NCT05073003 - A Study on the Safety and Immune Responses to the GVGH altSonflex1-2-3 Vaccine Against Shigellosis in Adults, Children, and Infants | Crick

Eligibility

Sex: ALLMin age: 9 MonthsMax age: 50 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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)

Time frame: 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)

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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)

Time frame: 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)

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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.

Time frame: At Day 8

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.

Time frame: 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.

Time frame: 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.

Time frame: At Day 260

Secondary Outcomes

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.

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

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

Overview

Conditions

Interventions

Eligibility

Locations (2)

Outcomes

Primary Outcomes

Secondary Outcomes