Diarrhoea
Conditions
Keywords
Shigella, Shigellosis, altSonflex1-2-3, Infants, African, Safety, Immunogenicity
Brief summary
This study evaluates the immune response and safety of a multicomponent, 2-dose Shigella vaccine in preventing shigellosis in African infants. The candidate vaccine, altSonflex1-2-3, is currently being evaluated in a Phase 2 age de-escalation (from least vulnerable adult population to most vulnerable paediatric population) clinical study in Kenya, with the aim of identifying a preferred dose, using a 3-dose vaccination schedule in infants from 9 months of age (NCT05073003). This Phase 2 clinical study will evaluate the safety and immunogenicity of an alternative 2-dose vaccination schedule.
Interventions
BIOLOGICALaltSonflex1-2-3 Dose A
altSonflex1-2-3 Dose A administered intramuscularly on Day 1 and Day 169
BIOLOGICALaltSonflex1-2-3 Dose B
altSonflex1-2-3 Dose B administered intramuscularly on Day 1 and Day 169
BIOLOGICALaltSonflex1-2-3 Dose C
altSonflex1-2-3 Dose C administered intramuscularly on Day 1 and Day 169
BIOLOGICALTYPHIBEV
TYPHIBEV administered intramuscularly on Day 1
COMBINATION_PRODUCTInfanrix hexa
Infanrix hexa administered intramuscularly on Day 169
BIOLOGICALMR-VAC
MR-VAC co-administered subcutaneously on Day 1 and Day 169
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
39 Weeks to 43 Weeks
Healthy volunteers
Yes
Inclusion criteria
* Participants' parent(s)/ Legally acceptable representative (LAR), who, in the opinion of the investigator, can and will comply with the requirements of the protocol. * Written or witnessed/thumb printed informed consent obtained from the parent(s)/LAR(s) of the participant prior to performance of any study specific procedure. * Healthy participants as established by medical history, clinical examination, and laboratory assessment. * Participants satisfying all screening requirements. * Participants seronegative for hepatitis B, and hepatitis C. * A male or female 9 months of age at the time of the first study intervention administration. * Normal nutritional z-score. * Previously completed routine childhood vaccinations to the best knowledge of the participant's parent(s)/LAR(s). * Born at a gestation period of \>=37 weeks to the best knowledge of the participant's parent(s)/LAR(s). * Participants negative for human immunodeficiency virus as confirmed by DNA polymerase chain reaction testing. * Participants negative for HLA-B27.
Exclusion criteria
* Known exposure to Shigella during lifetime of the participant as confirmed during interview with the participant's parent(s)/LAR(s) or documented by participant's records. * Progressive, unstable, or uncontrolled clinical conditions. * History (known or suspected) of any reaction or hypersensitivity likely to be exacerbated by any component of the study intervention. * Major congenital defects, as assessed by the investigator. * Recurrent history or uncontrolled neurological disorders or seizures. * Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. * Hypersensitivity (known or suspected), including allergy, to medicinal products, vaccines, or medical equipment whose use is foreseen in this study. * Clinical conditions representing a contraindication to intramuscular vaccination and blood draws. * Any behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the participant's ability to participate in the study. * Acute disease and/or fever (defined as temperature \>=38.0°C) at the time of enrollment. * Any clinically significant hematological and/or biochemical laboratory abnormality. * Confirmed positive COVID-19 test during the period starting 30 days before the first administration of study interventions (Day -30 to Day 1). * Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant due to participation in the study. * Acute or chronic clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by physical examination or laboratory screening tests. * Use of any investigational or non-registered product (drug, vaccine or invasive medical device) other than the study intervention(s) during the period beginning 30 days before the first dose of study intervention(s) (Day -30 to Day 1), or their planned use during the study period. * Planned administration/administration of a vaccine/product not foreseen by the Protocol in the period starting 21 days before the first dose and ending after the last dose of study intervention(s) administration with the exception of Coronavirus disease 2019 (COVID-19) vaccines and Expanded Program on Immunization (EPI) vaccines. * Administration of long-acting immune-modifying drugs at any time during the study period. * Prior receipt of an experimental Shigella vaccine or live Shigella challenge. * Prior receipt of a Typhoid conjugate vaccine (TCV). * Administration of immunoglobulins and/or any blood products or plasma derivatives, or bone marrow transplantation, from birth or planned administration during the study period. * Chronic administration of immune-modifying drugs (defined as more than 14 days consecutive days in total) and/or planned use of long-acting immune-modifying treatments at any time up to the end of the study. * Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention drug or invasive medical device. * Any study personnel or immediate dependents, family, or household member. * Child in care. * Participants who do not meet eligibility criteria for administration of control vaccines.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With at Least a 4-fold Increase in Anti-serotype Specific Shigella LPS/OAg Serum IgG | At Day 29 compared to baseline (before administration of Dose 1 on Day 1) | S. sonnei, S. flexneri 1b, S. flexneri 2a, and S. flexneri 3a serotypes were tested. |
| Geometric Mean Concentrations (GMCs) of Anti-serotype Specific Shigella Lipopolysaccharide (LPS)/O-Antigen (OAg) Serum Immunoglobulin G (IgG) | At Day 1 (before administration of Dose 1) | 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. S. sonnei, S. flexneri 1b, S. flexneri 2a, and S. flexneri 3a serotypes were tested. |
| GMCs of Anti-serotype Specific Shigella LPS/OAg Serum IgG | At Day 29 (28 days after administration of Dose 1) | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Anti-measles IgG Concentrations Expressed as GMCs | At Day 1 (before the first MR-VAC) and at Day 197 (28 days after the second MR-VAC vaccination) | Anti-measles IgG concentrations were expressed as GMCs in EU/mL. |
| Anti-rubella IgG Concentrations Expressed as GMCs | At Day 1 (before the first MR-VAC) and at Day 197 (28 days after the second MR-VAC vaccination) | Anti-rubella IgG concentrations were expressed as GMCs in EU/mL. |
| Number of Participants Achieving Anti-measles IgG Concentrations of ≥150 Milli International Units Per Milliliter (mIU/mL) and ≥200 mIU/mL | At Day 197 (28 days after the second MR-VAC vaccination) | — |
| Number of Participants Achieving Anti-rubella IgG Concentrations of ≥4 IU/mL and ≥10 IU/mL | At Day 197 (28 days after the second MR-VAC vaccination) | — |
| Number of Participants With Solicited Administration Site Events | During the 7 days after each study intervention administration (study intervention administered at Day 1 and Day 169) | The solicited administration site events assessed were erythema, pain and swelling. |
| Number of Participants With Solicited Systemic Events | During the 7 days after each study intervention administration (study interventions administered at Day 1 and Day 169) | The solicited systemic event assessed was fever (pyrexia). Fever is defined as temperature ≥38.0°Celsius (C), measured axillary. |
| Number of Participants With Unsolicited Adverse Events (AEs) | During the 28 days after each study intervention administration (study interventions administered at Day 1 and Day 169) | An unsolicited AE is an AE that was either not included in the list of solicited events or could be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events. |
| Number of Participants With Serious AEs (SAEs) | Day 1 to Day 197 | An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study participant, results in abnormal pregnancy outcomes or any other situation based on appropriate medical or scientific judgement. |
| Number of Participants With Change From Baseline in Hematological, Renal, and Hepatic Panel Test Results With Respect to Laboratory Reference Ranges at Day 176 | Day 176 compared to pre-Dose 2 at Day 169 | Panel tests include measures of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, potassium, sodium, blood urea, basophils, eosinophils, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Categories reported when comparing Day 169 (baseline) and laboratory reference 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. |
| Number of Participants With Change From Baseline in Hematological, Renal, and Hepatic Panel Test Results With Respect to Laboratory Reference Ranges at Day 8 | Day 8 compared to baseline (pre-Dose 1 at Day 1) | Panel tests include measures of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, potassium, sodium, blood urea, basophils, eosinophils, erythrocytes, hematocrit, hemoglobin, leukocytes, lymphocytes, monocytes, neutrophils and platelets. Categories reported when comparing Day 1 (baseline) and laboratory reference 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. |
| The Number of Participants With Abnormal Hematological, Renal, and Hepatic Panel Test Results by Grade Values at Day 8 Versus Baseline (Day 1) Grade Values | Day 8 compared to baseline (before administration of Dose 1 at Day 1) | Panel tests include measures of ALT, AST, creatinine, hemoglobin, neutrophils decrease, platelets decrease and white blood cells (WBC) decrease. Categories reported when comparing Day 1 (baseline) and laboratory reference range hematological, renal and hepatic laboratory results are defined as follows: \<parameter\>,\<grade at baseline\>,\<grade at timing\>, where Grade 0=within reference range, Grade 1= mild, Grade 2=moderate, Grade 3=severe and Grade 4=potentially life threatening laboratory abnormality. |
| The Number of Participants With Abnormal Hematological, Renal, and Hepatic Panel Test Results by Grade Values at Day 176 Versus Day 169 Grade Values | Day 176 compared to pre-Dose 2 at Day 169 | Panel tests include measures of ALT, AST, creatinine, hemoglobin, neutrophils decrease, platelets decrease and white blood cells (WBC) decrease. Categories reported when comparing Day 169 and laboratory reference range hematological, renal and hepatic laboratory results are defined as follows: \<parameter\>,\<grade at baseline\>,\<grade at timing\>, where Grade 0=within reference range, Grade 1= mild, Grade 2=moderate, Grade 3=severe and Grade 4=potentially life threatening laboratory abnormality. |
Countries
Kenya
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 9.3 Months STANDARD_DEVIATION 0.5 |
| Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN | 50 Participants |
| Sex: Female, Male Female | 35 Participants |
| Sex: Female, Male Male | 88 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 50 | 0 / 50 | 0 / 50 |
| other Total, other adverse events | 41 / 50 | 35 / 50 | 42 / 50 | 40 / 50 |
| serious Total, serious adverse events | 1 / 50 | 0 / 50 | 0 / 50 | 0 / 50 |
Outcome results
None listed