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

Phase 1

Recruiting

• Conditions: Salmonella Infections
• Interventions: Biological: Invasive nontyphoidal Salmonella-generalized modules for membrane antigens vaccine (iNTS-GMMA) full dose; Biological: Invasive nontyphoidal Salmonella-typhoid conjugate vaccine (iNTS-TCV) full dose; Biological: Invasive nontyphoidal Salmonella-typhoid conjugate vaccine (iNTS-TCV) low dose; Biological: Invasive nontyphoidal Salmonella-generalized modules for membrane antigens vaccine (iNTS-GMMA) low dose; Drug: Placebo; Biological: GSK's Meningococcal A, C, Y and W-135 conjugate vaccine; Other: Saline; Biological: Typhoid conjugate vaccine (TCV) low dose; Biological: Typhoid conjugate vaccine (TCV) full dose; Combination Product: GSK's Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine; Combination Product: Sanofi Pasteur's Typhoid Vi polysaccharide vaccine

• Registration Number: NCT05480800
• Lead Sponsor: GlaxoSmithKline

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-07-27
• Study First Submitted QC: 2022-07-27
• Study First Posted: 2022-07-29
• Study Start: 2022-09-13
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-21
• Last Update Posted: 2024-02-22
• Primary Completion: 2024-12-18
• Study Completion: 2024-12-18

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 155

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
iNTS-GMMA and TCV full doses_1 Group	Invasive nontyphoidal Salmonella-generalized modules for membrane antigens vaccine (iNTS-GMMA) full dose	Participants 18 to 50 years of age in Stage 1 (Europe) randomized to receive 3 doses of iNTS-GMMA full dose vaccine and 3 doses of TCV full dose vaccine, administered in different arms, at Days 1, 57, and 169.
iNTS-TCV full dose_1 Group	Invasive nontyphoidal Salmonella-typhoid conjugate vaccine (iNTS-TCV) full dose	Participants 18 to 50 years of age in Stage 1 (Europe) randomized to receive 3 doses of iNTS-TCV full dose vaccine and 3 doses of saline solution, administered in different arms, at Days 1, 57, and 169.
iNTS-TCV full dose_1 Group	Saline	Participants 18 to 50 years of age in Stage 1 (Europe) randomized to receive 3 doses of iNTS-TCV full dose vaccine and 3 doses of saline solution, administered in different arms, at Days 1, 57, and 169.
iNTS-TCV low dose Group	Invasive nontyphoidal Salmonella-typhoid conjugate vaccine (iNTS-TCV) low dose	Participants 18 to 50 years of age in Stage 1 (Europe) randomized to receive 3 doses of iNTS-TCV low dose vaccine and 3 doses of saline solution, administered in different arms, at Days 1, 57, and 169.
iNTS-GMMA and TCV low doses Group	Invasive nontyphoidal Salmonella-generalized modules for membrane antigens vaccine (iNTS-GMMA) low dose	Participants 18 to 50 years of age in Stage 1 (Europe) randomized to receive 3 doses of iNTS-GMMA low dose vaccine and 3 doses of TCV low dose vaccine, administered in different arms, at Days 1, 57, and 169.
iNTS-TCV low dose Group	Saline	Participants 18 to 50 years of age in Stage 1 (Europe) randomized to receive 3 doses of iNTS-TCV low dose vaccine and 3 doses of saline solution, administered in different arms, at Days 1, 57, and 169.
Placebo _Step 1 Group	Saline	Participants 18 to 50 years of age in Stage 1 (Europe) randomized to receive 3 doses of placebo and 3 doses of saline solution, administered in different arms, at Days 1, 57, and 169.
Control_Stage 2 Group	Sanofi Pasteur's Typhoid Vi polysaccharide vaccine	Participants 18 to 50 years of age in Stage 2 (Africa) randomized to receive one dose of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine administered at Day 1, one dose of GSK's Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine administered at Day 57, one dose of Sanofi Pasteur's Typhoid Vi polysaccharide vaccine administered at Day 169, and 3 doses of saline solution administered at Days 1, 57 and 169.
iNTS-GMMA and TCV low doses Group	Typhoid conjugate vaccine (TCV) low dose	Participants 18 to 50 years of age in Stage 1 (Europe) randomized to receive 3 doses of iNTS-GMMA low dose vaccine and 3 doses of TCV low dose vaccine, administered in different arms, at Days 1, 57, and 169.
Placebo _Step 1 Group	Placebo	Participants 18 to 50 years of age in Stage 1 (Europe) randomized to receive 3 doses of placebo and 3 doses of saline solution, administered in different arms, at Days 1, 57, and 169.
iNTS-GMMA and TCV full doses_1 Group	Typhoid conjugate vaccine (TCV) full dose	Participants 18 to 50 years of age in Stage 1 (Europe) randomized to receive 3 doses of iNTS-GMMA full dose vaccine and 3 doses of TCV full dose vaccine, administered in different arms, at Days 1, 57, and 169.
Placebo_Step 2 Group	Placebo	Participants 18 to 50 years of age in Stage 1 (Europe) randomized to receive 3 doses of placebo and 3 doses of saline solution, administered in different arms, at Days 1, 57, and 169.
Placebo_Step 2 Group	Saline	Participants 18 to 50 years of age in Stage 1 (Europe) randomized to receive 3 doses of placebo and 3 doses of saline solution, administered in different arms, at Days 1, 57, and 169.
iNTS-TCV full dose_2 Group	Invasive nontyphoidal Salmonella-typhoid conjugate vaccine (iNTS-TCV) full dose	Participants 18 to 50 years of age in Stage 2 (Africa) randomized to receive 3 doses of iNTS-TCV full dose vaccine and 3 doses of saline solution, administered in different arms, at Days 1, 57, and 169.
iNTS-TCV full dose_2 Group	Saline	Participants 18 to 50 years of age in Stage 2 (Africa) randomized to receive 3 doses of iNTS-TCV full dose vaccine and 3 doses of saline solution, administered in different arms, at Days 1, 57, and 169.
iNTS-GMMA and TCV full doses_2 Group	Typhoid conjugate vaccine (TCV) full dose	Participants 18 to 50 years of age in Stage 2 (Africa) randomized to receive 3 doses of iNTS-GMMA full dose vaccine and 3 doses of TCV full dose vaccine, administered in different arms, at Days 1, 57, and 169.
Control_Stage 2 Group	GSK's Meningococcal A, C, Y and W-135 conjugate vaccine	Participants 18 to 50 years of age in Stage 2 (Africa) randomized to receive one dose of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine administered at Day 1, one dose of GSK's Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine administered at Day 57, one dose of Sanofi Pasteur's Typhoid Vi polysaccharide vaccine administered at Day 169, and 3 doses of saline solution administered at Days 1, 57 and 169.
Control_Stage 2 Group	GSK's Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine	Participants 18 to 50 years of age in Stage 2 (Africa) randomized to receive one dose of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine administered at Day 1, one dose of GSK's Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine administered at Day 57, one dose of Sanofi Pasteur's Typhoid Vi polysaccharide vaccine administered at Day 169, and 3 doses of saline solution administered at Days 1, 57 and 169.
iNTS-GMMA and TCV full doses_2 Group	Invasive nontyphoidal Salmonella-generalized modules for membrane antigens vaccine (iNTS-GMMA) full dose	Participants 18 to 50 years of age in Stage 2 (Africa) randomized to receive 3 doses of iNTS-GMMA full dose vaccine and 3 doses of TCV full dose vaccine, administered in different arms, at Days 1, 57, and 169.
Control_Stage 2 Group	Saline	Participants 18 to 50 years of age in Stage 2 (Africa) randomized to receive one dose of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine administered at Day 1, one dose of GSK's Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine administered at Day 57, one dose of Sanofi Pasteur's Typhoid Vi polysaccharide vaccine administered at Day 169, and 3 doses of saline solution administered at Days 1, 57 and 169.

Primary Outcome Measures

Name	Time	Method
Number of participants in Europe/Stage 1 with solicited systemic events after the first study intervention administration	During 7 days after the first study intervention administration occurring at Day 1	The solicited systemic events are fever, headache, myalgia, arthralgia, and fatigue. Fever is defined as body temperature equal to or above (≥) 38.0 degrees Celsius (°C)/100.4 degrees Fahrenheit (°F). The preferred location for measuring temperature is the axilla.
Number of participants in Africa/Stage 2 with solicited administration site events after the third study intervention administration	During 7 days after the third study intervention administration occurring at Day 169	The solicited administration site events are pain, redness, and swelling.
Number of participants in Europe/Stage 1 with solicited administration site events after the first study intervention administration	During 7 days after the first study intervention administration occurring at Day 1	The solicited administration site events are pain, redness, and swelling.
Number of participants in Europe/Stage 1 with solicited systemic events after the third study intervention administration	During 7 days after the third study intervention administration occurring at Day 169	The solicited systemic events are fever, headache, myalgia, arthralgia, and fatigue. Fever is defined as body temperature ≥ 38.0 °C/100.4 °F. The preferred location for measuring temperature is the axilla.
Number of participants in Europe/Stage 1 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 64	At Day 64 (7 days after the second study intervention administration)	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.
Number of participants in Africa/Stage 2 with unsolicited adverse events (AEs) after the second study intervention administration	During 28 days after the second study intervention administration occurring at Day 57	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.
Number of participants in Europe/Stage 1 with solicited administration site events after the second study intervention administration	During 7 days after the second study intervention administration occurring at Day 57	The solicited administration site events are pain, redness, and swelling.
Number of participants in Europe/Stage 1 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 176	At Day 176 (7 days after the third study intervention administration)	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.
Number of participants in Africa/Stage 2 with solicited administration site events after the first study intervention administration	During 7 days after the first study intervention administration occurring at Day 1	The solicited administration site events are pain, redness, and swelling.
Number of participants in Africa/Stage 2 with solicited systemic events after the first study intervention administration	During 7 days after the first study intervention administration occurring at Day 1	The solicited systemic events are fever, headache, myalgia, arthralgia, and fatigue. Fever is defined as body temperature ≥ 38.0 °C/100.4 °F. The preferred location for measuring temperature is the axilla.
Number of participants in Europe/Stage 1 with solicited administration site events after the third study intervention administration	During 7 days after the third study intervention administration occurring at Day 169	The solicited administration site events are pain, redness, and swelling.
Number of participants in Europe/Stage 1 with solicited systemic events after the second study intervention administration	During 7 days after the second study intervention administration occurring at Day 57	The solicited systemic events are fever, headache, myalgia, arthralgia, and fatigue. Fever is defined as body temperature ≥ 38.0 °C/100.4 °F. The preferred location for measuring temperature is the axilla.
Number of participants in Europe/Stage 1 with unsolicited adverse events (AEs) after the first study intervention administration	During 28 days after the first study intervention administration occurring at Day 1	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.
Number of participants in Europe/Stage 1 with unsolicited adverse events (AEs) after the second study intervention administration	During 28 days after the second study intervention administration occurring at Day 57	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.
Number of participants in Europe/Stage 1 with AEs/SAEs leading to withdrawal from the study and/or withholding doses of study intervention	From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (Day 197)	Any AEs including SAEs that lead to discontinuation of study intervention and/or the study are considered under this outcome measure.
Number of participants in Europe/Stage 1 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 85	At Day 85 (28 days after the second study intervention administration)	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.
Number of participants in Europe/Stage 1 with unsolicited adverse events (AEs) after the third study intervention administration	During 28 days after the third study intervention administration occurring at Day 169	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.
Number of participants in Europe/Stage 1 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 29	At Day 29 (28 days after the first study intervention administration)	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.
Number of participants in Europe/Stage 1 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 197	At Day 197 (28 days after the third study intervention administration)	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.
Number of participants in Africa/Stage 2 with solicited administration site events after the second study intervention administration	During 7 days after the second study intervention administration occurring at Day 57	The solicited administration site events are pain, redness, and swelling.
Number of participants in Africa/Stage 2 with solicited systemic events after the second study intervention administration	During 7 days after the second study intervention administration occurring at Day 57	The solicited systemic events are fever, headache, myalgia, arthralgia, and fatigue. Fever is defined as body temperature ≥ 38.0 °C/100.4 °F. The preferred location for measuring temperature is the axilla.
Number of participants in Africa/Stage 2 with unsolicited adverse events (AEs) after the third study intervention administration	During 28 days after the third study intervention administration occurring at Day 169	Any 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.
Number of participants in Africa/Stage 2 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 8	At Day 8 (7 days after the first study intervention administration)	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.
Number of participants in Europe/Stage 1 with serious adverse events (SAEs)	From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (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, represents a congenital anomaly/birth defect in the offspring of a study participant or abnormal pregnancy outcomes.
Number of participants in Europe/Stage 1 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 8	At Day 8 (7 days after the first study intervention administration)	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.
Number of participants in Africa/Stage 2 with unsolicited adverse events (AEs) after the first study intervention administration	During 28 days after the first study intervention administration occurring at Day 1	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.
Number of participants in Africa/Stage 2 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 29	At Day 29 (28 days after the first study intervention administration)	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.
Number of participants in Africa/Stage 2 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 85	At Day 85 (28 days after the second study intervention administration)	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.
Number of participants in Africa/Stage 2 with solicited systemic events after the third study intervention administration	During 7 days after the third study intervention administration occurring at Day 169	The solicited systemic events are fever, headache, myalgia, arthralgia, and fatigue. Fever is defined as body temperature ≥ 38.0 °C/100.4 °F. The preferred location for measuring temperature is the axilla.
Number of participants in Africa/Stage 2 with serious adverse events (SAEs)	From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (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, represents a congenital anomaly/birth defect in the offspring of a study participant or abnormal pregnancy outcomes.
Number of participants in Africa/Stage 2 with AEs/SAEs leading to withdrawal from the study and/or withholding doses of study intervention	From first study intervention administration (Day 1) up to 28 days after the third study intervention (Day 197)	Any AEs including SAEs that lead to discontinuation of study intervention and/or the study are considered under this outcome measure.
Number of participants in Africa/Stage 2 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 64	At Day 64 (7 days after the second study intervention administration)	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.
Number of participants in Africa/Stage 2 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 176	At Day 176 (7 days after the third study intervention administration)	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.
Number of participants in Africa/Stage 2 with deviations from normal or baseline values for hematological, renal, and hepatic panels test results at Day 197	At Day 197 (28 days after the third study intervention administration)	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.

Secondary Outcome Measures

Name	Time	Method
Number of participants with serious adverse events (SAEs)	From 28 days after the third study intervention administration (Day 197) up to study end (Day 337)	An SAE is defined as any untoward medical occurrence that results in death, is lifethreatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in disability/incapacity, represents a congenital anomaly/birth defect in the offspring of a study participant or abnormal pregnancy outcomes.
Number of participants in Africa/Stage 2 achieving, for each antigen (Ag), at least a 4-fold rise in anti-serotype specific immunoglobulin G (IgG) antibody concentration	At Days 29, 85 and 197 (28 days after each study intervention administration) compared to Day 1 (first study intervention administration baseline)	Anti-S. Typhi Vi Ag total IgG, Anti-S. Typhimurium O Ag total IgG, Anti-S. Enteritidis O Ag total IgG antibody concentrations are assessed.
Anti-serotype specific immunoglobulin G (IgG) within-participant geometric mean ratios (GMRs) in participants in Europe/Stage 1	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)	Anti-S. Typhi Vi antigen (Ag) total IgG, Anti-S. Typhimurium O Ag total IgG, Anti-S. Enteritidis O Ag total IgG within-participant GMRs are assessed.
Number of participants in Europe/Stage 1 achieving, for each antigen (Ag), at least a 4-fold rise in anti-serotype specific immunoglobulin G (IgG) antibody concentration	At Days 29, 85, and 197 (28 days after each study intervention administration) compared to Day 1 (first study intervention administration baseline)	Anti-S. Typhi Vi Ag total IgG, Anti-S. Typhimurium O Ag total IgG, Anti-S. Enteritidis O Ag total IgG antibody concentrations are assessed.
Anti-serotype specific immunoglobulin G (IgG) within-participant geometric mean ratios (GMRs) in participants in Africa/Stage 2	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)	Anti-S. Typhi Vi Ag total IgG, Anti-S. Typhimurium O Ag total IgG, Anti-S. Enteritidis O Ag total IgG within-participant GMRs are assessed.
Number of participants with AEs/SAEs leading to withdrawal from the study	From 28 days after third study intervention administration (Day 197) up to Day 337	Any AEs including SAEs that lead to discontinuation of the study are considered under this outcome measure.
Anti-serotype specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) in participants in Africa/Stage 2, and between-group ratios	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)	Anti-S. Typhi Vi Ag total IgG, Anti-S. Typhimurium O Ag total IgG, Anti-S. Enteritidis O Ag total IgG GMCs and between-group ratios are assessed.
Number of participants in Africa/Stage 2 with Anti-S. Typhi Vi antigen (Ag) immunoglobulin G (IgG) antibody concentrations equivalent to ≥ 4.3 micrograms per milliliter (µg/mL)	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)
Anti-serotype specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) in participants in Europe/Stage 1, and between-group ratios	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)	Anti-S. Typhi Vi antigen (Ag) total IgG, Anti-S. Typhimurium O Ag total IgG, Anti-S. Enteritidis O Ag total IgG GMCs and between-group ratios are assessed.
Number of participants in Europe/Stage 1 with Anti-S. typhi Vi Ag IgG antibody concentrations equivalent to ≥ 4.3 micrograms per milliliter (µg/mL)	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)

Trial Locations

Locations (1)

GSK Investigational Site; 🇲🇼 Blantyre 3, Malawi