A Study to Evaluate Safety, Reactogenicity, and Immune Response of GVGH iNTS-TCV Vaccine Against Invasive Nontyphoidal Salmonella and Typhoid Fever

NCT05480800 | Completed Phase 1 Results DMC

• 2 other identifiers: 2161522021-005178-25
• Study Type: interventional
• Target: 155
• Locations: 2 countries
• Sites: 2

Brief Summary

The purpose of this study is to assess the safety, reactogenicity, and immune response induced by the GlaxoSmithKline Biologicals SA (GSK) Vaccines Institute for Global Health (GVGH) invasive nontyphoidal Salmonella-typhoid conjugate (iNTS-TCV) candidate vaccine to be administered for the first time in humans. The study intervention will be evaluated in European adults in Stage 1 (a 2-step staggered design) followed by African adults in Stage 2.

Conditions

Salmonella Infections

Outcome Measures

Primary Outcomes (36)

• Stage 1: Number of Participants With Any Solicited Administration Site Events After the First Study Intervention Administration

  The solicited administration site events included redness (erythema), pain, and swelling. Data for solicited administration site events is presented for each intervention administered in each arm group. Any = occurrence of the event regardless of intensity grade.

  Within 7 days post vaccination (day of administration and 6 subsequent days post-first vaccination on Day 1)

• Stage 1: Number of Participants With Any Solicited Administration Site Events After the Second Study Intervention Administration

  The solicited administration site events included redness (Erythema), pain and swelling. Data for solicited administration site events is presented for each intervention administered in each arm group. Any = occurrence of the event regardless of intensity grade.

  Within 7 days post vaccination (day of administration and 6 subsequent days post-second vaccination on Day 57)

• Stage 1: Number of Participants With Any Solicited Administration Site Events After the Third Study Intervention Administration

  The solicited administration site events included redness (Erythema), pain and swelling. Data for solicited administration site events is presented for each intervention administered in each arm group. Any = occurrence of the event regardless of intensity grade.

  Within 7 days post vaccination (day of administration and 6 subsequent days post-third vaccination on Day 169)

• Stage 1: Number of Participants With Any Solicited Systemic Events After the First Study Intervention Administration

  The solicited systemic events included arthralgia (joint pain), fatigue (tiredness), headache, myalgia (muscle pain) and fever (pyrexia). Fever is defined as body temperature equal to or above (\>=) 38.0 degrees Celsius (°C). The preferred location for measuring temperature is the axilla. Any = occurrence of the event regardless of intensity grade.

  Within 7 days post vaccination (day of administration and 6 subsequent days post-first vaccination on Day 1)

• Stage 1: Number of Participants With Any Solicited Systemic Events After the Second Study Intervention Administration

  The solicited systemic events included arthralgia (joint pain), fatigue (tiredness), headache, myalgia (muscle pain) and fever (pyrexia). Fever is defined as body temperature equal to or above (≥) 38.0 degrees Celsius (°C). The preferred location for measuring temperature is the axilla. Any = occurrence of the event regardless of intensity grade.

  Within 7 days post vaccination (day of administration and 6 subsequent days post-second vaccination on Day 57)

• Stage 1: Number of Participants With Any Solicited Systemic Events After the Third Study Intervention Administration

  The solicited systemic events included arthralgia (joint pain), fatigue (tiredness), headache, myalgia (muscle pain) and fever (pyrexia). Fever is defined as body temperature equal to or above (≥) 38.0 degrees Celsius (°C). The preferred location for measuring temperature is the axilla. Any = occurrence of the event regardless of intensity grade.

  Within 7 days post vaccination (day of administration and 6 subsequent days post-third vaccination on Day 169)

• Stage 1: Number of Participants With Any Unsolicited Adverse Events (AE) After the First Study Intervention Administration

  An unsolicited AE is an AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited AE. Any = occurrence of the event regardless of intensity grade.

  Within 28 days post vaccination (day of administration and 27 subsequent days post-first vaccination on Day 1)

• Stage 1: Number of Participants With Any Unsolicited AEs After the Second Study Intervention Administration

  An unsolicited AE is an AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited AE. Any = occurrence of the event regardless of intensity grade.

  Within 28 days post vaccination (day of administration and 27 subsequent days post-second vaccination on Day 57)

• Stage 1: Number of Participants With Any Unsolicited AEs After the Third Study Intervention Administration

  An unsolicited AE is an AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited AE. Any = occurrence of the event regardless of intensity grade.

  Within 28 days post vaccination (day of administration and 27 subsequent days post-third vaccination on Day 169)

• Stage 1: Number of Participants With Any 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. Any = occurrence of the event regardless of intensity grade.

  From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (Day 197)

• Stage 1: Number of Participants With Any AEs/SAEs Leading to Withdrawal From the Study

  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. An AE is any untoward medical occurrence (an unfavourable/unintended sign - including an abnormal laboratory finding), symptom, or disease (new or exacerbated) in a clinical study participant that is temporally associated with the study intervention. A participant is considered to have withdrawn from the study if no new study procedure has been performed or no new information has been collected for him/her since the date of withdrawal/last contact. Any = occurrence of the event regardless of intensity grade.

  From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (Day 197)

• Stage 1: Number of Participants With Any AEs/SAEs Leading to Withholding Further Study Intervention Administration

  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. An AE is any untoward medical occurrence (an unfavourable/unintended sign - including an abnormal laboratory finding), symptom, or disease (new or exacerbated) in a clinical study participant that is temporally associated with the study intervention. AEs/SAEs that lead to withholding of the study intervention administration were considered under this outcome measure. Any = occurrence of the event regardless of intensity grade.

  From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (Day 197)

• Stage 1: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 8

  Assessed hepatic laboratory parameters included alanine aminotransferase \[ALT\] and aspartate aminotransferase \[AST\], and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 1 (baseline) and Day 8 hematological, renal and hepatic laboratory results are defined as follows: \<range\> (at baseline) - \<range\> (at timing) (e.g. Within (Baseline) - Within (Day 8)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  At Day 8 (7 days after the first study intervention administration) compared to Baseline (Day 1)

• Stage 1: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 64

  Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 57 (baseline) and Day 64 hematological, renal and hepatic laboratory results are defined as follows: \<range\> (at baseline) - \<range\> (at timing) (e.g. Within (Baseline) - Within (Day 64)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  At Day 64 (7 days after the second study intervention administration) compared to Baseline (Day 57)

• Stage 1: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 176

  Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 169 (baseline) and Day 176 hematological, renal and hepatic laboratory results are defined as follows: \<range\> (at baseline) - \<range\> (at timing) (e.g. Within (Baseline) - Within (Day 176)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  At Day 176 (7 days after the third study intervention administration) compared to Baseline (Day 169)

• Stage 1: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 29

  Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 1 (baseline) and Day 29 hematological, renal and hepatic laboratory results are defined as follows: \<range\> (at baseline) - \<range\> (at timing) (e.g. Within (Baseline) - Within (Day 29)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  At Day 29 (28 days after the first study intervention administration) compared to Baseline (Day 1)

• Stage 1: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 85

  Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 57 (baseline) and Day 85 hematological, renal and hepatic laboratory results are defined as follows: \<range\> (at baseline) - \<range\> (at timing) (e.g. Within (Baseline) - Within (Day 85)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  At Day 85 (28 days after the second study intervention administration) compared to Baseline (Day 57)

• Stage 1: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 197

  Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 169 (baseline) and Day 197 hematological, renal and hepatic laboratory results are defined as follows: \<range\> (at baseline) - \<range\> (at timing) (e.g. Within (Baseline) - Within (Day 197)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  At Day 197 (28 days after the third study intervention administration) compared to Baseline (Day 169)

• Stage 2: Number of Participants With Any Solicited Administration Site Events After the First Study Intervention Administration

  The solicited administration site events included redness (Erythema), pain and swelling. Data for solicited administration site events is presented for each intervention administered in each arm group. Any = occurrence of the event regardless of intensity grade.

  Within 7 days post vaccination (day of administration and 6 subsequent days post-first vaccination on Day 1)

• Stage 2: Number of Participants With Any Solicited Administration Site Events After the Second Study Intervention Administration

  The solicited administration site events included redness (Erythema), pain and swelling. Data for solicited administration site events is presented for each intervention administered in each arm group. Any = occurrence of the event regardless of intensity grade.

  Within 7 days post vaccination (day of administration and 6 subsequent days post-second vaccination on Day 57)

• Stage 2: Number of Participants With Any Solicited Administration Site Events After the Third Study Intervention Administration

  The solicited administration site events included redness (Erythema), pain and swelling. Data for solicited administration site events is presented for each intervention administered in each arm group. Any = occurrence of the event regardless of intensity grade.

  Within 7 days post vaccination (day of administration and 6 subsequent days post-third vaccination on Day 169)

• Stage 2: Number of Participants With Any Solicited Systemic Events After the First Study Intervention Administration

  The solicited systemic events included arthralgia (joint pain), fatigue (tiredness), headache, myalgia (muscle pain) and fever (pyrexia). Fever is defined as body temperature \>=38.0 degrees Celsius (°C). The preferred location for measuring temperature is the axilla. Any = occurrence of the event regardless of intensity grade.

  Within 7 days post vaccination (day of administration and 6 subsequent days post-first vaccination on Day 1)

• Stage 2: Number of Participants With Solicited Systemic Events After the Second Study Intervention Administration

  The solicited systemic events included arthralgia (joint pain), fatigue (tiredness), headache, myalgia (muscle pain) and fever (pyrexia). Fever is defined as body temperature \>=38.0 degrees Celsius (°C). The preferred location for measuring temperature is the axilla. Any = occurrence of the event regardless of intensity grade.

  Within 7 days post vaccination (day of administration and 6 subsequent days post-second vaccination on Day 57)

• Stage 2: Number of Participants With Any Solicited Systemic Events After the Third Study Intervention Administration

  The solicited systemic events included arthralgia (joint pain), fatigue (tiredness), headache, myalgia (muscle pain) and fever (pyrexia). Fever is defined as body temperature \>=38.0 degrees Celsius (°C). The preferred location for measuring temperature is the axilla. Any = occurrence of the event regardless of intensity grade.

  Within 7 days post vaccination (day of administration and 6 subsequent days post-third vaccination on Day 169)

• Stage 2: Number of Participants With Any Unsolicited AE After the First Study Intervention Administration

  An unsolicited AE is an AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited AE. Any = occurrence of the event regardless of intensity grade.

  Within 28 days post vaccination (day of administration and 27 subsequent days post-first vaccination on Day 1)

• Stage 2: Number of Participants With Any Unsolicited AE After the Second Study Intervention Administration

  An unsolicited AE is an AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited AE. Any = occurrence of the event regardless of intensity grade.

  Within 28 days post vaccination (day of administration and 27 subsequent days post-second vaccination on Day 57)

• Stage 2: Number of Participants With Any Unsolicited AE After the Third Study Intervention Administration

  An unsolicited AE is an AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited AE. Any = occurrence of the event regardless of intensity grade.

  Within 28 days post vaccination (day of administration and 27 subsequent days post-third vaccination on Day 169)

• Stage 2: Number of Participants With Any 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. Any = occurrence of the event regardless of intensity grade.

  From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (Day 197)

• Stage 2: Number of Participants With Any AEs/SAEs Leading to Withdrawal From the Study

  Any AEs including SAEs that lead to withdrawal from the study are considered under this outcome measure. A participant is considered to have withdrawn from the study if no new study procedure has been performed or no new information has been collected for him/her since the date of withdrawal/last contact. Any = occurrence of the event regardless of intensity grade.

  From first study intervention administration (Day 1) up to 28 days after the third study intervention (Day 197)

• Stage 2: Number of Participants With Any AEs/SAEs Leading to Withholding Further Study Intervention Administration

  AEs/SAEs that lead to withholding of the study intervention administration were considered under this outcome measure. Any = occurrence of the event regardless of intensity grade.

  From first study intervention administration (Day 1) up to 28 days after the third study intervention (Day 197)

• Stage 2: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 8

  Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 1 (baseline) and Day 8 hematological, renal and hepatic laboratory results are defined as follows: \<range\> (at baseline) - \<range\> (at timing) (e.g. Within (Baseline) - Within (Day 8)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  At Day 8 (7 days after the first study intervention administration) compared to Baseline (Day 1)

• Stage 2: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 64

  Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 57 (baseline) and Day 64 hematological, renal and hepatic laboratory results are defined as follows: \<range\> (at baseline) - \<range\> (at timing) (e.g. Within (Baseline) - Within (Day 64)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  At Day 64 (7 days after the second study intervention administration) compared to Baseline (Day 57)

• Stage 2: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 176

  Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 169 (baseline) and Day 176 hematological, renal and hepatic laboratory results are defined as follows: \<range\> (at baseline) - \<range\> (at timing) (e.g. Within (Baseline) - Within (Day 176)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  At Day 176 (7 days after the third study intervention administration) compared to Baseline (Day 169)

• Stage 2: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 29

  Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 1 (baseline) and Day 29 hematological, renal and hepatic laboratory results are defined as follows: \<range\> (at baseline) - \<range\> (at timing) (e.g. Within (Baseline) - Within (Day 29)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  At Day 29 (28 days after the first study intervention administration) compared to Baseline (Day 1)

• Stage 2: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 85

  Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 57 (baseline) and Day 85 hematological, renal and hepatic laboratory results are defined as follows: \<range\> (at baseline) - \<range\> (at timing) (e.g. Within (Baseline) - Within (Day 85)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  At Day 85 (28 days after the second study intervention administration) compared to Baseline (Day 57)

• Stage 2: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 197

  Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 169 (baseline) and Day 197 hematological, renal and hepatic laboratory results are defined as follows: \<range\> (at baseline) - \<range\> (at timing) (e.g. Within (Baseline) - Within (Day 197)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  At Day 197 (28 days after the third study intervention administration) compared to Baseline (Day 169)

Secondary Outcomes (12)

• Stage 1 and Stage 2: Number of Participants With Any SAEs

  From 28 days after the third study intervention administration (Day 197) up to study end (Day 337)

• Stage 1 and Stage 2: Number of Participants With Any AEs/SAEs Leading to Withdrawal From the Study

  From 28 days after the third study intervention administration (Day 197) up to study end (Day 337)

• Stage 1: Geometric Mean Concentrations (GMCs) of Anti-serotype Specific Immunoglobulin G (IgG) in Participants and Between Group Ratios for Anti-Vi Antigen (Ag) Total IgG

  At Days 1, 57, and 169 (before each study intervention administration) and at Days 29, 85, and 197 (28 days after each study intervention administration)

• Stage 1: GMCs of Anti-serotype Specific IgG in Participants and Between Group Ratios for Anti-S. Typhimurium OAg Total IgG and Anti-S. Enteritidis OAg Total IgG

  At Days 1, 57, and 169 (before each study intervention administration) and at Days 29, 85, and 197 (28 days after each study intervention administration)

• Stage 1: Geometric Mean Ratios (GMRs) for Anti-serotype Specific Immunoglobulin G (IgG) Concentrations

  At 28 days after each study intervention administration compared to each study intervention administration baseline (Day 29 versus Day 1, Day 85 versus Day 57 and Day 197 versus Day 169)

Study Arms (8)

Stage 1: Invasive nontyphoidal Salmonella (iNTS)-Typhoid conjugate vaccine (TCV) low dose group

EXPERIMENTAL

European participants were randomized to receive 3 doses of iNTS-TCV low dose vaccine and 3 doses of saline solution intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

Biological: Invasive nontyphoidal Salmonella-typhoid conjugate vaccine (iNTS-TCV) low dose; Other: Saline

Stage 1: iNTS-Generalized modules for membrane antigens (GMMA) + TCV low dose group

ACTIVE COMPARATOR

European participants were randomized to receive 3 doses of iNTS-GMMA low dose vaccine and 3 doses of TCV low dose vaccine intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

Biological: Invasive nontyphoidal Salmonella-generalized modules for membrane antigens vaccine (iNTS-GMMA) low dose; Biological: Typhoid conjugate vaccine (TCV) low dose

Stage 1: iNTS-TCV full dose group

EXPERIMENTAL

European participants were randomized to receive 3 doses of iNTS-TCV full dose vaccine and 3 doses of saline solution intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

Biological: Invasive nontyphoidal Salmonella-typhoid conjugate vaccine (iNTS-TCV) full dose; Other: Saline

Stage 1: iNTS-GMMA + TCV full dose group

ACTIVE COMPARATOR

European participants were randomized to receive 3 doses of iNTS-GMMA full dose vaccine and 3 doses of TCV full dose vaccine intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

Biological: Invasive nontyphoidal Salmonella-generalized modules for membrane antigens vaccine (iNTS-GMMA) full dose; Biological: Typhoid conjugate vaccine (TCV) full dose

Stage 1: Placebo group

PLACEBO COMPARATOR

European participants were randomized to receive 3 doses of Placebo and 3 doses of saline solution intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

Drug: Placebo; Other: Saline

Stage 2: iNTS-TCV full dose group

EXPERIMENTAL

African participants were randomized to receive 3 doses of iNTS-TCV full dose vaccine and 3 doses of saline solution intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

Biological: Invasive nontyphoidal Salmonella-typhoid conjugate vaccine (iNTS-TCV) full dose; Other: Saline

Stage 2: iNTS-GMMA + TCV full dose group

ACTIVE COMPARATOR

African participants were randomized to receive 3 doses of iNTS-GMMA full dose vaccine and 3 doses of TCV full dose intramuscularly, in different arms, on Day 1, Day 57 and Day 169.

Biological: Invasive nontyphoidal Salmonella-generalized modules for membrane antigens vaccine (iNTS-GMMA) full dose; Biological: Typhoid conjugate vaccine (TCV) full dose

Stage 2: Control group

ACTIVE COMPARATOR

African participants were randomized to receive MENVEO as comparator and 1 dose of saline on Day 1, BOOSTRIX as comparator and 1 dose of saline on Day 57 and TYPHIM VI as comparator and 1 dose of saline on Day 169.

Biological: GSK's Meningococcal A, C, Y and W-135 conjugate vaccine; Combination Product: GSK's Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine; Combination Product: Sanofi Pasteur's Typhoid Vi polysaccharide vaccine; Other: Saline

Interventions

Invasive nontyphoidal Salmonella-typhoid conjugate vaccine (iNTS-TCV) low dose BIOLOGICAL

3 doses of iNTS-TCV low dose vaccine administered intramuscularly at Day 1, Day 57, and Day 169 to participants in the iNTS-TCV low dose Group in Stage 1 (Europe).

Stage 1: Invasive nontyphoidal Salmonella (iNTS)-Typhoid conjugate vaccine (TCV) low dose group

Invasive nontyphoidal Salmonella-generalized modules for membrane antigens vaccine (iNTS-GMMA) low dose BIOLOGICAL

3 doses of iNTS-GMMA low dose vaccine administered intramuscularly at Day 1, Day 57, and Day 169 to participants in the iNTS-GMMA and TCV low doses Group in Stage 1 (Europe).

Stage 1: iNTS-Generalized modules for membrane antigens (GMMA) + TCV low dose group

Typhoid conjugate vaccine (TCV) low dose BIOLOGICAL

3 doses of TCV low dose vaccine administered intramuscularly at Day 1, Day 57, and Day 169 to participants in the iNTS-GMMA and TCV low doses Group in Stage 1 (Europe).

Stage 1: iNTS-Generalized modules for membrane antigens (GMMA) + TCV low dose group

Invasive nontyphoidal Salmonella-typhoid conjugate vaccine (iNTS-TCV) full dose BIOLOGICAL

3 doses of iNTS-TCV full dose vaccine administered intramuscularly at Day 1, Day 57, and Day 169 to participants in the iNTS-TCV full dose Group in Stage 1 (Europe) and to participants in iNTS-TCV full dose Group in Stage 2 (Africa).

Stage 1: iNTS-TCV full dose group; Stage 2: iNTS-TCV full dose group

Invasive nontyphoidal Salmonella-generalized modules for membrane antigens vaccine (iNTS-GMMA) full dose BIOLOGICAL

3 doses of iNTS-GMMA full dose vaccine administered intramuscularly at Day 1, Day 57, and Day 169 to participants in the iNTS-GMMA + TCV full dose Group in Stage 1 (Europe) and to participants in the iNTS-GMMA + TCV full dose Group in Stage 2 (Africa).

Stage 1: iNTS-GMMA + TCV full dose group; Stage 2: iNTS-GMMA + TCV full dose group

Typhoid conjugate vaccine (TCV) full dose BIOLOGICAL

3 doses of TCV full dose vaccine administered intramuscularly at Day 1, Day 57, and Day 169 to participants in the iNTS-GMMA + TCV full dose Group in Stage 1 (Europe) and to participants in the iNTS-GMMA + TCV full dose Group in Stage 2 (Africa).

Stage 1: iNTS-GMMA + TCV full dose group; Stage 2: iNTS-GMMA + TCV full dose group

GSK's Meningococcal A, C, Y and W-135 conjugate vaccine BIOLOGICAL

1 dose of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine administered intramuscularly at Day 1 to participants in the Control Group in Stage 2 (Africa).

Also known as: MENVEO

Stage 2: Control group

GSK's Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine COMBINATION_PRODUCT

1 dose of GSK's Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine administered intramuscularly at Day 57 to participants in the Control Group in Stage 2 (Africa).

Also known as: Boostrix

Stage 2: Control group

Sanofi Pasteur's Typhoid Vi polysaccharide vaccine COMBINATION_PRODUCT

1 dose of Sanofi Pasteur's Typhoid Vi polysaccharide vaccine administered intramuscularly at Day 169 to participants in the Control Group in Stage 2 (Africa).

Also known as: TYPHIM Vi

Stage 2: Control group

Placebo DRUG

3 doses of Placebo administered intramuscularly at Day 1, Day 57, and Day 169 to participants in the Placebo Group in Stage 1 (Europe).

Stage 1: Placebo group

Saline OTHER

3 doses of saline solution administered intramuscularly at Day 1, Day 57, and Day 169 to the participants.

Stage 1: Invasive nontyphoidal Salmonella (iNTS)-Typhoid conjugate vaccine (TCV) low dose group; Stage 1: Placebo group; Stage 1: iNTS-TCV full dose group; Stage 2: Control group; Stage 2: iNTS-TCV full dose group

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participants, 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 participant prior to performance of any study-specific procedure.
• Healthy participants as established by medical history, clinical examination, and laboratory assessment.
• Participant satisfying screening requirements.
• 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 nonchildbearing potential may be enrolled in the study. Nonchildbearing 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 trial 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.
• Blood sample for simultaneous follicle-stimulating hormone (FSH) and estradiol levels may be collected at the discretion of the Investigator to confirm non-reproductive potential according to local laboratory reference range.
• Genetic testing for HLA-B27 will be performed at Screening and only participants with a negative result will be allowed to participate in the study\*.
• Only for Stage 1.
• For Malawi (Stage 2), the participant lives in Blantyre and has agreed to remain in Blantyre for the study duration.

You may not qualify if:

• Known exposure to S. Typhi and nontyphoidal Salmonella confirmed by blood culture during the period starting 3 years prior to first study intervention administration confirmed using past medical history.
• History of any reaction or hypersensitivity associated with any component of the study interventions.
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by physical examination or laboratory screening tests.
• Recurrent history or uncontrolled neurological disorders or seizures.
• Any clinically significant\* hematological and/or biochemical laboratory abnormality.
• The Investigator should use his/her clinical judgment to decide which abnormalities are clinically significant from the panel of tests in the list of safety assays.
• Clinical conditions representing a contraindication to IM injections and/or 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.
• Confirmed positive COVID-19 polymerase chain reaction or lateral flow test during the period starting 28 days before the first administration of study vaccines (Day -28 to Day 1).
• Acute or chronic illness which may be severe enough to preclude participation.
• Any other clinical condition that, in the opinion of the Investigator, might pose additional risk to the participant due to participation in the study.
• Prior/Concomitant Therapy
• History of receiving any typhoid vaccine (Ty21a, Vi capsular polysaccharide, or TCV) in the participant's life.
• History of receiving any investigational iNTS or GMMA vaccines in the participant's life.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Biomedical Advanced Research and Development Authority: collaborator
• Wellcome Trust: collaborator
• Global Antimicrobial Resistance Innovation Fund-(GAMRIF): collaborator
• Bill and Melinda Gates Foundation: collaborator

Study Sites (2)

GSK Investigational Site

Edegem, 2650, Belgium

Location

GSK Investigational Site

Blantyre, Malawi

Location

MeSH Terms

Conditions

Salmonella Infections

Interventions

Meningococcal Vaccines; Boostrix; Vi polysaccharide vaccine, typhoid; Sodium Chloride

Condition Hierarchy (Ancestors)

Enterobacteriaceae Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

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: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Data will be collected in an observer-blind manner.
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2022
• First Posted: July 29, 2022
• Study Start: September 13, 2022
• Primary Completion: September 2, 2024
• Study Completion: January 7, 2025
• Last Updated: November 28, 2025
• Results First Posted: November 28, 2025

Record last verified: 2025-11

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, a 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

MA (1); BE (1)