A Study on the Safety and Immune Responses to the GVGH altSonflex1-2-3 Vaccine Against Shigellosis in Adults, Children, and Infants

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)

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.

Study Overview

• Status: Completed
• Conditions: Diarrhoea
• Intervention / Treatment: Biological: AltSonflex1-2-3 High Dose; Drug: altSonflex Placebo; Biological: Menveo; Combination product: Boostrix; Biological: AltSonflex1-2-3 Medium Dose; Combination product: Typhim-Vi; Biological: AltSonflex1-2-3 Low Dose; Biological: MR-Vac; Combination product: INFANRIX HEXA

• Study Type: Interventional
• Enrollment (Actual): 551
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Ghent, Belgium, 9000
    • GSK Investigational Site
• Kenya
  • Kericho, Kenya, 20200
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 months to 50 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Quadruple

Number of Arms

16

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Biological: AltSonflex1-2-3 High Dose; 2 doses in adults 18-50 years of age and children 24-59 months of age, 3 doses in infants 9 months of age
Experimental: 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).	Biological: AltSonflex1-2-3 High Dose; 2 doses in adults 18-50 years of age and children 24-59 months of age, 3 doses in infants 9 months of age
Placebo Comparator: 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.	Drug: altSonflex Placebo; 2 doses in adults 18-50 years of age (stage 1)
Experimental: 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).	Biological: AltSonflex1-2-3 High Dose; 2 doses in adults 18-50 years of age and children 24-59 months of age, 3 doses in infants 9 months of age
Active Comparator: 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.	Biological: Menveo; 1 dose in adults 18-50 years of age (stage 2) and children 24-59 months of age and 2 doses in infants 9 months of age; Combination product: Boostrix; 1 dose in adults 18-50 years of age (stage 2)
Experimental: 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).	Biological: AltSonflex1-2-3 Medium Dose; 2 doses in children 24-59 months of age, 3 doses in infants 9 months of age
Experimental: 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).	Biological: AltSonflex1-2-3 High Dose; 2 doses in adults 18-50 years of age and children 24-59 months of age, 3 doses in infants 9 months of age
Active Comparator: 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.	Biological: Menveo; 1 dose in adults 18-50 years of age (stage 2) and children 24-59 months of age and 2 doses in infants 9 months of age; Combination product: Typhim-Vi; 1 dose in children 24-59 months of age
Experimental: 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).	Biological: AltSonflex1-2-3 Low Dose; 3 doses in infants 9 months of age; Biological: MR-Vac; 2 doses in children 24-59 months of age
Experimental: 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).	Biological: AltSonflex1-2-3 Medium Dose; 2 doses in children 24-59 months of age, 3 doses in infants 9 months of age; Biological: MR-Vac; 2 doses in children 24-59 months of age
Experimental: 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).	Biological: AltSonflex1-2-3 High Dose; 2 doses in adults 18-50 years of age and children 24-59 months of age, 3 doses in infants 9 months of age; Biological: MR-Vac; 2 doses in children 24-59 months of age
Active Comparator: 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.	Biological: Menveo; 1 dose in adults 18-50 years of age (stage 2) and children 24-59 months of age and 2 doses in infants 9 months of age; Biological: MR-Vac; 2 doses in children 24-59 months of age; Combination product: INFANRIX HEXA; 1 dose in infants 9 months of age
Experimental: 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).	Biological: AltSonflex1-2-3 Low Dose; 3 doses in infants 9 months of age; Biological: MR-Vac; 2 doses in children 24-59 months of age
Experimental: 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).	Biological: AltSonflex1-2-3 Medium Dose; 2 doses in children 24-59 months of age, 3 doses in infants 9 months of age; Biological: MR-Vac; 2 doses in children 24-59 months of age
Experimental: 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).	Biological: AltSonflex1-2-3 High Dose; 2 doses in adults 18-50 years of age and children 24-59 months of age, 3 doses in infants 9 months of age; Biological: MR-Vac; 2 doses in children 24-59 months of age
Active Comparator: 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.	Biological: Menveo; 1 dose in adults 18-50 years of age (stage 2) and children 24-59 months of age and 2 doses in infants 9 months of age; Biological: MR-Vac; 2 doses in children 24-59 months of age; Combination product: INFANRIX HEXA; 1 dose in infants 9 months of age

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage 2: Geometric Mean Concentrations (GMCs) of Anti-serotype Specific Shigella Lipopolysaccharide (LPS)/O-Antigen (OAg) Serum Immunoglobulin G (IgG) in Participants 9 Months of Age in Africa	Anti-serotype specific Shigella LPS/OAg serum IgG GMCs were measured by enzyme-linked immunosorbent assay (ELISA) and expressed in ELISA units per milliliter (EU/mL) of serum. Four serotypes were tested. Due to the fact, that the Per protocol set (PPS) for Stage 2 Infants - dose finding cohort had less than the 72 participants per group defined in the protocol as a minimum number of participants to ensure power of the analysis, the Stage 2 Infants Safety cohort and Dose-finding cohort were pooled for the statistical analysis as per the Statistical Analysis Plan. As per protocol, statistical analysis was performed only for the S. sonnei serotype, comparing Stage 2 Infants: Pooled groups (medium vs low dose); and Stage 2 Infants Dose-finding groups (high vs low dose). The objective of this outcome measure is to identify the preferred dose of each component of the altSonflex1-2-3 vaccine for infants 9 months of age in Africa, therefore control groups were not analyzed.	At Day 281 (28 days after the third study intervention)
Stage 1: Number of Participants 18 to 50 Years of Age in Europe With Solicited Administration Site Events	The solicited administration site events assessed were erythema, pain, and swelling.	Within 7 days after each study intervention (administered at Day 1, Day 85 and Day 169 [depending on the vaccination schedule])
Stage 1: Number of Adults 18 to 50 Years of Age in Europe With Solicited Systemic Events	The solicited systemic event assessed was fever. Fever is defined as temperature equal to or above (=>) 38.0°C.	Within 7 days after each study intervention (administered at Day 1, Day 85 and Day 169 [depending on the vaccination schedule])
Stage 1: Number of Participants 18 to 50 Years of Age in Europe With Unsolicited Adverse Events (AEs)	An unsolicited AE is defined as 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.	Within 28 days after each study intervention (administered at at Day 1, Day 85 and Day 169 [depending on the vaccination schedule])
Stage 1: Number of Participants 18 to 50 Years of Age in Europe With Serious Adverse Events (SAEs)	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.	From Day 1 to Day 113 and/or Day 197
Stage 1: Number of Participants 18 to 50 Years of Age in Europe With Deviations From Normal Values of Haematological, Renal, and Hepatic Panel Test Results After First Study Intervention	Panel tests include measures of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBC). Categories reported when comparing Day 1 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.	At Day 8
Stage 1: Number of Participants 18 to 50 Years of Age in Europe With Deviations From Normal Values of Haematological, Renal, and Hepatic Panel Test Results After Second Study Intervention	Panel tests include measures of ALT, AST, creatinine, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and WBC. Categories reported when comparing Day 85/Day 169 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.	At Day 92 (Stage 1 Adults: altSonflex1-2-3 High Dose Group 1), at Day 176 (Stage 1 Adults: altSonflex1-2-3 High Dose Group 2) and at Day 92/Day 176 (Stage 1 Adults: Placebo Group)
Stage 2: Number of Participants 18 to 50 Years of Age in Africa With Solicited Administration Site Events	The solicited administration site events assessed were pain, erythema, and swelling.	Within 7 days after each study intervention (administered at Day 1 and Day 85)
Stage 2: Number of Participants 18 to 50 Years of Age in Africa With Solicited Systemic Events	The solicited systemic event assessed was fever. Fever is defined as temperature equal to or above (=>) 38.0°C.	Within 7 days after each study intervention (administered at Day 1 and Day 85)
Stage 2: Number of Participants 18 to 50 Years of Age in Africa With Unsolicited Adverse Events (AEs)	An unsolicited AE is defined as 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.	Within 28 days after each study intervention (administered at Day 1 and Day 85)
Stage 2: Number of Participants 18 to 50 Years of Age in Africa With Serious Adverse Events (SAEs)	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.	From Day 1 to Day 113
Stage 2: Number of Participants 18 to 50 Years of Age in Africa With Deviations From Normal Values of Haematological, Renal, and Hepatic Panel Test Results After First Study Intervention	Panel tests include measures of ALT, AST, creatinine, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and WBC. Categories reported when comparing Day 1 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.	At Day 8
Stage 2: Number of Participants 18 to 50 Years of Age in Africa With Deviations From Normal Values of Haematological, Renal, and Hepatic Panel Test Results After Second Study Intervention	Panel tests include measures of ALT, AST, creatinine, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and WBC. Categories reported when comparing Day 85 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.	At Day 92
Stage 2: Number of Participants 24 to 59 Months of Age in Africa With Solicited Administration Site Events	The solicited administration site events assessed were erythema, pain, and swelling.	Within 7 days after each study intervention (administered at Day 1 and Day 85)
Stage 2: Number of Participants 24 to 59 Months of Age in Africa With Solicited Systemic Events	The solicited systemic event assessed was fever. Fever is defined as temperature equal to or above (=>) 38.0°C.	Within 7 days after each study intervention (administered at Day 1 and Day 85)
Stage 2: Number of Participants 24 to 59 Months of Age in Africa With Unsolicited Adverse Events (AEs)	An unsolicited AE is defined as 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.	Within 28 days after each study intervention (administered at Day 1 and Day 85)
Stage 2: Number of Participants 24 to 59 Months of Age in Africa With Serious Adverse Events (SAEs)	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.	From Day 1 to Day 113
Stage 2: Number of Participants 24 to 59 Months of Age in Africa With Deviations From Normal Values of Haematological, Renal, and Hepatic Panel Test Results After First Study Intervention	Panel tests include measures of ALT, AST, creatinine, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and WBC. Categories reported when comparing Day 1 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.	At Day 8
Stage 2: Number of Participants 24 to 59 Months of Age in Africa With Deviations From Normal Values of Haematological, Renal, and Hepatic Panel Test Results After Second Study Intervention	Panel tests include measures of ALT, AST, creatinine, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and WBC. Categories reported when comparing Day 85 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.	At Day 92
Stage 2: Number of Participants 9 Months of Age in Africa With Solicited Administration Site Events - Infants Safety Cohort	The solicited administration site events assessed were erythema, pain, and swelling.	Within 7 days after each study intervention (administered at Day 1, Day 85 and Day 253)
Stage 2: Number of Participants 9 Months of Age in Africa With Solicited Administration Site Events - Infants Dose-finding Cohort	The solicited administration site events assessed were erythema, pain, and swelling.	Within 7 days after each study intervention (administered at Day 1, Day 85 and Day 253)
Stage 2: Number of Participants 9 Months of Age in Africa With Solicited Systemic Events - Infants Safety Cohort	The solicited systemic event is fever. Fever is defined as temperature equal to or above (=>) 38.0°C.	Within 7 days after each study intervention (administered at Day 1, Day 85 and Day 253)
Stage 2: Number of Participants 9 Months of Age in Africa With Solicited Systemic Events - Infants Dose-finding Cohort	The solicited systemic event is fever. Fever is defined as temperature equal to or above (=>) 38.0°C.	Within 7 days after each study intervention (administered at Day 1, Day 85 and Day 253)
Stage 2: Number of Participants 9 Months of Age in Africa With Unsolicited Adverse Events (AEs) - Infants Safety Cohort	An unsolicited AE is defined as 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.	Within 28 days after each study intervention (administered at Day 1, Day 85 and Day 253)
Stage 2: Number of Participants 9 Months of Age in Africa With Unsolicited Adverse Events (AEs) - Infants Dose-finding Cohort	An unsolicited AE is defined as 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.	Within 28 days after each study intervention (administered at Day 1, Day 85 and Day 253)
Stage 2: Number of Participants 9 Months of Age in Africa With Serious Adverse Events (SAEs) - Infants Safety Cohort	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.	From Day 1 to Day 281
Stage 2: Number of Participants 9 Months of Age in Africa With Serious Adverse Events (SAEs) - Infants Dose-finding Cohort	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.	From Day 1 to Day 281
Stage 2: Number of Participants 9 Months of Age in Africa With Deviations From Normal Values of Haematological, Renal, and Hepatic Panel Test Results After First Study Intervention - Infants Safety Cohort	Panel tests include measures of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, potassium, sodium, urea, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBC). Categories reported when comparing Day 1 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.	At Day 8
Stage 2: Number of Participants 9 Months of Age in Africa With Deviations From Normal Values of Haematological, Renal, and Hepatic Panel Test Results After First Study Intervention - Infants Dose-finding Cohort	Panel tests include measures of ALT, AST, creatinine, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and WBC. Categories reported when comparing Day 1 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.	At Day 8
Stage 2: Number of Participants 9 Months of Age in Africa With Deviations From Normal Values of Haematological, Renal, and Hepatic Panel Test Results After Second Study Intervention - Infants Safety Cohort	Panel tests include measures of ALT, AST, creatinine, potassium, sodium, urea, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and WBC. Categories reported when comparing Day 1 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.	At Day 92
Stage 2: Number of Participants 9 Months of Age in Africa With Deviations From Normal Values of Haematological, Renal, and Hepatic Panel Test Results After Second Study Intervention - Infants Dose-finding Cohort	Panel tests include measures of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, potassium, sodium, urea, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBC). Categories reported when comparing Day 1 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.	At Day 92
Stage 2: Number of Participants 9 Months of Age in Africa With Deviations From Normal Values of Haematological, Renal, and Hepatic Panel Test Results After Third Study Intervention - Infants Safety Cohort	Panel tests include measures of ALT, AST, creatinine, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and WBC. Categories reported when comparing Day 1 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.	At Day 260
Stage 2: Number of Participants 9 Months of Age in Africa With Deviations From Normal Values of Haematological, Renal, and Hepatic Panel Test Results After Third Study Intervention - Infants Dose-finding Cohort	Panel tests include measures of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, potassium, sodium, urea, basophils, eosinophils, erythrocytes, haematocrit, haemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBC). Categories reported when comparing Day 1 (baseline) and normal range hematological, renal and hepatic laboratory results are defined as follows: <parameter>,<range at baseline>,<range at timing>, where range is being classified as Below = value below; Within = value within; and Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.	At Day 260

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage 1: Anti-serotype Specific Shigella LPS/OAg Serum IgG GMCs in Participants 18 to 50 Years of Age in Europe	Anti-serotype specific Shigella LPS/OAg serum IgG GMCs were measured by ELISA and expressed in EU/mL of serum. S. sonnei, S. flexneri 1b, S. flexneri 2a, and S. flexneri 3a serotypes were tested.	At Day 1 and Day 85/Day 169(before each study intervention); at Day 15 (14 days after the first study intervention); at Day 29 and Day 113/Day 197 (28 days after each study intervention)
Stage 2: Anti-serotype Specific Shigella LPS/OAg Serum IgG GMCs in Participants 18 to 50 Years of Age in Africa		At Day 1 and Day 85 (before each study intervention administration) and Day 29 and Day 113 (28 days after each study intervention administration)
Stage 2: Anti-serotype Specific Shigella LPS/OAg Serum IgG GMCs in Participants 24 to 59 Months of Age in Africa		At Day 1 and Day 85 (before each study intervention) and Day 29 and Day 113 (28 days after each study intervention)
Stage 2: Anti-serotype Specific Shigella LPS/OAg Serum IgG GMCs in Participants 9 Months of Age in Africa - Infants Safety Cohort		At Day 1, Day 85 and Day 253 (before each study intervention administration) and Day 29, Day 113 and Day 281 (28 days after each study intervention administration)
Stage 2: Anti-serotype Specific Shigella LPS/OAg Serum IgG GMCs in Participants 9 Months of Age in Africa - Dose-finding Cohort		At Day 1, Day 85 and Day 253 (before each study intervention administration) and Day 29, Day 113 and Day 281 (28 days after each study intervention administration)
Stage 1: Number of Participants 18 to 50 Years of Age 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); at Day 15 (14 days after the first study intervention); at Day 29 and Day 113/Day 197 (28 days after each study intervention)
Stage 2: Number of Participants 18 to 50 Years of Age 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) and Day 29 and Day 113 (28 days after each study intervention)
Stage 2: Number of Participants 24 to 59 Months of Age 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) and Day 29 and Day 113 (28 days after each study intervention)
Stage 2: Number of Participants 9 Months of Age Achieving a GVGH ELISA Level Equivalent to ≥1:800 Titer Against S. Sonnei LPS/Oag - Safety Cohort		At Day 1, Day 85 and Day 253 (before each study intervention) and Day 29, Day 113 and Day 281 (28 days after each study intervention)
Stage 2: Number of Participants 9 Months of Age Achieving a GVGH ELISA Level Equivalent to ≥1:800 Titer Against S. Sonnei LPS/Oag - Dose-finding Cohort		At Day 1, Day 85 and Day 253 (before each study intervention) and Day 29, Day 113 and Day 281 (28 days after each study intervention)
Stage 1: Number of Participants 18 to 50 Years of Age 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); at Day 15 (14 days after the first study intervention); at Day 29 and Day 113/Day 197 (28 days after each study intervention)
Stage 2: Number of Participants 18 to 50 Years of Age 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) and Day 29 and Day 113 (28 days after each study intervention)
Stage 2: Number of Participants 24 to 59 Months of Age 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) and Day 29 and Day 113 (28 days after each study intervention)
Stage 2: Number of Participants 9 Months of Age Achieving a GVGH ELISA Level Equivalent to ≥1:1600 Titer Against S. Sonnei LPS/OAg - Safety Cohort		At Day 1, Day 85 and Day 253 (before each study intervention) and Day 29, Day 113 and Day 281 (28 days after each study intervention)
Stage 2: Number of Participants 9 Months of Age Achieving a GVGH ELISA Level Equivalent to ≥1:1600 Titer Against S. Sonnei LPS/OAg - Dose-finding Cohort		At Day 1, Day 85 and Day 253 (before each study intervention) and Day 29, Day 113 and Day 281 (28 days after each study intervention)
Stage 1: Number of Participants 18 to 50 Years of Age 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 the first study intervention) and at Day 29 and Day 113/Day 197 (28 days after each study intervention) compared to baseline (Day 1 and Day 85/Day 169)
Stage 2: Number of Participants 18 to 50 Years of Age 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) compared to baseline (Day 1 and Day 85)
Stage 2: Number of Participants 24 to 59 Months of Age 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) compared to baseline (Day 1 and Day 85)
Stage 2: Number of Participants 9 Months of Age Showing at Least a 4-fold Increase in Anti-serotype Specific Shigella LPS/OAg Serum IgG Concentrations, as Measured by GVGH ELISA - Safety Cohort		At Day 29, Day 113 and Day 281 (28 days after each study intervention) compared to baseline (Day 1, Day 85 and Day 253)
Stage 2: Number of Participants 9 Months of Age Showing at Least a 4-fold Increase in Anti-serotype Specific Shigella LPS/OAg Serum IgG Concentrations, as Measured by GVGH ELISA - Dose-finding Cohort		At Day 29, Day 113 and Day 281 (28 days after each study intervention) compared to baseline (Day 1, Day 85 and Day 253)
Stage 2: Anti-measles IgG Concentrations in Participants 9 Months of Age in the Dose-finding Cohort		At Day 1 (before first measles and rubella vaccine (MR-VAC)) and at Day 281 (28 days after the second MR-VAC administration)
Stage 2: Anti-rubella IgG Concentrations in Participants 9 Months of Age in the Dose-finding Groups		At Day 1 (before first measles and rubella vaccine (MR-VAC)) and at Day 281 (28 days after the second MR-VAC administration)
Stage 2: Number of Participants 9 Months of Age in the Dose-finding Groups Achieving Anti-measles IgG Concentrations of ≥150 Milli International Units Per Milliliter (mIU/mL) and ≥200 mIU/mL		Day 281 (28 days after the second MR-VAC administration)
Stage 2: Number of Participants 9 Months of Age in the Dose-finding Groups Achieving Anti-rubella IgG Concentrations of ≥4 mIU/mL and ≥10 mIU/mL		Day 281 (28 days after the second MR-VAC administration)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Publications and helpful links

General Publications

• Leroux-Roels I, Maes C, Mancini F, Jacobs B, Sarakinou E, Alhatemi A, Joye J, Grappi S, Cilio GL, Serry-Bangura A, Vitali CG, Ferruzzi P, Marchetti E, Necchi F, Rappuoli R, De Ryck I, Auerbach J, Colucci AM, Rossi O, Conti V, Scorza FB, Arora AK, Micoli F, Podda A, Nakakana UN; Shigella Project Team. Safety and Immunogenicity of a 4-Component Generalized Modules for Membrane Antigens Shigella Vaccine in Healthy European Adults: Randomized, Phase 1/2 Study. J Infect Dis. 2024 Oct 16;230(4):e971-e984. doi: 10.1093/infdis/jiae273.

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2021
• Primary Completion (Actual): June 24, 2025
• Study Completion (Actual): June 24, 2025

Study Registration Dates

• First Submitted: September 29, 2021
• First Submitted That Met QC Criteria: September 29, 2021
• First Posted (Actual): October 11, 2021

Study Record Updates

• Last Update Posted (Actual): June 22, 2026
• Last Update Submitted That Met QC Criteria: June 18, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Shigellosis; Diarrhoea; Low and middle income countries; S. sonnei; Shigella infection; S. flexneri
• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Intestinal Diseases; Infections; Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Enterobacteriaceae Infections; Dysentery; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Diarrhea; Dysentery, Bacillary; Biological Products; Complex Mixtures; Bacterial Vaccines; Vaccines; Meningococcal Vaccines; Boostrix; diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine; Vi polysaccharide vaccine, typhoid
• Other Study ID Numbers: 212149; 2021-000891-12 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: GSK will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No