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

Official 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

Overview

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).

Interventions

• Biological Low dose of iNTS-TCV
  Low dose of iNTS-TCV vaccine will be administered.
• Biological Full dose of iNTS-TCV
  Full dose of iNTS-TCV vaccine will be administered.
• Biological TYPHIBEV
  TYPHIBEV vaccine will be administered.
• Combination product Prevenar 13
  Prevenar 13 vaccine will be administered.
• Combination product Nimenrix
  Nimenrix vaccine will be administered.
• Drug Saline
  Saline will be administered.

Primary outcome measures

• Number of participants with solicited administration site events during 7 days after each study intervention administration [for infants 6 MOA] [Time frame: 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] [Time frame: 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] [Time frame: At Day 1, Day 85 and Day 337]
• Number of participants with serious adverse events (SAEs) [for infants 6 MOA] [Time frame: 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] [Time frame: From the first study intervention administration (Day 1) until study end (Day 505).]
• Number of participants with laboratory abnormalities [for infants 6 MOA] [Time frame: 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] [Time frame: 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] [Time frame: 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] [Time frame: At Day 1, Day 57 and Day 232]
• Number of participants with SAEs [for infants 6 WOA] [Time frame: From the first study intervention administration (Day 1) until study end (Day 400).]

Secondary outcome measures (8)

• GMC of anti-STm OAg, anti-SEn OAg and anti-Vi IgG before each study intervention administration [for infants 6 MOA] [Time frame: 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] [Time frame: 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] [Time frame: 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] [Time frame: 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] [Time frame: 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)]
• Number of participants with anti-Vi IgG concentrations greater than or equal to (>=)2.0 micrograms per milliliter (µg/mL) and >=4.3 µg/mL [for infants 6 MOA] [Time frame: Before each study intervention administration (Day 1, Day 85 and Day 337) and 28 days after each study intervention administration (Day 29, Day 113 and Day 365)]
• Number of participants achieving at least 2-fold and 4fold increase in antiserotype specific IgG concentrations [for infants 6 WOA] [Time frame: At 28 days after each study intervention administration (Day 29, Day 85 and Day 260), compared with before the first study intervention administration (Day 1)]
• Number of participants with anti-Vi IgG concentrations >=2.0 µg/mL and >=4.3 µg/mL [for infants 6 WOA] [Time frame: Before each study intervention administration (Day 1, Day 57 and Day 232) and 28 days after each study intervention administration (Day 29, Day 85 and Day 260)]

Eligibility criteria

Inclusion criteria

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.

Exclusion criteria

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 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.
• 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 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).
• Have clinically significant (moderate in severity) acute illness on the day of vaccination (temporary exclusion if remains age-eligible within the allowed dosing window).
• 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 a positive rapid diagnostic test (RDT) (or blood film) for malaria (temporary exclusion if remains age-eligible).
• 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.
• Have used traditional or local herbal medications, including topical medications, in the 14 days prior to enrollment
• Have a history of chronic administration of immune-modifying drugs (defined as more than 14 consecutive days) and/or planned use of long-acting immune-modifying treatments at any time up to the end of the study.

• for corticosteroids, this will mean prednisone equivalent >=0.5mg/kg/day with maximum of 20 mg/day for pediatric participants). The use of inhaled/per nasal and topical steroids are allowed.
• long-acting immune-modifying drugs including among others immunotherapy (eg, TNF-inhibitors), monoclonal antibodies, antitumoral medication.
• Prior receipt of a typhoid vaccine, or an experimental iNTS or GMMA vaccine.
• Use of any investigational or non-registered product (drug, vaccine, or medical device) other than the study intervention during the period starting 28 days before the first dose of study intervention (Day -28 to Day 1), or 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 14 days after the last dose of study interventions administration for live vaccines or 7 days in case of inactivated vaccines, with the exception of flu vaccines or Coronavirus disease 2019 (COVID-19) vaccine which may be considered on a case-by-case basis.
• Have been administered immunoglobulins and/or any blood products or plasma derivatives, or bone marrow transplantation, during the period starting 3 months before the first dose of study interventions or planned administration during the study period.
• Concurrently participating in another interventional clinical study, 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 (drug or invasive medical device).
• Have any other factor which, in the opinion of the Investigator, might pose additional risk to the participant or substantially compromise data quality or the evaluation of study endpoints.
• Any study personnel or their immediate dependents, family, or household members.
• Have plans to travel outside the study area for an extended duration during the period of study participation.
• Child in care.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Prevention

Study locations

The Gambia · 1 center

• GSK Investigational Site — Banjul

Identifiers

NCT: NCT07286370 · 223550

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗