Safety and Immunogenicity of a Novel Conjugate Vaccine Against Salmonella Typhi and Salmonella Paratyphi A in Healthy Adults

NCT05613205 | Completed Phase 1 Results

• 2 other identifiers: 2054802021-002029-19
• Study Type: interventional
• Target: 97
• Locations: 1 country
• Sites: 1

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.

Conditions

Typhoid Fever

Keywords

Salmonella Typhi; Salmonella Paratyphi A; Typhoid fever; Paratyphoid fever; Enteric fever; Conjugate vaccine; First-time-in-human

Outcome Measures

Primary Outcomes (12)

• Number of Participants With Solicited Administration-site Events After the First Vaccination

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

  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.

  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).

  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).

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  At Day 176 compared to Day 169 (Baseline)

Secondary Outcomes (11)

• Number of Participants With Any SAE

  From Day 197 to Day 337

• Number of Participants With AEs/SAEs Leading to Withdrawal From the Study

  From Day 197 to Day 337

• 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)

Study Arms (5)

Step 1a: Low dose TYP04A vaccine without Alum

EXPERIMENTAL

Participants received low dose of the TYP04A vaccine without Alum intramuscularly on Day 1 and Day 169.

Biological: TYP04A Low Dose without Alum investigational vaccine

Step 1b: Low dose TYP03A vaccine with Alum

EXPERIMENTAL

Participants received low dose of the TYP03A vaccine with Alum intramuscularly on Day 1 and Day 169.

Biological: TYP03A Low Dose with Alum investigational vaccine

Step 2: Full dose TYP04B vaccine without Alum

EXPERIMENTAL

Participants received full dose of the TYP04B vaccine without Alum intramuscularly on Day 1 and day 169.

Biological: TYP04B Full Dose without Alum investigational vaccine

Step 2: Full dose TYP03B vaccine with Alum

EXPERIMENTAL

Participants received full dose of the TYP03B vaccine with Alum intramuscularly on Day 1 and day 169.

Biological: TYP03B Full Dose with Alum investigational vaccine

Control: TYPHIM VI and BOOSTRIX vaccine

ACTIVE COMPARATOR

Participants received TYPHIM VI as comparator intramuscularly on Day 1, and BOOSTRIX as comparator on Day 169.

Biological: Sanofi Pasteur's Typhoid Vi polysaccharide vaccine; Biological: GSK's Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine

Interventions

TYP04A Low Dose without Alum investigational vaccine BIOLOGICAL

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.

Also known as: Typhoid and Paratyphoid A conjugate low dose without adjuvant vaccine

Step 1a: Low dose TYP04A vaccine without Alum

TYP04B Full Dose without Alum investigational vaccine BIOLOGICAL

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.

Also known as: Typhoid and Paratyphoid A conjugate full dose without adjuvant vaccine

Step 2: Full dose TYP04B vaccine without Alum

TYP03A Low Dose with Alum investigational vaccine BIOLOGICAL

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.

Also known as: Adjuvanted Typhoid and Paratyphoid A conjugate low dose vaccine

Step 1b: Low dose TYP03A vaccine with Alum

TYP03B Full Dose with Alum investigational vaccine BIOLOGICAL

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.

Also known as: Adjuvanted Typhoid and Paratyphoid A conjugate full dose vaccine

Step 2: Full dose TYP03B vaccine with Alum

Sanofi Pasteur's Typhoid Vi polysaccharide vaccine BIOLOGICAL

1 dose of Sanofi Pasteur's Typhoid Vi polysaccharide vaccine administered intramuscularly, at Day 1, to participants in the control group.

Also known as: TYPHIM VI

Control: TYPHIM VI and BOOSTRIX vaccine

GSK's Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine BIOLOGICAL

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.

Also known as: BOOSTRIX

Control: TYPHIM VI and BOOSTRIX vaccine

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• has agreed to continue adequate contraception during the entire treatment period and for 1 month after completion of the study intervention administration series.

You may not qualify if:

• 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.
• \*The Investigator should use his/her clinical judgement to decide which abnormalities are clinically significant.
• Confirmed positive COVID-19 test during the period starting 14 days before the first administration of study vaccines (Day -14 to Day 1).
• Any other clinical condition that, in the opinion of the Investigator, might pose additional risk to the participant due to participation in the study.
• Confirmed or suspected autoimmune diseases (e.g., vitiligo, autoimmune thyroiditis).
• Prior/Concomitant therapy

Sponsors & Collaborators

• GlaxoSmithKline: lead
• Biological E. Limited: collaborator

Study Sites (1)

GSK Investigational Site

Edegem, 2610, Belgium

Location

Related Publications (1)

• De Coster I, AbdelGhany M, Sarakinou E, Fineschi C, Marchetti E, La Gaetana R, Nigro S, Carducci M, Massai L, Conti V, Rossi O, Luna Cilio G, Serry-Bangura A, Tessitore P, Van Damme P, Withanage K, Micoli F, Berlanda Scorza F, Rondini S, Nakakana UN, Kumar Arora A. Safety and immunogenicity of a conjugate vaccine candidate against Salmonella enterica serovars Typhi and Paratyphi A in healthy adults in Europe: a phase 1 randomised controlled trial. Lancet Infect Dis. 2026 Jan 23:S1473-3099(25)00730-3. doi: 10.1016/S1473-3099(25)00730-3. Online ahead of print.

  PMID: 41587557 DERIVED

MeSH Terms

Conditions

Typhoid Fever; Paratyphoid Fever

Interventions

Adjuvants, Vaccine; Vaccines; Vi polysaccharide vaccine, typhoid; Boostrix

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Adjuvants, Pharmaceutic; Pharmaceutic Aids; Pharmaceutical Preparations; Adjuvants, Immunologic; Immunologic Factors; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Specialty Uses of Chemicals; Biological Products; Complex Mixtures

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Data will be collected in an observer-blind (Day 1 to Day 29) and in a Single-blind (Day 29 to Day 337) manner with participants and investigator blinded.
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2022
• First Posted: November 14, 2022
• Study Start: November 28, 2022
• Primary Completion: December 6, 2023
• Study Completion: April 2, 2024
• Last Updated: January 24, 2025
• Results First Posted: January 24, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, a key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the 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 can be granted, when justified, for up to another 12 months.

Locations

BE (1)