A bivalent Typhoid and Paratyphoid A conjugate investigational vaccine aimed to prevent both typhoid and paratyphoid enteric fever in infants and older age groups has been developed by GlaxoSmithKline (GSK). The purpose of this first-time-in-human study is to evaluate the safety and immunogenicity profile of a low and a full dose of the investigational vaccine, formulated with or without adjuvant, administered in 2 doses, 24 weeks apart, in healthy adults 18 to 50 years of age in Europe.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
97
2 doses of TYP04A Low Dose without Alum investigational vaccine administered intramuscularly as a priming dose on Day 1 and a booster dose on Day 169.
2 doses of TYP04B Full Dose without Alum investigational vaccine administered intramuscularly as a priming dose on Day 1 and a booster dose on Day 169.
2 doses of TYP03A Low Dose with Alum investigational vaccine administered intramuscularly as a priming dose on Day 1 and a booster dose on Day 169.
GSK Investigational Site
Edegem, Belgium
Number of Participants With Solicited Administration-site Events After the First Vaccination
Solicited administration site events included pain, redness, and swelling.
Time frame: From Day 1 to Day 7
Number of Participants With Solicited Administration-site Events After the Second Vaccination
Solicited administration site events included pain, redness, and swelling.
Time frame: From Day 169 to Day 175
Number of Participants With Solicited Systemic Events After the First Vaccination
The solicited systemic events included arthralgia (joint pain), fatigue (tiredness), fever, headache, and myalgia (muscle pain). Fever is defined as body temperature more than or equal to (\>=) 38.0 degrees Celsius (°C).
Time frame: From Day 1 to Day 7
Number of Participants With Solicited Systemic Events After the Second Vaccination
The solicited systemic events included arthralgia (joint pain), fatigue (tiredness), fever, headache, and myalgia (muscle pain).
Time frame: From Day 169 to Day 175
Number of Participants With Unsolicited Adverse Events (AEs) After the First Vaccination
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.
Time frame: From Day 1 to Day 28
Number of Participants With Unsolicited Adverse Events After the Second Vaccination
An unsolicited adverse event is defined as an adverse event 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.
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2 doses of TYP03B Full Dose with Alum investigational vaccine administered intramuscularly as a priming dose on Day 1 and a booster dose on Day 169.
1 dose of Sanofi Pasteur's Typhoid Vi polysaccharide vaccine administered intramuscularly, at Day 1, to participants in the control group.
1 dose of GSK's Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine administered intramuscularly, at Day 169, to participants in the control group.
Time frame: From Day 169 to Day 196
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.
Time frame: From Day 1 to Day 197
Number of Participants With 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.
Time frame: From Day 1 to Day 197
Number of Participants With 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. SAEs that lead to withholding of the study intervention administration were considered under this outcome measure.
Time frame: From Day 1 to Day 197
Number of Participants With AEs Leading to Withholding Further Study Intervention Administration
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 that lead to withholding of the study intervention administration were considered under this outcome measure.
Time frame: From Day 1 to Day 197
Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 8
Assessed hematological laboratory parameters include basophils, eosinophils, erythrocytes, hemoglobin, hematocrit, lymphocytes, monocytes, neutrophils, platelets, leukocytes. Hepatic laboratory parameters include alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\] and renal laboratory parameters include creatinine and blood urea. Categories reported when comparing Day 1 (baseline) and Day 8 hematological, renal and hepatic laboratory results are defined as follows: \<parameter\>-\<range at baseline\>-\<range at timing\> (e.g. ALT-Within-Within). Range level being classified as below, within or above the normal range.
Time frame: At Day 8 compared to Day 1 (Baseline)
Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 176
Assessed hematological laboratory parameters include basophils, eosinophils, erythrocytes, hemoglobin, hematocrit, lymphocytes, monocytes, neutrophils, platelets, leukocytes. Hepatic laboratory parameters include alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\] and renal laboratory parameters include creatinine and blood urea. Categories reported when comparing Day 169 (baseline) and Day 176 hematological, renal and hepatic laboratory results are defined as follows: \<parameter\>-\<range at baseline\>-\<range at timing\> (e.g. ALT-Within-Within). Range level being classified as below, within or above the normal range.
Time frame: At Day 176 compared to Day 169 (Baseline)
Number of Participants With Any SAE
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.
Time frame: From Day 197 to Day 337
Number of Participants With 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.
Time frame: From Day 197 to Day 337
Geometric Mean Concentrations (GMCs) of Anti-Vi Antigen Immunoglobulin G (IgG) Antibody Concentrations
Anti-Vi specific IgG antibodies were measured by an anti-Vi IgG Enzyme-Linked Immunosorbent Assay (ELISA) kit. Blood samples were collected at specified timepoints.
Time frame: At Day 1 (pre-dose 1), Day 29, Day 169 (pre-Dose 2), Day 176 and Day 197
Geometric Mean Ratio (GMR) for Anti-Vi Antigen IgG Antibody Concentrations
Anti-Vi specific IgG antibodies were measured by an anti-Vi IgG ELISA kit. Blood samples were collected at specified timepoints. Within participant GMRs were calculated as ratio of concentration in the post-vaccination timepoint to the pre-vaccination timepoint.
Time frame: At Day 29, Day 169, Day 176, and Day 197 compared to Day 1 (baseline)
GMR for Anti-Vi Antigen IgG Antibody Concentrations
Anti-Vi specific IgG antibodies were measured by an anti-Vi IgG ELISA kit. Blood samples were collected at specified timepoints. Within participant GMRs were calculated as ratio of concentration in the post-vaccination timepoint to the pre-vaccination timepoint.
Time frame: At Day 176 and Day 197 compared to Day 169 (baseline)
GMC of Anti-O:2 IgG Antibody Concentrations
Anti-O:2 IgG antibodies in serum were measured by an ELISA assay. Blood samples were collected at specified timepoints.
Time frame: At Day 1 (pre-dose 1), Day 29, Day 169 (pre-dose 2), Day 176 and Day 197
GMR for Anti-O:2 IgG Antibody Concentrations
Anti-O:2 IgG antibodies in serum were measured by an ELISA assay. Blood samples were collected at specified timepoints. Within participant GMRs were calculated as ratio of concentration in the post-vaccination timepoint to the pre-vaccination timepoint.
Time frame: At Day 29, Day 169, Day 176, and Day 197 compared to Day 1 (baseline)
GMR for Anti-O:2 IgG Antibody Concentrations
Anti-O:2 IgG antibodies in serum were measured by an ELISA assay. Blood samples were collected at specified timepoint. Within participant GMRs were calculated as ratio of concentration in the post-vaccination timepoint to the pre-vaccination timepoint.
Time frame: At Day 176 and Day 197 compared to Day 169 (baseline)
Number of Participants With Anti-Vi Antigen 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.
Time frame: At Day 1, Day 29, Day 169, Day 176 and Day 197
Number of Participants With Anti-Vi Antigen IgG Antibody Concentrations >= 2.0 µg/mL
Blood samples were collected at specified timepoint for each component as measured by ELISA.
Time frame: At Day 1, Day 29, Day 169, Day 176 and Day 197
Number of Participants With at Least 4-fold Increase in Anti-O:2 IgG Antibody Concentrations
Blood samples were collected at specified timepoint for each component as measured by ELISA. 4-fold increase was defined as 4 times the baseline value of anti-O:2 IgG antibody concentrations.
Time frame: At Day 29, Day 169, Day 176 and Day 197 compared to Day 1 (baseline)