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

NCT05073003 | Completed Phase 1 Results

• 2 other identifiers: 2121492021-000891-12
• Study Type: interventional
• Target: 551
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Diarrhoea

Keywords

Shigella infection; Shigellosis; Diarrhoea; S. sonnei; S. flexneri; Low and middle income countries

Outcome Measures

Primary Outcomes (33)

• 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 Outcomes (24)

• Stage 1: Anti-serotype Specific Shigella LPS/OAg Serum IgG GMCs in Participants 18 to 50 Years of Age in Europe

  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)

Study Arms (16)

Stage 1 Adults: altSonflex1-2-3 High Dose Group 1

EXPERIMENTAL

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

Stage 1 Adults: altSonflex1-2-3 High Dose Group 2

EXPERIMENTAL

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

Stage 1 Adults: Placebo Group

PLACEBO COMPARATOR

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

Stage 2 Adults: altSonflex1-2-3 High Dose

EXPERIMENTAL

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

Stage 2 Adults: Control

ACTIVE COMPARATOR

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; Combination Product: Boostrix

Stage 2 Children: altSonflex1-2-3 Medium Dose

EXPERIMENTAL

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

Stage 2 Children: altSonflex1-2-3 High Dose

EXPERIMENTAL

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

Stage 2 Children: Control

ACTIVE COMPARATOR

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; Combination Product: Typhim-Vi

Stage 2 Infants safety cohort: altSonflex1-2-3 Low Dose

EXPERIMENTAL

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; Biological: MR-Vac

Stage 2 Infants safety cohort: altSonflex1-2-3 Medium Dose

EXPERIMENTAL

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; Biological: MR-Vac

Stage 2 Infants safety cohort: altSonflex1-2-3 High Dose

EXPERIMENTAL

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; Biological: MR-Vac

Stage 2 Infants safety cohort: Control

ACTIVE COMPARATOR

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; Combination Product: INFANRIX HEXA; Biological: MR-Vac

Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose

EXPERIMENTAL

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; Biological: MR-Vac

Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Medium Dose

EXPERIMENTAL

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; Biological: MR-Vac

Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose

EXPERIMENTAL

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; Biological: MR-Vac

Stage 2 Infants dose-finding cohort: Control

ACTIVE COMPARATOR

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; Combination Product: INFANRIX HEXA; Biological: MR-Vac

Interventions

altSonflex Placebo DRUG

2 doses in adults 18-50 years of age (stage 1)

Stage 1 Adults: Placebo Group

AltSonflex1-2-3 High Dose BIOLOGICAL

2 doses in adults 18-50 years of age and children 24-59 months of age, 3 doses in infants 9 months of age

Stage 1 Adults: altSonflex1-2-3 High Dose Group 1; Stage 1 Adults: altSonflex1-2-3 High Dose Group 2; Stage 2 Adults: altSonflex1-2-3 High Dose; Stage 2 Children: altSonflex1-2-3 High Dose; Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose; Stage 2 Infants safety cohort: altSonflex1-2-3 High Dose

AltSonflex1-2-3 Medium Dose BIOLOGICAL

2 doses in children 24-59 months of age, 3 doses in infants 9 months of age

Stage 2 Children: altSonflex1-2-3 Medium Dose; Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Medium Dose; Stage 2 Infants safety cohort: altSonflex1-2-3 Medium Dose

AltSonflex1-2-3 Low Dose BIOLOGICAL

3 doses in infants 9 months of age

Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose; Stage 2 Infants safety cohort: altSonflex1-2-3 Low Dose

Menveo BIOLOGICAL

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

Stage 2 Adults: Control; Stage 2 Children: Control; Stage 2 Infants dose-finding cohort: Control; Stage 2 Infants safety cohort: Control

Boostrix COMBINATION_PRODUCT

1 dose in adults 18-50 years of age (stage 2)

Stage 2 Adults: Control

INFANRIX HEXA COMBINATION_PRODUCT

1 dose in infants 9 months of age

Stage 2 Infants dose-finding cohort: Control; Stage 2 Infants safety cohort: Control

Typhim-Vi COMBINATION_PRODUCT

1 dose in children 24-59 months of age

Stage 2 Children: Control

MR-Vac BIOLOGICAL

2 doses in children 24-59 months of age

Stage 2 Infants dose-finding cohort: Control; Stage 2 Infants dose-finding cohort: altSonflex1-2-3 High Dose; Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Low Dose; Stage 2 Infants dose-finding cohort: altSonflex1-2-3 Medium Dose; Stage 2 Infants safety cohort: Control; Stage 2 Infants safety cohort: altSonflex1-2-3 High Dose; Stage 2 Infants safety cohort: altSonflex1-2-3 Low Dose; Stage 2 Infants safety cohort: altSonflex1-2-3 Medium Dose

Eligibility Criteria

• Age: 9 Months - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Ghent, 9000, Belgium

Location

GSK Investigational Site

Kericho, 20200, Kenya

Location

Related Publications (1)

• 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.

  PMID: 38853614 DERIVED

MeSH Terms

Conditions

Diarrhea; Dysentery, Bacillary

Interventions

Meningococcal Vaccines; Boostrix; diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine; Vi polysaccharide vaccine, typhoid

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Dysentery; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Observer blind
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2021
• First Posted: October 11, 2021
• Study Start: October 6, 2021
• Primary Completion: June 24, 2025
• Study Completion: June 24, 2025
• Last Updated: June 22, 2026
• Results First Posted: June 22, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

KE (1); BE (1)