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

A Phase 1/2a, Observer-blind, Randomized, Controlled, Two-stage, Multi-country Study to Evaluate the Safety, Reactogenicity, and Immune Response of the Trivalent Vaccine Against Invasive Nontyphoidal Salmonella (iNTS) and Typhoid Fever in Healthy European and African Adults

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.

Study Overview

• Status: Completed
• Conditions: Salmonella Infections
• Intervention / Treatment: 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; Biological: Typhoid conjugate vaccine (TCV) low dose; Other: Saline; Biological: Invasive nontyphoidal Salmonella-typhoid conjugate vaccine (iNTS-TCV) full dose; Biological: Invasive nontyphoidal Salmonella-generalized modules for membrane antigens vaccine (iNTS-GMMA) full dose; Biological: Typhoid conjugate vaccine (TCV) full dose; Drug: Placebo; 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

• Study Type: Interventional
• Enrollment (Actual): 155
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • GSK Investigational Site
• Malawi
  • Blantyre, Malawi
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria

• 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.

Exclusion criteria Medical Conditions

• 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.
• All medical conditions will be assessed by the Investigator who may use his/her discretion to decide if the participant meets the exclusion criteria.

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.
• Use of any investigational or non-registered product other than the study interventions during the period beginning 30 days (Days -30 to 1) before the first dose of study interventions, or their planned use during the study period.

• A vaccine not foreseen by the study protocol administered during the period starting at 14 days before the first dose and ending 28 days after the last dose of study interventions administration*, with the exception of flu vaccines or COVID-19 vaccine.

  • In case emergency mass vaccination for an unforeseen public health threat (eg, a pandemic) is recommended and/or organized by public health authorities outside the routine immunization program, the time period described above can be reduced if necessary for that vaccine, provided it is used according to the local governmental recommendations and that the Sponsor is notified accordingly.

When regulations allow, the recommended time intervals for administration of these vaccines are at least 7 days before or 7 days after (at least 14 days before or 14 days after in case of live vaccines) each dose of study intervention administration.

• Administration of long-acting immune-modifying drugs at any time during the study period (eg, infliximab).
• Administration of Ig and/or any blood products or plasma derivatives during the period starting 3 months before the administration of the first dose of study interventions or planned administration during the study period.
• 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 study intervention dose(s). For corticosteroids, this will mean prednisone equivalent ≥20 mg/day for adult participants. Inhaled and topical steroids are allowed.

Prior/Concurrent Clinical Study Experience

- Concurrently participating in another clinical trial, 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 (vaccine and drug).

Other Exclusions

• Pregnant or lactating female
• Female planning to become pregnant or planning to discontinue contraceptive precautions
• History of/current chronic alcohol consumption and/or drug abuse. This will be decided at the discretion of the Investigator. Chronic alcohol consumption is defined as one or more of the following:
• A prolonged period of frequent and heavy alcohol use
• The inability to control drinking once it has begun
• Physical dependence manifested by withdrawal symptoms when the individual stops using alcohol
• Tolerance or the need to use increasing amounts of alcohol to achieve the same effects
• A variety of social and/or legal problems arising from alcohol use.
• Any study personnel or their immediate dependents, family, or household members.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stage 1: Invasive nontyphoidal Salmonella (iNTS)-Typhoid conjugate vaccine (TCV) low dose group; 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; 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).; Other: Saline; 3 doses of saline solution administered intramuscularly at Day 1, Day 57, and Day 169 to the participants.
Active Comparator: Stage 1: iNTS-Generalized modules for membrane antigens (GMMA) + TCV low dose group; 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; 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).; Biological: Typhoid conjugate vaccine (TCV) low dose; 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).
Experimental: Stage 1: iNTS-TCV full dose group; 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.	Other: Saline; 3 doses of saline solution administered intramuscularly at Day 1, Day 57, and Day 169 to the participants.; Biological: Invasive nontyphoidal Salmonella-typhoid conjugate vaccine (iNTS-TCV) full dose; 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).
Active Comparator: Stage 1: iNTS-GMMA + TCV full dose group; 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; 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).; Biological: Typhoid conjugate vaccine (TCV) full dose; 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).
Placebo Comparator: Stage 1: Placebo group; 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.	Other: Saline; 3 doses of saline solution administered intramuscularly at Day 1, Day 57, and Day 169 to the participants.; Drug: Placebo; 3 doses of Placebo administered intramuscularly at Day 1, Day 57, and Day 169 to participants in the Placebo Group in Stage 1 (Europe).
Experimental: Stage 2: iNTS-TCV full dose group; 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.	Other: Saline; 3 doses of saline solution administered intramuscularly at Day 1, Day 57, and Day 169 to the participants.; Biological: Invasive nontyphoidal Salmonella-typhoid conjugate vaccine (iNTS-TCV) full dose; 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).
Active Comparator: Stage 2: iNTS-GMMA + TCV full dose group; 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; 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).; Biological: Typhoid conjugate vaccine (TCV) full dose; 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).
Active Comparator: Stage 2: Control group; 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.	Other: Saline; 3 doses of saline solution administered intramuscularly at Day 1, Day 57, and Day 169 to the participants.; Biological: GSK's Meningococcal A, C, Y and W-135 conjugate vaccine; 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).; Other Names: MENVEO; Combination product: GSK's Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine; 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).; Other Names: Boostrix; Combination product: Sanofi Pasteur's Typhoid Vi polysaccharide vaccine; 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).; Other Names: TYPHIM Vi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stage 1 and 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 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	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 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	Anti-Vi antigen (Ag) total IgG GMCs were assessed. Blood samples were collected at specified timepoint for each component as measured by Enzyme-Linked Immunosorbent Assay (ELISA). The lower limit of quantification (LLOQ) for antibody concentrations was >=2.2 microgram per milliliter (µg/mL). In case the measured antibody concentration fell below 2.2 µg/mL, a value of half the LLOQ value was imputed.	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	Anti-S. Typhimurium OAg total IgG, Anti-S. Enteritidis OAg total IgG GMCs were assessed. Blood samples were collected at specified timepoint for each component as measured by Enzyme-Linked Immunosorbent Assay (ELISA).	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	Anti-Vi antigen (Ag) total IgG, Anti-S. Typhimurium OAg total IgG, Anti-S. Enteritidis OAg total IgG within-participant GMRs were assessed. Blood samples were collected at specified timepoint for each component as measured by ELISA. Within participant GMRs were calculated as ratio of concentration in the post-vaccination timepoint to the pre-vaccination timepoint.	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)
Stage 1: Number of Participants Achieving at Least a 4 Fold Rise in Anti Serotype Specific Immunoglobulin G (IgG) Antibody Concentration for Each Antigen (Ag)	Anti-Vi Ag total IgG, Anti-S. Typhimurium OAg total IgG, Anti-S. Enteritidis OAg total IgG antibody concentrations were assessed. Blood samples were collected at specified timepoint for each component as measured by ELISA.	At Days 29, 85, and 197 (28 days after each study intervention administration) compared to Day 1 (first study intervention administration)
Stage 1: Number of Participants With Anti-Vi Ag IgG Antibody Concentrations Greater Than or Equal to (>=) 4.3 Micrograms Per Milliliter (µg/mL)	Blood samples were collected at specified timepoint for each component as measured by ELISA.	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 2: GMCs of Anti-serotype Specific IgG in Participants and Between Group Ratios for Anti-Vi Ag Total IgG	Anti-Vi Ag total IgG GMCs and between group ratios were assessed. Blood samples were collected at specified timepoint for each component as measured by ELISA.	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 2: 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	Anti-S. Typhimurium OAg total IgG and Anti-S. Enteritidis OAg total IgG GMCs and between group ratios were assessed. Blood samples were collected at specified timepoint for each component as measured by ELISA.	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 2: GMRs for Anti-serotype Specific Immunoglobulin G (IgG) Concentrations	Anti-Vi antigen (Ag) total IgG, Anti-S. Typhimurium OAg total IgG, Anti-S. Enteritidis OAg total IgG within-participant GMRs were assessed. Blood samples were collected at specified timepoint for each component as measured by ELISA. Within participant GMRs were calculated as ratio of concentration in the post-vaccination timepoint to the pre-vaccination timepoint.	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)
Stage 2: Number of Participants Achieving at Least a 4 Fold Rise in Anti Serotype Specific Immunoglobulin G (IgG) Antibody Concentration for Each Antigen (Ag)	Anti-Vi Ag total IgG, Anti-S. Typhimurium OAg total IgG, Anti-S. Enteritidis OAg total IgG antibody concentrations were assessed. Blood samples were collected at specified timepoint for each component as measured by ELISA.	At Days 29, 85, and 197 (28 days after each study intervention administration) compared to Day 1 (first study intervention administration baseline)
Stage 2: Number of Participants With Anti-Vi Ag IgG Antibody Concentrations >= 4.3 µg/mL	Blood samples were collected at specified timepoint for each component as measured by ELISA.	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)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: Bill and Melinda Gates Foundation; Wellcome Trust; Biomedical Advanced Research and Development Authority; Global Antimicrobial Resistance Innovation Fund-(GAMRIF)
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2022
• Primary Completion (Actual): September 2, 2024
• Study Completion (Actual): January 7, 2025

Study Registration Dates

• First Submitted: July 27, 2022
• First Submitted That Met QC Criteria: July 27, 2022
• First Posted (Actual): July 29, 2022

Study Record Updates

• Last Update Posted (Actual): November 28, 2025
• Last Update Submitted That Met QC Criteria: November 14, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Enterobacteriaceae Infections; Salmonella Infections; Inorganic Chemicals; Chlorine Compounds; Biological Products; Complex Mixtures; Bacterial Vaccines; Vaccines; Sodium Compounds; Chlorides; Hydrochloric Acid; Meningococcal Vaccines; Sodium Chloride; Boostrix; Vi polysaccharide vaccine, typhoid
• Other Study ID Numbers: 216152; 2021-005178-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No