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

Phase 1

Completed

• Conditions: Typhoid Fever
• Interventions: Biological: TYP04A Low Dose without Alum investigational vaccine; Biological: TYP04B Full Dose without Alum investigational vaccine; Biological: TYP03A Low Dose with Alum investigational vaccine; Biological: Sanofi Pasteur's Typhoid Vi polysaccharide vaccine; Biological: TYP03B Full Dose with Alum investigational vaccine; Biological: TYP03A Low Dose adjuvanted investigational vaccine; Biological: TYP03B Full Dose adjuvanted investigational vaccine; Biological: TYP04A Low Dose without adjuvant investigational vaccine; Biological: TYP04B Full Dose without adjuvant investigational vaccine; Biological: GSK's Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine

• Registration Number: NCT05613205
• Lead Sponsor: GlaxoSmithKline

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-11-04
• Study First Submitted QC: 2022-11-04
• Study First Posted: 2022-11-14
• Study Start: 2022-11-28
• Primary Completion: 2023-12-06
• Study Completion: 2024-04-02
• Status Verified: 2024-12
• Results First Submitted: 2024-12-04
• Results First Submitted QC: 2024-12-04
• Last Update Submitted: 2024-12-04
• Results First Posted: 2025-01-24
• Last Update Posted: 2025-01-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 97

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

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.

  *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

• Previous administration of any type of Typhoid vaccine (Ty21a, Vi-PS, or Typhoid conjugate vaccine).

• Use of any investigational or non-registered product (drug, vaccine, or medical device) other than the study interventions during the period starting 30 days before the first administration of study vaccines (Day -30 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 (-21 days in the case of live vaccines) and ending 28 days after the last dose of study intervention administration*, with the exception of flu and COVID-19 vaccines, administered during the period starting at 7 days before and 7 days after each dose (14 days before and 14 days after in case of live vaccines).

  *In case emergency mass vaccination for an unforeseen public health threat (e.g., a pandemic) is recommended and/or organised by public health authorities outside the routine immunisation programme, the time period described above can be reduced if, necessary for that vaccine, provided it is used according to the local governmental recommendations and that the Sponsor is notified accordingly. When regulations allow, the recommended time intervals for administration of these vaccines are at least 7 days before or 7 days after (at least 14 days before or 14 days after in case of live vaccines) each dose of study intervention administration.

• Administration of long-acting immune-modifying drugs at any time during the study period (e.g., infliximab).

• Administration of immunoglobulins and/or any blood products or plasma derivatives during the period starting 3 months before the administration of the first dose of study intervention or planned administration during the study period.

• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first study intervention dose. For corticosteroids, this will mean prednisone equivalent ≥20 mg/day for adult participants. Inhaled and topical steroids are allowed.

Prior/Concurrent clinical study experience • Concurrently participating in another 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 vaccine/product (drug/invasive medical device).

Other exclusions

• History of travel to countries of Asia that are considered endemic* for enteric fever in the last 3 years.

  *this also includes travel during study duration.

• Pregnant or lactating female.

• Female participants planning to become pregnant or planning to discontinue contraceptive precautions.

• History of or current chronic alcohol consumption and/or drug abuse.

• Any study personnel or immediate dependents, family, or household member.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Step 1a: Low dose TYP04A vaccine without Alum	TYP04A Low Dose without Alum investigational vaccine	Participants received low dose of the TYP04A vaccine without Alum intramuscularly on Day 1 and Day 169.
Step 2: Full dose TYP04B vaccine without Alum	TYP04B Full Dose without Alum investigational vaccine	Participants received full dose of the TYP04B vaccine without Alum intramuscularly on Day 1 and day 169.
Step 1b: Low dose TYP03A vaccine with Alum	TYP03A Low Dose with Alum investigational vaccine	Participants received low dose of the TYP03A vaccine with Alum intramuscularly on Day 1 and Day 169.
Control: TYPHIM VI and BOOSTRIX vaccine	Sanofi Pasteur's Typhoid Vi polysaccharide vaccine	Participants received TYPHIM VI as comparator intramuscularly on Day 1, and BOOSTRIX as comparator on Day 169.
Step 2: Full dose TYP03B vaccine with Alum	TYP03B Full Dose with Alum investigational vaccine	Participants received full dose of the TYP03B vaccine with Alum intramuscularly on Day 1 and day 169.
Control: TYPHIM VI and BOOSTRIX vaccine	GSK's Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine	Participants received TYPHIM VI as comparator intramuscularly on Day 1, and BOOSTRIX as comparator on Day 169.
Step 1b low dose with adjuvant Group	TYP03A Low Dose adjuvanted investigational vaccine	Participants 18 to 50 years of age randomized to receive 2 doses of TYP03A Low Dose adjuvanted investigational vaccine, administered at Day 1 and Day 169.
Step 2 full dose with adjuvant Group	TYP03B Full Dose adjuvanted investigational vaccine	Participants 18 to 50 years of age randomized to receive 2 doses of TYP03B Full Dose adjuvanted investigational vaccine, administered at Day 1 and Day 169.
Step 2 control Group	Sanofi Pasteur's Typhoid Vi polysaccharide vaccine	Participants 18 to 50 years of age randomized to receive 1 dose of Sanofi Pasteur's Typhoid Vi polysaccharide vaccine at Day 1 and 1 dose of GSK's Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine at Day 169.
Step 1a control Group	GSK's Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine	Participants 18 to 50 years of age randomized to receive 1 dose of Sanofi Pasteur's Typhoid Vi polysaccharide vaccine at Day 1 and 1 dose of GSK's Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine at Day 169.
Step 1a low dose without adjuvant Group	TYP04A Low Dose without adjuvant investigational vaccine	Participants 18 to 50 years of age randomized to receive 2 doses of TYP04A Low Dose without adjuvant investigational vaccine, administered at Day 1 and Day 169.
Step 1b control Group	Sanofi Pasteur's Typhoid Vi polysaccharide vaccine	Participants 18 to 50 years of age randomized to receive 1 dose of Sanofi Pasteur's Typhoid Vi polysaccharide vaccine at Day 1 and 1 dose of GSK's Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine at Day 169.
Step 2 full dose without adjuvant Group	TYP04B Full Dose without adjuvant investigational vaccine	Participants 18 to 50 years of age randomized to receive 2 doses of TYP04B Full Dose without adjuvant investigational vaccine, administered at Day 1 and Day 169.
Step 1a control Group	Sanofi Pasteur's Typhoid Vi polysaccharide vaccine	Participants 18 to 50 years of age randomized to receive 1 dose of Sanofi Pasteur's Typhoid Vi polysaccharide vaccine at Day 1 and 1 dose of GSK's Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine at Day 169.
Step 1b control Group	GSK's Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine	Participants 18 to 50 years of age randomized to receive 1 dose of Sanofi Pasteur's Typhoid Vi polysaccharide vaccine at Day 1 and 1 dose of GSK's Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine at Day 169.
Step 2 control Group	GSK's Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine	Participants 18 to 50 years of age randomized to receive 1 dose of Sanofi Pasteur's Typhoid Vi polysaccharide vaccine at Day 1 and 1 dose of GSK's Tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine at Day 169.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Solicited Administration-site Events After the First Vaccination	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	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	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	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	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	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)	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	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	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	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	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	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 Outcome Measures

Name	Time	Method
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	Blood samples were collected at specified timepoint for each component as measured by ELISA.
Number of Participants With AEs/SAEs Leading to Withdrawal From the Study	From Day 197 to Day 337	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 Any SAE	From Day 197 to Day 337	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.
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	Anti-O:2 IgG antibodies in serum were measured by an ELISA assay. Blood samples were collected at specified timepoints.
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	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.
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)	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.
GMR for Anti-Vi Antigen IgG Antibody Concentrations	At Day 176 and Day 197 compared to Day 169 (baseline)	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.
GMR for Anti-O:2 IgG Antibody Concentrations	At Day 176 and Day 197 compared to Day 169 (baseline)	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.
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	Blood samples were collected at specified timepoint for each component as measured by ELISA.
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)	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.

Trial Locations

Locations (1)

GSK Investigational Site; 🇧🇪 Edegem, Belgium