Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202507692744228 Date of Registration: 31/07/2025
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A Phase 2a study to evaluate the safety, reactogenicity, and immune response of the GVGH iNTS-TCV vaccine against invasive nontyphoidal Salmonella (iNTS) disease and Typhoid Fever in infants, in Africa
Official scientific title A Phase 2a, observer-blind, randomized, controlled, age-de-escalation, single-center interventional study to evaluate the safety, reactogenicity, and immune response of the GVGH iNTS-TCV vaccine against invasive nontyphoidal Salmonella (iNTS) disease and Typhoid Fever, including dose and schedule finding in infants, in Africa
Brief summary describing the background and objectives of the trial The estimated death toll from invasive nontyphoidal Salmonella (iNTS) disease and Typhoid Fever, combined was 90 000 deaths in sub-Saharan Africa in 2019. GlaxoSmithKline (GSK) Vaccines Institute for Global Health (GVGH) is developing a new candidate trivalent vaccine (GVGH invasive nontyphoidal Salmonella [iNTS]-typhoid conjugate vaccine [TCV]) against Salmonella Typhimurium (STm), Salmonella Enteritidis (SEn), and Salmonella Typhi. The trivalent iNTS-TCV vaccine has been tested in a first-in-human Phase 1/2a study (NCT05480800) that evaluated the safety, reactogenicity, and the immunogenicity of the primary response induced in European and African adults. The purpose of the current Phase 2a study is to evaluate the safety, reactogenicity, and the immunogenicity induced by this vaccine in infants with the first dose administered either at 6 MOA or 6 weeks of age (WOA)
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied invasive nontyphoidal Salmonella (iNTS) disease and Typhoid Fever
Purpose of the trial Prevention: Vaccines
Anticipated trial start date 01/11/2025
Actual trial start date
Anticipated date of last follow up 27/10/2027
Actual Last follow-up date
Anticipated target sample size (number of participants) 537
Actual target sample size (number of participants)
Recruitment status Not yet recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Permuted block randomization Allocation Sequence/Code was not concealed Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Step 1a Group 1 iNTS TCV low dose at 6 MOA Participants 6 MOA receive 3 doses of a low dose of iNTS-TCV at Day 1, Day 85 and Day 337. Participants 6 MOA receive 3 doses of a low dose of iNTS-TCV at Day 1, Day 85 and Day 337. Participants 6 MOA receive 3 doses of a low dose of iNTS-TCV at Day 1, Day 85 and Day 337. 15
Control Group Step 1a Control group 2 controls used in this group are TYPHIBEV Prevenar 13 and Nimenrix Participants 6 MOA receive TYPHIBEV at Day 1, Prevenar 13 at Day 85, and Nimenrix at Day 337. Participants 6 MOA receive TYPHIBEV at Day 1, Prevenar 13 at Day 85, and Nimenrix at Day 337. Participants 6 MOA receive TYPHIBEV at Day 1, Prevenar 13 at Day 85, and Nimenrix at Day 337. 3 Active-Treatment of Control Group
Experimental Group Step 1b Group 3 iNTS TCV full dose at 6 MOA Participants 6 MOA receive 3 doses of a full dose of iNTS-TCV at Day 1, Day 85 and Day 337. Participants 6 MOA receive 3 doses of a full dose of iNTS-TCV at Day 1, Day 85 and Day 337. Participants 6 MOA receive 3 doses of a full dose of iNTS-TCV at Day 1, Day 85 and Day 337. 78
Experimental Group Step 1b Group 4 iNTS TCV full dose including Prevenar 13 at 6 MOA Participants 6 MOA receive 2 doses of a full dose of iNTS-TCV at Day 1 and Day 337 and 1 dose of pneumococcal polysaccharide conjugate vaccine (13 valent) (Prevenar 13) at Day 85. Participants 6 MOA receive 2 doses of a full dose of iNTS-TCV at Day 1 and Day 337 and 1 dose of pneumococcal polysaccharide conjugate vaccine (13 valent) (Prevenar 13) at Day 85. Participants 6 MOA receive 2 doses of a full dose of iNTS-TCV at Day 1 and Day 337 and 1 dose of pneumococcal polysaccharide conjugate vaccine (13 valent) (Prevenar 13) at Day 85. 78
Control Group Step 1b Group 5 Control Group at 6 MOA including TYPHIBEV Prevenar 13 and Nimenrix Participants 6 MOA receive TYPHIBEV at Day 1, Prevenar 13 at Day 85, and Nimenrix at Day 337. Participants 6 MOA receive TYPHIBEV at Day 1, Prevenar 13 at Day 85, and Nimenrix at Day 337. Participants 6 MOA receive TYPHIBEV at Day 1, Prevenar 13 at Day 85, and Nimenrix at Day 337. 39 Active-Treatment of Control Group
Experimental Group Step 1c Group 6 iNTS TCV low dose at 6 WOA Participants 6 WOA receive 3 doses of a low dose of iNTS-TCV at Day 1, Day 57 and Day Participants 6 WOA receive 3 doses of a low dose of iNTS-TCV at Day 1, Day 57 and Day Participants 6 WOA receive 3 doses of a low dose of iNTS-TCV at Day 1, Day 57 and Day 10
Control Group Step 1c Group 7 Control Group at 6 WOA including Nimenrix and TYPHIB Participants 6 WOA receive 2 doses of Nimenrix at Day 1 and Day 57, and 1 dose of TYPHIBEV at Day 232 Participants 6 WOA receive 2 doses of Nimenrix at Day 1 and Day 57, and 1 dose of TYPHIBEV at Day 232 Participants 6 WOA receive 2 doses of Nimenrix at Day 1 and Day 57, and 1 dose of TYPHIBEV at Day 232 2 Active-Treatment of Control Group
Experimental Group Step 1d Group 8 iNTS TCV full dose at 6 WOA Participants 6 WOA receive 3 doses of a full dose of iNTS-TCV at Day 1, Day 57 and Day 232. Participants 6 WOA receive 3 doses of a full dose of iNTS-TCV at Day 1, Day 57 and Day 232. Participants 6 WOA receive 3 doses of a full dose of iNTS-TCV at Day 1, Day 57 and Day 232. 10
Control Group Step 1d Group 9 Control Group at 6 WOA including Nimenrix and TYPHIBE Participants 6 WOA receive 2 doses of Nimenrix at Day 1 and Day 57, and 1 dose of TYPHIBEV at Day 232 Participants 6 WOA receive 2 doses of Nimenrix at Day 1 and Day 57, and 1 dose of TYPHIBEV at Day 232 Participants 6 WOA receive 2 doses of Nimenrix at Day 1 and Day 57, and 1 dose of TYPHIBEV at Day 232 2 Active-Treatment of Control Group
Experimental Group Step 2 Group 10 iNTS TCV low dose at 6 WOA Participants 6 WOA receive 3 doses of a low dose of iNTS-TCV at Day 1, Day 57 and Day 232. Participants 6 WOA receive 3 doses of a low dose of iNTS-TCV at Day 1, Day 57 and Day 232. Participants 6 WOA receive 3 doses of a low dose of iNTS-TCV at Day 1, Day 57 and Day 232. 60
Experimental Group Step 2 Group 11 iNTS TCV low dose and Saline at 6 WOA 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. 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. 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. 60
Experimental Group Step 2 Group 12 iNTS TCV full dose at 6 WOA Participants 6 WOA receive 3 doses of a full dose of iNTS-TCV at Day 1, Day 57 and Day 232. Participants 6 WOA receive 3 doses of a full dose of iNTS-TCV at Day 1, Day 57 and Day 232. Participants 6 WOA receive 3 doses of a full dose of iNTS-TCV at Day 1, Day 57 and Day 232. 60
Experimental Group Step 2 Group 13 iNTS TCV full dose and Saline Group at 6 WOA 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. 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. 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. 60
Control Group Step 2 Group 14 Control Group at 6 WOA including Nimenrix and TYPHIBE Participants 6 WOA receive 2 doses of Nimenrix at Day 1 and Day 57, and 1 dose of TYPHIBEV at Day 232 Participants 6 WOA receive 2 doses of Nimenrix at Day 1 and Day 57, and 1 dose of TYPHIBEV at Day 232 Participants 6 WOA receive 2 doses of Nimenrix at Day 1 and Day 57, and 1 dose of TYPHIBEV at Day 232 60 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Have signed/thumb-printed, voluntary, informed consent provided for them by their parent/LAR prior to performance of any study-specific procedure. 2. Be a male or female infant aged 6 months (±2 weeks) (Steps 1a and 1b) or 6 weeks (+2 weeks) of age (Steps 1c, 1d, or 2) at the time of the first study vaccination. 3. Have a parent/LAR, who, in the opinion of the Investigator, can and will comply with the requirements of the protocol (eg, returning for follow-up visits). 4. Healthy as established by medical history, clinical examination, and laboratory assessment. 5. Have received all routine childhood vaccinations as per the age. 6. Have been born at full term (≥37 weeks gestation) based on maternal report and additional antenatal records if available. 7. 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. 8. Have a readily identifiable place of residence within a reasonable travelling distance of the study site. 9. Have a parent/LAR with a means of telephone contact. 10. 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 EPI vaccines due during the study (outside those given concurrently with the study vaccines/controls) will also be administered by the study team. include but not limited to Participants must not: 1. Have had a known infection with STm, SEn or S. Typhi (eg, history of microbiologically confirmed iNTS infection). 2. history of allergic reactions to any prior vaccination or components of the investigational or control vaccines. 3. Hypersensitivity to latex. 4. History of any reaction or hypersensitivity likely to be exacerbated by any component of the study interventions. 5. history of anaphylaxis or other life-threatening allergic reactions. 6. Have any confirmed or suspected congenital or acquired immunosuppressive or immunodeficient condition, based on medical history and physical examination. 7. Any acute or chronic, clinically significant pulmonary, cardiovascular, hepatobiliary, gastrointestinal, renal, neurological, or hematological abnormality or illness, as determined by medical history, physical examination, and (when applicable) baseline laboratory assessments. Known sickle cells disease (but not sickle cell trait) is an exclusion. 8. 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. 9. Have a documented fever (axillary temperature ≥37.5ºC) at the time of enrollment/dosing or within the 48 hours preceding dosing (temporary exclusion if remains age-eligible/within the allowed interval of dosing). 10. Have clinically significant (moderate in severity) acute illness on the day of vaccination (temporary exclusion if remains age-eligible within the allowed dosing window). 11. 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. 12. Have HIV, hepatitis B, or hepatitis C based on baseline serological assessment (these serological evaluations are only required during the screening phase). 13. Be known to vertically exposed to HIV Infant: 1 Month(s)-12 Month(s) 6 Week(s) 6 Month(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
No 21/07/2025 MRC joint ethics committee
Ethics Committee Address
Street address City Postal code Country
MRC Unit The Gambia at LSHTM, Atlantic Road, Fajara Banjul POBox 273 Gambia
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Occurrence of solicited administration site and systemic events 7 days after each study intervention administration
Primary Outcome Occurrence of unsolicited AEs during 28 days after each study intervention administration
Primary Outcome Occurrence of SAEs from the first study intervention administration until study end
Primary Outcome • Occurrence of AEs/SAEs leading to withdrawal from the study or discontinuation of study intervention from the first study intervention administration until study end
Primary Outcome • Occurrence of deviations from reference ranges or baseline values for hematological, renal, and hepatic panels test results at 7 days after each study intervention administration
Primary Outcome • Anti-STm and anti-SEn OAg IgG concentrations as measured by ELISA 28 days after the second study intervention administration
Primary Outcome • Anti-Vi IgG concentrations as measured by ELISA 28 days after the first study intervention administration
Primary Outcome • Anti-STm and anti-SEn OAg IgG concentrations as measured by ELISA 28 days after the third study intervention administration
Primary Outcome • Anti-Vi IgG concentrations as measured by ELISA 28 days after the third study intervention administration
Secondary Outcome • Anti-STm, anti-SEn OAg, and anti-Vi IgG concentrations as measured by ELISA before each study intervention administration and 28 days after each study intervention administration
Secondary Outcome • Participants achieving at least 2 fold and 4-fold increase in anti serotype specific IgG as measured by ELISA. 28 days after each study intervention administration compared with before the first study intervention administration Day 1
Secondary Outcome • Participants with anti-Vi IgG concentrations ≥2.0 µg/mL and ≥4.3 µg/mL as measured by ELISA. before each study intervention administration and 28 days after each study intervention
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
The Medical Research Council Unit The Gambia Atlantic Boulevard Fajara Banjul PO Box 27 Gambia
FUNDING SOURCES
Name of source Street address City Postal code Country
GlaxoSmithKline Biologicals SA Rue De L Institut 89 Rixensart 1330 Belgium
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor GlaxoSmithKline Biologicals SA Rue De LInstitut 89 Rixensart 1330 Belgium Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Ed Clarke ed.clarke@lshtm.ac.uk 002207039732 Atlantic Boulevard, Fajara
City Postal code Country Position/Affiliation
Banjul Box 273 Gambia Head of Infant Immunology
Role Name Email Phone Street address
Public Enquiries Rita La Gaetana rita.x.la-gaetana@gsk.com 00393401700275 Via Fiorentina 1
City Postal code Country Position/Affiliation
Siena Italy Head of regulatory affairs at GSK GVGH
Role Name Email Phone Street address
Scientific Enquiries Ashwani Arora ashwani.k.arora@gsk.com 00393469887366 Via Fiorentina 1
City Postal code Country Position/Affiliation
Siena Italy Head of Clinical Development at GSK GVGH
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes  Plan to Share IPD = Yes o IPD Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK’s data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/ o IPD Sharing 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 Study Protocol GSK will register results summaries submission within 6 months of primary/study completion date. summaries will also be posted on national or regional clinical study registers. The full study report will be made available upon request, after decision on marketing authorization by regulatory authorities.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information
Section Name Field Name Date Reason Old Value Updated Value
Reporting IPD description 29/07/2025 respond to the comment by reviewer and provide more details on this point. GSK will register results summaries submission within 6 months of primary/study completion date.  Plan to Share IPD = Yes o IPD Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK’s data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/ o IPD Sharing 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