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

NCT07286370 | Recruiting Phase 2 DMC

• 1 other identifier: 223550
• Study Type: interventional
• Target: 537
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate 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) vaccine in infants with the first dose administered at 6 months of age (MOA) or 6 weeks of age (WOA).

Conditions

Salmonella Infections

Keywords

Salmonella-typhoid conjugate (iNTS-TCV) vaccine; Typhoid fever; Infants; Safety; Reactogenicity; Immunogenicity

Outcome Measures

Primary Outcomes (16)

• Number of participants with solicited administration site events during 7 days after each study intervention administration [for infants 6 MOA]

  Solicited administration site events included pain, redness, and swelling.

  At Day 1, Day 85 and Day 337

• Number of participants with solicited systemic events during 7 days after each study intervention administration [for infants 6 MOA]

  Solicited systemic events included Fever, Irritability/Fussiness, Loss of appetite, Somnolence (sleepiness/drowsiness) and Vomiting. Fever is defined as body temperature more than or equal to (\>=) 37.5 degrees Celsius (°C), measured from axilla.

  At Day 1, Day 85 and Day 337

• Number of participants with unsolicited adverse events (AEs) during 28 days after each study intervention administration [for infants 6 MOA]

  An unsolicited AE is defined as an AE that was either not included in the list of solicited events or could be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events.

  At Day 1, Day 85 and Day 337

• Number of participants with serious adverse events (SAEs) [for infants 6 MOA]

  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.

  From the first study intervention administration (Day 1) until study end (Day 505).

• Number of participants with AEs/SAEs leading to withdrawal from the study or discontinuation of study intervention [for infants 6 MOA]

  From the first study intervention administration (Day 1) until study end (Day 505).

• Number of participants with laboratory abnormalities [for infants 6 MOA]

  At 7 days after each study intervention administration (Day 8, Day 92 and Day 344).

• Number of participants with solicited administration site events during 7 days after each study intervention administration [for infants 6 WOA]

  At Day 1, Day 57 and Day 232

• Number of participants with solicited systemic events during 7 days after each study intervention administration [for infants 6 WOA]

  At Day 1, Day 57 and Day 232

• Number of participants with unsolicited adverse events (AEs) during 28 days after each study intervention administration [for infants 6 WOA]

  At Day 1, Day 57 and Day 232

• Number of participants with SAEs [for infants 6 WOA]

  From the first study intervention administration (Day 1) until study end (Day 400).

• Number of participants with AEs/SAEs leading to withdrawal from the study or discontinuation of study intervention [for infants 6 WOA]

  From the first study intervention administration (Day 1) until study end (Day 400).

• Number of participants with laboratory abnormalities [for infants 6 WOA]

  At 7 days after each study intervention administration (Day 8, Day 64 and Day 239).

• Geometric Mean concentration (GMC) ratio of anti- S. typhimurium (STm) and anti- Salmonella Enteritidis (SEn) O-antigen (OAg) immunoglobulin G (IgG) [for infants 6 MOA]

  At 28 days after the second study intervention administration (Day 113)

• GMC ratio of anti-Vi IgG [for infants 6 MOA]

  At 28 days after the first study intervention administration (Day 29)

• GMC ratio of anti-STm and anti-SEn OAg IgG concentrations [for infants 6 WOA]

  At 28 days after the third study intervention administration (Day 260)

• GMC ratio of anti-Vi IgG [for infants 6 WOA]

  At 28 days after the third study intervention administration (Day 260)

Secondary Outcomes (8)

• GMC of anti-STm OAg, anti-SEn OAg and anti-Vi IgG before each study intervention administration [for infants 6 MOA]

  At Day 1, Day 85 and Day 337

• GMC of anti-STm OAg, anti-SEn OAg and anti-Vi IgG 28 days after each study intervention administration [for infants 6 MOA]

  At Day 29, Day 113 and Day 365

• GMC of anti-STm OAg, anti-SEn OAg and anti-Vi IgG before each study intervention administration [for infants 6 WOA]

  At Day 1, Day 57 and Day 232

• GMC of anti-STm OAg, anti-SEn OAg and anti-Vi IgG 28 days after each study intervention administration [for infants 6 WOA]

  At Day 29, Day 85 and Day 260

• Number of participants achieving at least 2-fold and 4fold increase in antiserotype specific IgG concentrations [for infants 6 MOA]

  At 28 days after each study intervention administration (Day 29, Day 113 and Day 365) compared with before the first study intervention administration (Day 1)

Study Arms (14)

Step 1a- Group 1 iNTS-TCV low dose (6 MOA)

EXPERIMENTAL

Participants 6 MOA receive 3 doses of a low dose of iNTS-TCV at Day 1, Day 85 and Day 337.

Biological: Low dose of iNTS-TCV

Step 1a Group 2- Control group (6MOA)

ACTIVE COMPARATOR

Participants 6 MOA receive TYPHIBEV at Day 1, pneumococcal polysaccharide conjugate vaccine (13 valent) (Prevenar 13) at Day 85, and Nimenrix at Day 337.

Biological: TYPHIBEV; Combination Product: Prevenar 13; Combination Product: Nimenrix

Step 1b Group 3- iNTS-TCV full dose (6 MOA)

EXPERIMENTAL

Participants 6 MOA receive 3 doses of a full dose of iNTS-TCV at Day 1, Day 85 and Day 337.

Biological: Full dose of iNTS-TCV

Step 1b Group 4- iNTS-TCV full dose + Prevenar 13 (6 MOA)

EXPERIMENTAL

Participants 6 MOA receive 2 doses of a full dose of iNTS-TCV at Day 1 and Day 337 and 1 dose of Prevenar 13 at Day 85.

Biological: Full dose of iNTS-TCV; Combination Product: Prevenar 13

Step 1b Group 5- Control Group (6 MOA)

ACTIVE COMPARATOR

Participants 6 MOA receive TYPHIBEV at Day 1, Prevenar 13 at Day 85, and Nimenrix at Day 337.

Biological: TYPHIBEV; Combination Product: Prevenar 13; Combination Product: Nimenrix

Step 1c- Group 6- iNTS-TCV low dose (6 WOA)

EXPERIMENTAL

Participants 6 WOA receive 3 doses of a low dose of iNTS-TCV at Day 1, Day 57 and Day 232.

Biological: Low dose of iNTS-TCV

Step 1c- Group 7- Control Group (6 WOA)

ACTIVE COMPARATOR

Participants 6 WOA receive 2 doses of Nimenrix at Day 1 and Day 57, and 1 dose of TYPHIBEV at Day 232

Biological: TYPHIBEV; Combination Product: Nimenrix

Step 1d- Group 8- iNTS-TCV full dose (6 WOA)

EXPERIMENTAL

Participants 6 WOA receive 3 doses of a full dose of iNTS-TCV at Day 1, Day 57 and Day 232.

Biological: Full dose of iNTS-TCV

Step 1d- Group 9- Control Group (6 WOA)

ACTIVE COMPARATOR

Participants 6 WOA receive 2 doses of Nimenrix at Day 1 and Day 57, and 1 dose of TYPHIBEV at Day 232

Biological: TYPHIBEV; Combination Product: Nimenrix

Step 2- Group 10- iNTS-TCV low dose (6 WOA)

EXPERIMENTAL

Participants 6 WOA receive 3 doses of a low dose of iNTS-TCV at Day 1, Day 57 and Day 232.

Biological: Low dose of iNTS-TCV

Step 2- Group 11- iNTS-TCV low dose+ Saline Group (6 WOA)

EXPERIMENTAL

Participants 6 WOA receive 1 dose of a saline on Day 1 and 2 doses of low dose of iNTS-TCV at Day 57 and Day 232.

Biological: Low dose of iNTS-TCV; Drug: Saline

Step 2- Group 12- iNTS-TCV full dose (6 WOA)

EXPERIMENTAL

Participants 6 WOA receive 3 doses of a full dose of iNTS-TCV at Day 1, Day 57 and Day 232.

Biological: Full dose of iNTS-TCV

Step 2- Group 13- iNTS-TCV full dose+ Saline Group (6 WOA)

EXPERIMENTAL

Participants 6 WOA receive 1 dose of saline on Day 1 and 2 doses of full dose of iNTS-TCV at Day 57 and Day 232.

Biological: Full dose of iNTS-TCV; Drug: Saline

Step 2- Group 14 - Control Group (6 WOA)

ACTIVE COMPARATOR

Participants 6 WOA receive 2 doses of Nimenrix at Day 1 and Day 57, and 1 dose of TYPHIBEV at Day 232

Biological: TYPHIBEV; Combination Product: Nimenrix

Interventions

TYPHIBEV BIOLOGICAL

TYPHIBEV vaccine will be administered.

Also known as: Typhoid Vi-CRM197 conjugate vaccine

Step 1a Group 2- Control group (6MOA); Step 1b Group 5- Control Group (6 MOA); Step 1c- Group 7- Control Group (6 WOA); Step 1d- Group 9- Control Group (6 WOA); Step 2- Group 14 - Control Group (6 WOA)

Low dose of iNTS-TCV BIOLOGICAL

Low dose of iNTS-TCV vaccine will be administered.

Step 1a- Group 1 iNTS-TCV low dose (6 MOA); Step 1c- Group 6- iNTS-TCV low dose (6 WOA); Step 2- Group 10- iNTS-TCV low dose (6 WOA); Step 2- Group 11- iNTS-TCV low dose+ Saline Group (6 WOA)

Prevenar 13 COMBINATION_PRODUCT

Prevenar 13 vaccine will be administered.

Step 1a Group 2- Control group (6MOA); Step 1b Group 4- iNTS-TCV full dose + Prevenar 13 (6 MOA); Step 1b Group 5- Control Group (6 MOA)

Nimenrix COMBINATION_PRODUCT

Nimenrix vaccine will be administered.

Also known as: meningococcal groups A, C, W-135 and Y conjugate vaccine

Step 1a Group 2- Control group (6MOA); Step 1b Group 5- Control Group (6 MOA); Step 1c- Group 7- Control Group (6 WOA); Step 1d- Group 9- Control Group (6 WOA); Step 2- Group 14 - Control Group (6 WOA)

Saline DRUG

Saline will be administered.

Step 2- Group 11- iNTS-TCV low dose+ Saline Group (6 WOA); Step 2- Group 13- iNTS-TCV full dose+ Saline Group (6 WOA)

Full dose of iNTS-TCV BIOLOGICAL

Full dose of iNTS-TCV vaccine will be administered.

Step 1b Group 3- iNTS-TCV full dose (6 MOA); Step 1b Group 4- iNTS-TCV full dose + Prevenar 13 (6 MOA); Step 1d- Group 8- iNTS-TCV full dose (6 WOA); Step 2- Group 12- iNTS-TCV full dose (6 WOA); Step 2- Group 13- iNTS-TCV full dose+ Saline Group (6 WOA)

Eligibility Criteria

• Age: 6 Weeks - 6 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Participants must:
• Have signed/thumb-printed, voluntary, informed consent provided for them by their parent/Legally Authorized Representative (LAR) prior to performance of any study-specific procedure.
• Be a male or female infant aged 6 months (±2 weeks) or 6 weeks (+2 weeks) of age at the time of the first study vaccination.
• Have a parent/LAR, who can and will comply with the requirements of the protocol.
• Healthy as established by medical history, clinical examination, and laboratory assessment.
• Have received all routine childhood vaccinations as per the age.
• Have been born at full term (\>=37 weeks gestation) based on maternal report and additional antenatal records if available.
• Have a parent/LAR who is willing to avoid the administration of local herbal/traditional medications (including topical treatments) throughout the study period and who is willing to consult, as applicable, the study team prior to the use on other medications including over the-counter medications not supplied by the study team (except in the case of an emergency) throughout the study period.
• Have a readily identifiable place of residence within a reasonable travelling distance of the study site.
• Have a parent/LAR with a means of telephone contact.
• Have a parent/LAR who is willing to avoid vaccinations not provided by the study team throughout the participant's enrollment in the study. All routine Essential Programme on Immunization (EPI) vaccines due during the study (outside those given concurrently with the study vaccines/controls) will also be administered by the study team.

You may not qualify if:

• Participants must not:
• Have had a known infection with STm, SEn or S. Typhi.
• Have a history of allergic reactions to any prior vaccination or components of the investigational or control vaccines.
• Hypersensitivity to latex.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the study interventions.
• Have any history of anaphylaxis or other life-threatening allergic reactions.
• Have any confirmed or suspected congenital or acquired immunosuppressive or immunodeficient condition, based on medical history and physical examination.
• Have a bleeding or coagulation disorder contraindicating intramuscular injections or any other condition that in the judgment of the Investigator would make intramuscular injection unsafe.
• Have any screening/last pre-dosing safety laboratory test (if applicable) with a toxicity score of ≥3 or a value judged to be clinically significant by the study clinician.
• Have HIV, hepatitis B, or hepatitis C based on baseline serological assessment (these serological evaluations are only required during the screening phase).
• Be known to have been vertically exposed to HIV based on maternal history and baseline serological assessment in the participant (maternal screening for HIV will not be undertaken).
• Have major congenital defects, as assessed by the Investigator.
• Recurrent history or uncontrolled neurological disorders or any neuroinflammatory (including, but not limited to demyelinating disorders, encephalitis or myelitis of any origin), congenital neurological conditions, encephalopathies, or any history of seizures.
• Be malnourished at Screening Visit, defined as WHO weight for length Z-score less than -2 standard deviation (SD).
• Any other clinical condition that might pose additional risk to the participant as a result of participation in the clinical study.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Banjul, The Gambia

RECRUITING

MeSH Terms

Conditions

Salmonella Infections; Typhoid Fever

Interventions

13-valent pneumococcal vaccine; Sodium Chloride

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Central Study Contacts

US GSK Clinical Trials Call Center

CONTACT

877-379-3718; GSKClinicalSupportHD@gsk.com

EU GSK Clinical Trials Call Center

CONTACT

+44 (0) 20 89904466; GSKClinicalSupportHD@gsk.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Data will be collected in an observer-blind manner.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2025
• First Posted: December 16, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 27, 2028
• Study Completion (Estimated): April 27, 2028
• Last Updated: April 20, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.
• Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 months.

Locations

TH (1)