine.
Intervention: Serum Institute of India's Measles and rubella vaccine
ST2_Infants_Dose B_Safety Group
Infants 9 months of age in Stage 2 (Africa), part of the safety cohort, randomized to receive three doses of altSonflex1-2-3 Dose B vaccine, one each at Day 1, Day 85 and Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 29 and Day 281, as concomitant vaccination.
Intervention: altSonflex1-2-3 Dose B
ST2_Infants_Dose B_Safety Group
Infants 9 months of age in Stage 2 (Africa), part of the safety cohort, randomized to receive three doses of altSonflex1-2-3 Dose B vaccine, one each at Day 1, Day 85 and Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 29 and Day 281, as concomitant vaccination.
Intervention: Serum Institute of India's Measles and rubella vaccine
ST2_Infants_Control C_Safety Group
Infants 9 months of age in Stage 2 (Africa), part of the safety cohort, randomized to receive two doses of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine, one each at Day 1 and Day 85, and one dose of GSK's Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis (inactivated), and Haemophilus influenzae type b vaccine at Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 29 and Day 281, as concomitant vaccination. This group is a control group for infants receiving altSonflex1-2-3 Dose C vaccine.
Intervention: GSK's Meningococcal A, C, Y and W-135 conjugate vaccine
ST2_Infants_Control C_Safety Group
Infants 9 months of age in Stage 2 (Africa), part of the safety cohort, randomized to receive two doses of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine, one each at Day 1 and Day 85, and one dose of GSK's Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis (inactivated), and Haemophilus influenzae type b vaccine at Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 29 and Day 281, as concomitant vaccination. This group is a control group for infants receiving altSonflex1-2-3 Dose C vaccine.
Intervention: GSK's Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis (inactivated), and Haemophilus influenzae type b vaccine
ST2_Infants_Control C_Safety Group
Infants 9 months of age in Stage 2 (Africa), part of the safety cohort, randomized to receive two doses of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine, one each at Day 1 and Day 85, and one dose of GSK's Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis (inactivated), and Haemophilus influenzae type b vaccine at Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 29 and Day 281, as concomitant vaccination. This group is a control group for infants receiving altSonflex1-2-3 Dose C vaccine.
Intervention: Serum Institute of India's Measles and rubella vaccine
ST2_Infants_Dose C_Safety Group
Infants 9 months of age in Stage 2 (Africa), part of the safety cohort, randomized to receive three doses of altSonflex1-2-3 Dose C vaccine, one each at Day 1, Day 85 and Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 29 and Day 281, as concomitant vaccination.
Intervention: altSonflex1-2-3 Dose C
ST2_Infants_Dose C_Safety Group
Infants 9 months of age in Stage 2 (Africa), part of the safety cohort, randomized to receive three doses of altSonflex1-2-3 Dose C vaccine, one each at Day 1, Day 85 and Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 29 and Day 281, as concomitant vaccination.
Intervention: Serum Institute of India's Measles and rubella vaccine
ST2_Infants_Control_Dose find Group
Infants 9 months of age in Stage 2 (Africa), part of the dose-finding cohort, randomized to receive two doses of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine, one each at Day 1 and Day 85, and one dose of GSK's Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis (inactivated), and Haemophilus influenzae type b vaccine at Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 1 and Day 253, as concomitant vaccination. This group is a control group for infants in dose-finding groups receiving either altSonflex1-2-3 Dose A, Dose B or Dose C vaccine.
Intervention: GSK's Meningococcal A, C, Y and W-135 conjugate vaccine
ST2_Infants_Control_Dose find Group
Infants 9 months of age in Stage 2 (Africa), part of the dose-finding cohort, randomized to receive two doses of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine, one each at Day 1 and Day 85, and one dose of GSK's Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis (inactivated), and Haemophilus influenzae type b vaccine at Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 1 and Day 253, as concomitant vaccination. This group is a control group for infants in dose-finding groups receiving either altSonflex1-2-3 Dose A, Dose B or Dose C vaccine.
Intervention: GSK's Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis (inactivated), and Haemophilus influenzae type b vaccine
ST2_Infants_Control_Dose find Group
Infants 9 months of age in Stage 2 (Africa), part of the dose-finding cohort, randomized to receive two doses of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine, one each at Day 1 and Day 85, and one dose of GSK's Diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis (inactivated), and Haemophilus influenzae type b vaccine at Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 1 and Day 253, as concomitant vaccination. This group is a control group for infants in dose-finding groups receiving either altSonflex1-2-3 Dose A, Dose B or Dose C vaccine.
Intervention: Serum Institute of India's Measles and rubella vaccine
ST2_Infants_Dose A_Dose find Group
Infants 9 months of age in Stage 2 (Africa), part of the dose-finding cohort, randomized to receive three doses of altSonflex1-2-3 Dose A vaccine, one each at Day 1, Day 85 and Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 1 and Day 253, as concomitant vaccination.
Intervention: altSonflex1-2-3 Dose A
ST2_Infants_Dose A_Dose find Group
Infants 9 months of age in Stage 2 (Africa), part of the dose-finding cohort, randomized to receive three doses of altSonflex1-2-3 Dose A vaccine, one each at Day 1, Day 85 and Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 1 and Day 253, as concomitant vaccination.
Intervention: Serum Institute of India's Measles and rubella vaccine
ST2_Infants_Dose B_Dose find Group
Infants 9 months of age in Stage 2 (Africa), part of the dose-finding cohort, randomized to receive three doses of altSonflex1-2-3 Dose B vaccine, one each at Day 1, Day 85 and Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 1 and Day 253, as concomitant vaccination.
Intervention: altSonflex1-2-3 Dose B
ST2_Infants_Dose B_Dose find Group
Infants 9 months of age in Stage 2 (Africa), part of the dose-finding cohort, randomized to receive three doses of altSonflex1-2-3 Dose B vaccine, one each at Day 1, Day 85 and Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 1 and Day 253, as concomitant vaccination.
Intervention: Serum Institute of India's Measles and rubella vaccine
ST2_Infants_Dose C_Dose find Group
Infants 9 months of age in Stage 2 (Africa), part of the dose-finding cohort, randomized to receive three doses of altSonflex1-2-3 Dose C vaccine, one each at Day 1, Day 85 and Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 1 and Day 253, as concomitant vaccination.
Intervention: altSonflex1-2-3 Dose C
ST2_Infants_Dose C_Dose find Group
Infants 9 months of age in Stage 2 (Africa), part of the dose-finding cohort, randomized to receive three doses of altSonflex1-2-3 Dose C vaccine, one each at Day 1, Day 85 and Day 253. These infants also receive two doses of Serum Institute of India's Measles and rubella vaccine, one each at Day 1 and Day 253, as concomitant vaccination.
Intervention: Serum Institute of India's Measles and rubella vaccine
Outcomes
Primary Outcomes
Number of adults 18 to 50 years of age in Europe with solicited administration site events
Time Frame: 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)
Time Frame: 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)
Time Frame: 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
Time Frame: 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
Time Frame: 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)
Time Frame: 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
Time Frame: 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)
Time Frame: 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
Time Frame: 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
Time Frame: 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)
Time Frame: 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)
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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)
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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
Time Frame: 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)
Time Frame: 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)
Time Frame: 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
Time Frame: 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)
Time Frame: 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)
Time Frame: 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.
Secondary Outcomes
- 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))