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: Recruiting
• Conditions: Salmonella Infections
• Intervention / Treatment: Biological: Invasive nontyphoidal Salmonella-typhoid conjugate vaccine (iNTS-TCV) low dose; Other: Saline; Biological: Invasive nontyphoidal Salmonella-generalized modules for membrane antigens vaccine (iNTS-GMMA) low dose; Biological: Typhoid conjugate vaccine (TCV) low dose; Drug: Placebo; 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; 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 (Estimated): 155
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
• Study Contact Backup: Name: EU GSK Clinical Trials Call Center; Phone Number: +44 (0) 20 89904466; Email: GSKClinicalSupportHD@gsk.com

Study Locations

• Belgium
  • Edegem, Belgium, 2650
    • Recruiting
    • GSK Investigational Site
    • Principal Investigator: Kanchanamala Withanage
    • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
    • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
• Malawi
  • Blantyre 3, Malawi
    • Recruiting
    • GSK Investigational Site
    • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
    • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
    • Principal Investigator: Melita Alison Gordon

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

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: iNTS-TCV low dose Group; 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.	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 participants in the iNTS-TCV low dose, Placebo_Step 1, iNTS-TCV full dose_1, Placebo_Step 2 groups in Stage 1 (Europe) and to participants in iNTS-TCV full dose_2 and Control_Stage 2 groups in Stage 2 (Africa).
Active Comparator: iNTS-GMMA and TCV low doses Group; 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.	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).
Placebo Comparator: Placebo _Step 1 Group; 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.	Other: Saline; 3 doses of saline solution administered intramuscularly at Day 1, Day 57, and Day 169 to participants in the iNTS-TCV low dose, Placebo_Step 1, iNTS-TCV full dose_1, Placebo_Step 2 groups in Stage 1 (Europe) and to participants in iNTS-TCV full dose_2 and Control_Stage 2 groups in Stage 2 (Africa).; Drug: Placebo; 3 doses of Placebo administered intramuscularly at Day 1, Day 57, and Day 169 to participants in the Placebo_Step 1 and Placebo_Step 2 in Stage 1 (Europe).
Experimental: iNTS-TCV full dose_1 Group; 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.	Other: Saline; 3 doses of saline solution administered intramuscularly at Day 1, Day 57, and Day 169 to participants in the iNTS-TCV low dose, Placebo_Step 1, iNTS-TCV full dose_1, Placebo_Step 2 groups in Stage 1 (Europe) and to participants in iNTS-TCV full dose_2 and Control_Stage 2 groups in Stage 2 (Africa).; 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_1 Group in Stage 1 (Europe) and to participants in iNTS-TCV full dose_2 Group in Stage 2 (Africa).
Active Comparator: iNTS-GMMA and TCV full doses_1 Group; 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.	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 and TCV full doses_1 Group in Stage 1 (Europe) and to participants in the iNTS-GMMA and TCV full doses_2 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 and TCV full doses_1 Group in Stage 1 (Europe) and to participants in the iNTS-GMMA and TCV full doses_2 Group in Stage 2 (Africa).
Placebo Comparator: Placebo_Step 2 Group; 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.	Other: Saline; 3 doses of saline solution administered intramuscularly at Day 1, Day 57, and Day 169 to participants in the iNTS-TCV low dose, Placebo_Step 1, iNTS-TCV full dose_1, Placebo_Step 2 groups in Stage 1 (Europe) and to participants in iNTS-TCV full dose_2 and Control_Stage 2 groups in Stage 2 (Africa).; Drug: Placebo; 3 doses of Placebo administered intramuscularly at Day 1, Day 57, and Day 169 to participants in the Placebo_Step 1 and Placebo_Step 2 in Stage 1 (Europe).
Experimental: iNTS-TCV full dose_2 Group; 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.	Other: Saline; 3 doses of saline solution administered intramuscularly at Day 1, Day 57, and Day 169 to participants in the iNTS-TCV low dose, Placebo_Step 1, iNTS-TCV full dose_1, Placebo_Step 2 groups in Stage 1 (Europe) and to participants in iNTS-TCV full dose_2 and Control_Stage 2 groups in Stage 2 (Africa).; 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_1 Group in Stage 1 (Europe) and to participants in iNTS-TCV full dose_2 Group in Stage 2 (Africa).
Active Comparator: iNTS-GMMA and TCV full doses_2 Group; 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.	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 and TCV full doses_1 Group in Stage 1 (Europe) and to participants in the iNTS-GMMA and TCV full doses_2 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 and TCV full doses_1 Group in Stage 1 (Europe) and to participants in the iNTS-GMMA and TCV full doses_2 Group in Stage 2 (Africa).
Active Comparator: Control_Stage 2 Group; 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.	Other: Saline; 3 doses of saline solution administered intramuscularly at Day 1, Day 57, and Day 169 to participants in the iNTS-TCV low dose, Placebo_Step 1, iNTS-TCV full dose_1, Placebo_Step 2 groups in Stage 1 (Europe) and to participants in iNTS-TCV full dose_2 and Control_Stage 2 groups in Stage 2 (Africa).; 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_Stage 2 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_Stage 2 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_Stage 2 Group in Stage 2 (Africa).; Other Names: TYPHIM Vi

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants in Europe/Stage 1 with solicited administration site events after the first study intervention administration	The solicited administration site events are pain, redness, and swelling.	During 7 days after the first study intervention administration occurring at Day 1
Number of participants in Europe/Stage 1 with solicited administration site events after the second study intervention administration	The solicited administration site events are pain, redness, and swelling.	During 7 days after the second study intervention administration occurring at Day 57
Number of participants in Europe/Stage 1 with solicited administration site events after the third study intervention administration	The solicited administration site events are pain, redness, and swelling.	During 7 days after the third study intervention administration occurring at Day 169
Number of participants in Europe/Stage 1 with solicited systemic events after the first study intervention administration	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.	During 7 days after the first study intervention administration occurring at Day 1
Number of participants in Europe/Stage 1 with solicited systemic events after the second study intervention administration	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.	During 7 days after the second study intervention administration occurring at Day 57
Number of participants in Europe/Stage 1 with solicited systemic events after the third study intervention administration	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.	During 7 days after the third study intervention administration occurring at Day 169
Number of participants in Europe/Stage 1 with unsolicited adverse events (AEs) 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.	During 28 days after the first study intervention administration occurring at Day 1
Number of participants in Europe/Stage 1 with unsolicited adverse events (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.	During 28 days after the second study intervention administration occurring at Day 57
Number of participants in Europe/Stage 1 with unsolicited adverse events (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.	During 28 days after the third study intervention administration occurring at Day 169
Number of participants in Europe/Stage 1 with serious adverse events (SAEs)	An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in disability/incapacity, represents a congenital anomaly/birth defect in the offspring of a study participant or abnormal pregnancy outcomes.	From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (Day 197)
Number of participants in Europe/Stage 1 with AEs/SAEs leading to withdrawal from the study and/or withholding doses of study intervention	Any AEs including SAEs that lead to discontinuation of study intervention and/or the study are considered under this outcome measure.	From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (Day 197)
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	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.	At Day 8 (7 days after the first study intervention administration)
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	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.	At Day 64 (7 days after the second study intervention administration)
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	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.	At Day 176 (7 days after the third study intervention administration)
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	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.	At Day 29 (28 days after the first study intervention administration)
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	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.	At Day 85 (28 days after the second study intervention administration)
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	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.	At Day 197 (28 days after the third study intervention administration)
Number of participants in Africa/Stage 2 with solicited administration site events after the first study intervention administration	The solicited administration site events are pain, redness, and swelling.	During 7 days after the first study intervention administration occurring at Day 1
Number of participants in Africa/Stage 2 with solicited administration site events after the second study intervention administration	The solicited administration site events are pain, redness, and swelling.	During 7 days after the second study intervention administration occurring at Day 57
Number of participants in Africa/Stage 2 with solicited administration site events after the third study intervention administration	The solicited administration site events are pain, redness, and swelling.	During 7 days after the third study intervention administration occurring at Day 169
Number of participants in Africa/Stage 2 with solicited systemic events after the first study intervention administration	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.	During 7 days after the first study intervention administration occurring at Day 1
Number of participants in Africa/Stage 2 with solicited systemic events after the second study intervention administration	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.	During 7 days after the second study intervention administration occurring at Day 57
Number of participants in Africa/Stage 2 with solicited systemic events after the third study intervention administration	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.	During 7 days after the third study intervention administration occurring at Day 169
Number of participants in Africa/Stage 2 with unsolicited adverse events (AEs) 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.	During 28 days after the first study intervention administration occurring at Day 1
Number of participants in Africa/Stage 2 with unsolicited adverse events (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.	During 28 days after the second study intervention administration occurring at Day 57
Number of participants in Africa/Stage 2 with unsolicited adverse events (AEs) after the third study intervention administration	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.	During 28 days after the third study intervention administration occurring at Day 169
Number of participants in Africa/Stage 2 with serious adverse events (SAEs)	An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in disability/incapacity, represents a congenital anomaly/birth defect in the offspring of a study participant or abnormal pregnancy outcomes.	From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (Day 197)
Number of participants in Africa/Stage 2 with AEs/SAEs leading to withdrawal from the study and/or withholding doses of study intervention	Any AEs including SAEs that lead to discontinuation of study intervention and/or the study are considered under this outcome measure.	From first study intervention administration (Day 1) up to 28 days after the third study intervention (Day 197)
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	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.	At Day 8 (7 days after the first study intervention administration)
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	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.	At Day 64 (7 days after the second study intervention administration)
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	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.	At Day 176 (7 days after the third study intervention administration)
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	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.	At Day 29 (28 days after the first study intervention administration)
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	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.	At Day 85 (28 days after the second study intervention administration)
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	Panel tests include measures of leukocytes, platelets, hemoglobin, alanine aminotransferase, aspartate aminotransferase, urea/blood urea nitrogen, and creatinine.	At Day 197 (28 days after the third study intervention administration)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with serious adverse events (SAEs)	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.	From 28 days after the third study intervention administration (Day 197) up to study end (Day 337)
Number of participants with AEs/SAEs leading to withdrawal from the study	Any AEs including SAEs that lead to discontinuation of the study are considered under this outcome measure.	From 28 days after third study intervention administration (Day 197) up to Day 337
Anti-serotype specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) in participants in Europe/Stage 1, and between-group ratios	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.	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) within-participant geometric mean ratios (GMRs) in participants in Europe/Stage 1	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.	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)
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	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.	At Days 29, 85, and 197 (28 days after each study intervention administration) compared to Day 1 (first study intervention administration baseline)
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)
Anti-serotype specific immunoglobulin G (IgG) geometric mean concentrations (GMCs) in participants in Africa/Stage 2, and between-group ratios	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.	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) within-participant geometric mean ratios (GMRs) in participants in Africa/Stage 2	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.	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)
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	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.	At Days 29, 85 and 197 (28 days after each study intervention administration) compared to Day 1 (first study intervention administration baseline)
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)

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 (Estimated): December 18, 2024
• Study Completion (Estimated): December 18, 2024

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 (Estimated): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 21, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Enterobacteriaceae Infections; Typhoid Fever; Salmonella Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• 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