Clinical trial NCT05613205: Safety and Immunogenicity of a Novel Conjugate Vaccine Against Salmonella Typhi and Salmonella Paratyphi A in Healthy Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Typhoid Fever
Keywords: Salmonella Typhi
Salmonella Paratyphi A
Typhoid fever
Paratyphoid fever
Enteric fever
Conjugate vaccine
First-time-in-human
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Biological E. Limited
First posted: 2022-11-14
Enrollment: 97
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

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.


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
  * 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.

Primary outcomes:
measure: Number of Participants With Solicited Administration-site Events After the First Vaccination
timeFrame: From Day 1 to Day 7
measure: Number of Participants With Solicited Administration-site Events After the Second Vaccination
timeFrame: From Day 169 to Day 175
measure: Number of Participants With Solicited Systemic Events After the First Vaccination
timeFrame: From Day 1 to Day 7
measure: Number of Participants With Solicited Systemic Events After the Second Vaccination
timeFrame: From Day 169 to Day 175
measure: Number of Participants With Unsolicited Adverse Events (AEs) After the First Vaccination
timeFrame: From Day 1 to Day 28
measure: Number of Participants With Unsolicited Adverse Events After the Second Vaccination
timeFrame: From Day 169 to Day 196
measure: Number of Participants With Any Serious Adverse Events (SAEs)
timeFrame: From Day 1 to Day 197
measure: Number of Participants With AEs/SAEs Leading to Withdrawal From the Study
timeFrame: From Day 1 to Day 197
measure: Number of Participants With SAEs Leading to Withholding Further Study Intervention Administration
timeFrame: From Day 1 to Day 197
measure: Number of Participants With AEs Leading to Withholding Further Study Intervention Administration
timeFrame: From Day 1 to Day 197
measure: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 8
timeFrame: At Day 8 compared to Day 1 (Baseline)
measure: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 176
timeFrame: At Day 176 compared to Day 169 (Baseline)
Secondary outcomes:
measure: Number of Participants With Any SAE
timeFrame: From Day 197 to Day 337
measure: Number of Participants With AEs/SAEs Leading to Withdrawal From the Study
timeFrame: From Day 197 to Day 337
measure: Geometric Mean Concentrations (GMCs) of Anti-Vi Antigen Immunoglobulin G (IgG) Antibody Concentrations
timeFrame: At Day 1 (pre-dose 1), Day 29, Day 169 (pre-Dose 2), Day 176 and Day 197
measure: Geometric Mean Ratio (GMR) for Anti-Vi Antigen IgG Antibody Concentrations
timeFrame: At Day 29, Day 169, Day 176, and Day 197 compared to Day 1 (baseline)
measure: GMR for Anti-Vi Antigen IgG Antibody Concentrations
timeFrame: At Day 176 and Day 197 compared to Day 169 (baseline)
measure: GMC of Anti-O:2 IgG Antibody Concentrations
timeFrame: At Day 1 (pre-dose 1), Day 29, Day 169 (pre-dose 2), Day 176 and Day 197
measure: GMR for Anti-O:2 IgG Antibody Concentrations
timeFrame: At Day 29, Day 169, Day 176, and Day 197 compared to Day 1 (baseline)
measure: GMR for Anti-O:2 IgG Antibody Concentrations
timeFrame: At Day 176 and Day 197 compared to Day 169 (baseline)
measure: Number of Participants With Anti-Vi Antigen IgG Antibody Concentrations Greater Than or Equal to (>=) 4.3 Micrograms Per Milliliter (µg/mL)
timeFrame: At Day 1, Day 29, Day 169, Day 176 and Day 197
measure: Number of Participants With Anti-Vi Antigen IgG Antibody Concentrations >= 2.0 µg/mL
timeFrame: At Day 1, Day 29, Day 169, Day 176 and Day 197
measure: Number of Participants With at Least 4-fold Increase in Anti-O:2 IgG Antibody Concentrations
timeFrame: At Day 29, Day 169, Day 176 and Day 197 compared to Day 1 (baseline)
Other outcomes:
Locations:
city: Edegem
country: Belgium
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: