A Phase 1, Observer-blind, Randomised, Controlled, Single-centre Study to Evaluate the Safety, Reactogenicity, and Immune Responses to an Adjuvanted and Non-adjuvanted Conjugate Vaccine Against Salmonella Typhi and Salmonella Paratyphi A in Healthy Adults 18 to 50 Years of Age in Europe
Overview
- Phase
- Phase 1
- Intervention
- TYP04A Low Dose without Alum investigational vaccine
- Conditions
- Typhoid Fever
- Sponsor
- GlaxoSmithKline
- Enrollment
- 97
- Locations
- 1
- Primary Endpoint
- Number of Participants With Solicited Administration-site Events After the First Vaccination
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants who, in the opinion of the Investigator, can and will comply with the requirements of the Protocol (e.g., completion of the diary cards, return for follow-up visits).
- •Written informed consent obtained from the participant prior to performance of any study specific procedure.
- •Healthy participants as established by medical history, clinical examination, and screening laboratory investigations.
- •Participant satisfying screening requirements.
- •Participant seronegative for human immunodeficiency virus, hepatitis B, and hepatitis C at Screening.
- •A male or female participant between, and including, 18 and 50 years of age at the time of the first study intervention administration.
- •Female participants of non-childbearing potential may be enrolled in the study. Non-childbearing 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 study 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
Exclusion Criteria
- •Medical conditions
- •Progressive, unstable or uncontrolled clinical conditions.
- •History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
- •Hypersensitivity, including allergy, to medicinal products or medical equipment whose use is foreseen in this study.
- •Clinical conditions representing a contraindication to intramuscular vaccination and blood draws.
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
- •Any behavioural 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.
- •Acute\* or chronic illness, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by physical examination or laboratory screening tests.
- •\*Participants with a minor illness (such as mild diarrhoea or mild upper respiratory infection) without fever may be enrolled at the discretion of the Investigator.
- •Any clinically significant\* haematological and/or biochemical laboratory abnormality.
Arms & Interventions
Step 1a: Low dose TYP04A vaccine without Alum
Participants received low dose of the TYP04A vaccine without Alum intramuscularly on Day 1 and Day 169.
Intervention: TYP04A Low Dose without Alum investigational vaccine
Step 1b: Low dose TYP03A vaccine with Alum
Participants received low dose of the TYP03A vaccine with Alum intramuscularly on Day 1 and Day 169.
Intervention: TYP03A Low Dose with Alum investigational vaccine
Step 2: Full dose TYP04B vaccine without Alum
Participants received full dose of the TYP04B vaccine without Alum intramuscularly on Day 1 and day 169.
Intervention: TYP04B Full Dose without Alum investigational vaccine
Step 2: Full dose TYP03B vaccine with Alum
Participants received full dose of the TYP03B vaccine with Alum intramuscularly on Day 1 and day 169.
Intervention: TYP03B Full Dose with Alum investigational vaccine
Control: TYPHIM VI and BOOSTRIX vaccine
Participants received TYPHIM VI as comparator intramuscularly on Day 1, and BOOSTRIX as comparator on Day 169.
Intervention: Sanofi Pasteur's Typhoid Vi polysaccharide vaccine
Control: TYPHIM VI and BOOSTRIX vaccine
Participants received TYPHIM VI as comparator intramuscularly on Day 1, and BOOSTRIX as comparator on Day 169.
Intervention: GSK's Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine
Outcomes
Primary Outcomes
Number of Participants With Solicited Administration-site Events After the First Vaccination
Time Frame: From Day 1 to Day 7
Solicited administration site events included pain, redness, and swelling.
Number of Participants With Solicited Systemic Events After the First Vaccination
Time Frame: From Day 1 to Day 7
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).
Number of Participants With Solicited Administration-site Events After the Second Vaccination
Time Frame: From Day 169 to Day 175
Solicited administration site events included pain, redness, and swelling.
Number of Participants With Solicited Systemic Events After the Second Vaccination
Time Frame: From Day 169 to Day 175
The solicited systemic events included arthralgia (joint pain), fatigue (tiredness), fever, headache, and myalgia (muscle pain).
Number of Participants With Unsolicited Adverse Events (AEs) After the First Vaccination
Time Frame: From Day 1 to Day 28
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.
Number of Participants With Unsolicited Adverse Events After the Second Vaccination
Time Frame: From Day 169 to Day 196
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.
Number of Participants With Any Serious Adverse Events (SAEs)
Time Frame: From Day 1 to Day 197
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.
Number of Participants With AEs/SAEs Leading to Withdrawal From the Study
Time Frame: From Day 1 to Day 197
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.
Number of Participants With SAEs Leading to Withholding Further Study Intervention Administration
Time Frame: From Day 1 to Day 197
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.
Number of Participants With AEs Leading to Withholding Further Study Intervention Administration
Time Frame: From Day 1 to Day 197
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.
Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 8
Time Frame: At Day 8 compared to Day 1 (Baseline)
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.
Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 176
Time Frame: At Day 176 compared to Day 169 (Baseline)
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.
Secondary Outcomes
- Number of Participants With Anti-Vi Antigen IgG Antibody Concentrations Greater Than or Equal to (>=) 4.3 Micrograms Per Milliliter (µg/mL)(At Day 1, Day 29, Day 169, Day 176 and Day 197)
- Number of Participants With AEs/SAEs Leading to Withdrawal From the Study(From Day 197 to Day 337)
- Number of Participants With Any SAE(From Day 197 to Day 337)
- GMC of Anti-O:2 IgG Antibody Concentrations(At Day 1 (pre-dose 1), Day 29, Day 169 (pre-dose 2), Day 176 and Day 197)
- Geometric Mean Concentrations (GMCs) of Anti-Vi Antigen Immunoglobulin G (IgG) Antibody Concentrations(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(At Day 29, Day 169, Day 176, and Day 197 compared to Day 1 (baseline))
- GMR for Anti-Vi Antigen IgG Antibody Concentrations(At Day 176 and Day 197 compared to Day 169 (baseline))
- GMR for Anti-O:2 IgG Antibody Concentrations(At Day 176 and Day 197 compared to Day 169 (baseline))
- Number of Participants With Anti-Vi Antigen IgG Antibody Concentrations >= 2.0 µg/mL(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(At Day 29, Day 169, Day 176 and Day 197 compared to Day 1 (baseline))