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Completed

NCT Number: NCT05480800

A Study to Evaluate Safety, Reactogenicity, and Immune Response of GVGH iNTS-TCV Vaccine Against Invasive Nontyphoidal Salmonella and Typhoid Fever

The purpose of this study is to assess the safety, reactogenicity, and immune response induced by the GlaxoSmithKline Biologicals SA (GSK) Vaccines Institute for Global Health (GVGH) invasive nontyphoidal Salmonella-typhoid conjugate (iNTS-TCV) candidate vaccine to be administered for the first time in humans. The study intervention will be evaluated in European adults in Stage 1 (a 2-step staggered design) followed by African adults in Stage 2.

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Key information

Conditions

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

Age range

18 year–50 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

GSK Investigational Site, Edegem, Belgium

Loading trial locations.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participants, who, in the opinion of the Investigator, can and will comply with the requirements of the protocol.
  • Written or witnessed/thumb printed informed consent obtained from the participant prior to performance of any study-specific procedure.
  • Healthy participants as established by medical history, clinical examination, and laboratory assessment.
  • Participant satisfying screening requirements.
  • A male or female between and including 18 and 50 years of age at the time of the first study intervention administration.
  • Female participants of nonchildbearing potential may be enrolled in the study. Nonchildbearing 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 trial 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.
  • Blood sample for simultaneous follicle-stimulating hormone (FSH) and estradiol levels may be collected at the discretion of the Investigator to confirm non-reproductive potential according to local laboratory reference range.
  • Genetic testing for HLA-B27 will be performed at Screening and only participants with a negative result will be allowed to participate in the study*.
  • Only for Stage 1.
  • For Malawi (Stage 2), the participant lives in Blantyre and has agreed to remain in Blantyre for the study duration.

Exclusion criteria

Medical Conditions

  • Known exposure to S. Typhi and nontyphoidal Salmonella confirmed by blood culture during the period starting 3 years prior to first study intervention administration confirmed using past medical history.
  • History of any reaction or hypersensitivity associated with any component of the study interventions.
  • Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
  • Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by physical examination or laboratory screening tests.
  • Recurrent history or uncontrolled neurological disorders or seizures.
  • Any clinically significant* hematological and/or biochemical laboratory abnormality.
  • The Investigator should use his/her clinical judgment to decide which abnormalities are clinically significant from the panel of tests in the list of safety assays.
  • Clinical conditions representing a contraindication to IM injections and/or blood draws.
  • Any behavioral 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.
  • Confirmed positive COVID-19 polymerase chain reaction or lateral flow test during the period starting 28 days before the first administration of study vaccines (Day -28 to Day 1).
  • Acute or chronic illness which may be severe enough to preclude participation.
  • Any other clinical condition that, in the opinion of the Investigator, might pose additional risk to the participant due to participation in the study.
  • All medical conditions will be assessed by the Investigator who may use his/her discretion to decide if the participant meets the exclusion criteria.

Prior/Concomitant Therapy

  • History of receiving any typhoid vaccine (Ty21a, Vi capsular polysaccharide, or TCV) in the participant's life.
  • History of receiving any investigational iNTS or GMMA vaccines in the participant's life.
  • Use of any investigational or non-registered product other than the study interventions during the period beginning 30 days (Days -30 to 1) before the first dose of study interventions, or their 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 and ending 28 days after the last dose of study interventions administration*, with the exception of flu vaccines or COVID-19 vaccine.
  • In case emergency mass vaccination for an unforeseen public health threat (eg, a pandemic) is recommended and/or organized by public health authorities outside the routine immunization program, 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 (eg, infliximab).
  • Administration of Ig and/or any blood products or plasma derivatives during the period starting 3 months before the administration of the first dose of study interventions 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(s). 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 trial, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention (vaccine and drug).

Other Exclusions

  • Pregnant or lactating female
  • Female planning to become pregnant or planning to discontinue contraceptive precautions
  • History of/current chronic alcohol consumption and/or drug abuse. This will be decided at the discretion of the Investigator. Chronic alcohol consumption is defined as one or more of the following:
  • A prolonged period of frequent and heavy alcohol use
  • The inability to control drinking once it has begun
  • Physical dependence manifested by withdrawal symptoms when the individual stops using alcohol
  • Tolerance or the need to use increasing amounts of alcohol to achieve the same effects
  • A variety of social and/or legal problems arising from alcohol use.
  • Any study personnel or their immediate dependents, family, or household members.

Treatment and study plan

Invasive nontyphoidal Salmonella-typhoid conjugate vaccine (iNTS-TCV) low dose

Biological

3 doses of iNTS-TCV low dose vaccine administered intramuscularly at Day 1, Day 57, and Day 169 to participants in the iNTS-TCV low dose Group in Stage 1 (Europe).

Invasive nontyphoidal Salmonella-generalized modules for membrane antigens vaccine (iNTS-GMMA) low dose

Biological

3 doses of iNTS-GMMA low dose vaccine administered intramuscularly at Day 1, Day 57, and Day 169 to participants in the iNTS-GMMA and TCV low doses Group in Stage 1 (Europe).

Typhoid conjugate vaccine (TCV) low dose

Biological

3 doses of TCV low dose vaccine administered intramuscularly at Day 1, Day 57, and Day 169 to participants in the iNTS-GMMA and TCV low doses Group in Stage 1 (Europe).

Invasive nontyphoidal Salmonella-typhoid conjugate vaccine (iNTS-TCV) full dose

Biological

3 doses of iNTS-TCV full dose vaccine administered intramuscularly at Day 1, Day 57, and Day 169 to participants in the iNTS-TCV full dose Group in Stage 1 (Europe) and to participants in iNTS-TCV full dose Group in Stage 2 (Africa).

Invasive nontyphoidal Salmonella-generalized modules for membrane antigens vaccine (iNTS-GMMA) full dose

Biological

3 doses of iNTS-GMMA full dose vaccine administered intramuscularly at Day 1, Day 57, and Day 169 to participants in the iNTS-GMMA + TCV full dose Group in Stage 1 (Europe) and to participants in the iNTS-GMMA + TCV full dose Group in Stage 2 (Africa).

Typhoid conjugate vaccine (TCV) full dose

Biological

3 doses of TCV full dose vaccine administered intramuscularly at Day 1, Day 57, and Day 169 to participants in the iNTS-GMMA + TCV full dose Group in Stage 1 (Europe) and to participants in the iNTS-GMMA + TCV full dose Group in Stage 2 (Africa).

GSK's Meningococcal A, C, Y and W-135 conjugate vaccine

Biological

1 dose of GSK's Meningococcal A, C, Y and W-135 conjugate vaccine administered intramuscularly at Day 1 to participants in the Control Group in Stage 2 (Africa).

Other names: MENVEO

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

Combination Product

1 dose of GSK's Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine administered intramuscularly at Day 57 to participants in the Control Group in Stage 2 (Africa).

Other names: Boostrix

Sanofi Pasteur's Typhoid Vi polysaccharide vaccine

Combination Product

1 dose of Sanofi Pasteur's Typhoid Vi polysaccharide vaccine administered intramuscularly at Day 169 to participants in the Control Group in Stage 2 (Africa).

Other names: TYPHIM Vi

Placebo

Drug

3 doses of Placebo administered intramuscularly at Day 1, Day 57, and Day 169 to participants in the Placebo Group in Stage 1 (Europe).

Saline

Other

3 doses of saline solution administered intramuscularly at Day 1, Day 57, and Day 169 to the participants.

Primary outcomes

  1. Stage 1: Number of Participants With Any Solicited Administration Site Events After the First Study Intervention Administration

    Time frame: Within 7 days post vaccination (day of administration and 6 subsequent days post-first vaccination on Day 1)

    The solicited administration site events included redness (erythema), pain, and swelling. Data for solicited administration site events is presented for each intervention administered in each arm group. Any = occurrence of the event regardless of intensity grade.

  2. Stage 1: Number of Participants With Any Solicited Administration Site Events After the Second Study Intervention Administration

    Time frame: Within 7 days post vaccination (day of administration and 6 subsequent days post-second vaccination on Day 57)

    The solicited administration site events included redness (Erythema), pain and swelling. Data for solicited administration site events is presented for each intervention administered in each arm group. Any = occurrence of the event regardless of intensity grade.

  3. Stage 1: Number of Participants With Any Solicited Administration Site Events After the Third Study Intervention Administration

    Time frame: Within 7 days post vaccination (day of administration and 6 subsequent days post-third vaccination on Day 169)

    The solicited administration site events included redness (Erythema), pain and swelling. Data for solicited administration site events is presented for each intervention administered in each arm group. Any = occurrence of the event regardless of intensity grade.

  4. Stage 1: Number of Participants With Any Solicited Systemic Events After the First Study Intervention Administration

    Time frame: Within 7 days post vaccination (day of administration and 6 subsequent days post-first vaccination on Day 1)

    The solicited systemic events included arthralgia (joint pain), fatigue (tiredness), headache, myalgia (muscle pain) and fever (pyrexia). Fever is defined as body temperature equal to or above (>=) 38.0 degrees Celsius (°C). The preferred location for measuring temperature is the axilla. Any = occurrence of the event regardless of intensity grade.

  5. Stage 1: Number of Participants With Any Solicited Systemic Events After the Second Study Intervention Administration

    Time frame: Within 7 days post vaccination (day of administration and 6 subsequent days post-second vaccination on Day 57)

    The solicited systemic events included arthralgia (joint pain), fatigue (tiredness), headache, myalgia (muscle pain) and fever (pyrexia). Fever is defined as body temperature equal to or above (≥) 38.0 degrees Celsius (°C). The preferred location for measuring temperature is the axilla. Any = occurrence of the event regardless of intensity grade.

  6. Stage 1: Number of Participants With Any Solicited Systemic Events After the Third Study Intervention Administration

    Time frame: Within 7 days post vaccination (day of administration and 6 subsequent days post-third vaccination on Day 169)

    The solicited systemic events included arthralgia (joint pain), fatigue (tiredness), headache, myalgia (muscle pain) and fever (pyrexia). Fever is defined as body temperature equal to or above (≥) 38.0 degrees Celsius (°C). The preferred location for measuring temperature is the axilla. Any = occurrence of the event regardless of intensity grade.

  7. Stage 1: Number of Participants With Any Unsolicited Adverse Events (AE) After the First Study Intervention Administration

    Time frame: Within 28 days post vaccination (day of administration and 27 subsequent days post-first vaccination on Day 1)

    An unsolicited AE is an AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited AE. Any = occurrence of the event regardless of intensity grade.

  8. Stage 1: Number of Participants With Any Unsolicited AEs After the Second Study Intervention Administration

    Time frame: Within 28 days post vaccination (day of administration and 27 subsequent days post-second vaccination on Day 57)

    An unsolicited AE is an AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited AE. Any = occurrence of the event regardless of intensity grade.

  9. Stage 1: Number of Participants With Any Unsolicited AEs After the Third Study Intervention Administration

    Time frame: Within 28 days post vaccination (day of administration and 27 subsequent days post-third vaccination on Day 169)

    An unsolicited AE is an AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited AE. Any = occurrence of the event regardless of intensity grade.

  10. Stage 1: Number of Participants With Any Serious Adverse Events (SAEs)

    Time frame: From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (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. Any = occurrence of the event regardless of intensity grade.

  11. Stage 1: Number of Participants With Any AEs/SAEs Leading to Withdrawal From the Study

    Time frame: From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (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. 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. 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. Any = occurrence of the event regardless of intensity grade.

  12. Stage 1: Number of Participants With Any AEs/SAEs Leading to Withholding Further Study Intervention Administration

    Time frame: From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (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.

    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/SAEs that lead to withholding of the study intervention administration were considered under this outcome measure. Any = occurrence of the event regardless of intensity grade.

  13. Stage 1: 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 (7 days after the first study intervention administration) compared to Baseline (Day 1)

    Assessed hepatic laboratory parameters included alanine aminotransferase [ALT] and aspartate aminotransferase [AST], and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 1 (baseline) and Day 8 hematological, renal and hepatic laboratory results are defined as follows: <range> (at baseline) - <range> (at timing) (e.g. Within (Baseline) - Within (Day 8)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  14. Stage 1: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 64

    Time frame: At Day 64 (7 days after the second study intervention administration) compared to Baseline (Day 57)

    Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 57 (baseline) and Day 64 hematological, renal and hepatic laboratory results are defined as follows: <range> (at baseline) - <range> (at timing) (e.g. Within (Baseline) - Within (Day 64)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  15. Stage 1: 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 (7 days after the third study intervention administration) compared to Baseline (Day 169)

    Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 169 (baseline) and Day 176 hematological, renal and hepatic laboratory results are defined as follows: <range> (at baseline) - <range> (at timing) (e.g. Within (Baseline) - Within (Day 176)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  16. Stage 1: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 29

    Time frame: At Day 29 (28 days after the first study intervention administration) compared to Baseline (Day 1)

    Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 1 (baseline) and Day 29 hematological, renal and hepatic laboratory results are defined as follows: <range> (at baseline) - <range> (at timing) (e.g. Within (Baseline) - Within (Day 29)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  17. Stage 1: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 85

    Time frame: At Day 85 (28 days after the second study intervention administration) compared to Baseline (Day 57)

    Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 57 (baseline) and Day 85 hematological, renal and hepatic laboratory results are defined as follows: <range> (at baseline) - <range> (at timing) (e.g. Within (Baseline) - Within (Day 85)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  18. Stage 1: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 197

    Time frame: At Day 197 (28 days after the third study intervention administration) compared to Baseline (Day 169)

    Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 169 (baseline) and Day 197 hematological, renal and hepatic laboratory results are defined as follows: <range> (at baseline) - <range> (at timing) (e.g. Within (Baseline) - Within (Day 197)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  19. Stage 2: Number of Participants With Any Solicited Administration Site Events After the First Study Intervention Administration

    Time frame: Within 7 days post vaccination (day of administration and 6 subsequent days post-first vaccination on Day 1)

    The solicited administration site events included redness (Erythema), pain and swelling. Data for solicited administration site events is presented for each intervention administered in each arm group. Any = occurrence of the event regardless of intensity grade.

  20. Stage 2: Number of Participants With Any Solicited Administration Site Events After the Second Study Intervention Administration

    Time frame: Within 7 days post vaccination (day of administration and 6 subsequent days post-second vaccination on Day 57)

    The solicited administration site events included redness (Erythema), pain and swelling. Data for solicited administration site events is presented for each intervention administered in each arm group. Any = occurrence of the event regardless of intensity grade.

  21. Stage 2: Number of Participants With Any Solicited Administration Site Events After the Third Study Intervention Administration

    Time frame: Within 7 days post vaccination (day of administration and 6 subsequent days post-third vaccination on Day 169)

    The solicited administration site events included redness (Erythema), pain and swelling. Data for solicited administration site events is presented for each intervention administered in each arm group. Any = occurrence of the event regardless of intensity grade.

  22. Stage 2: Number of Participants With Any Solicited Systemic Events After the First Study Intervention Administration

    Time frame: Within 7 days post vaccination (day of administration and 6 subsequent days post-first vaccination on Day 1)

    The solicited systemic events included arthralgia (joint pain), fatigue (tiredness), headache, myalgia (muscle pain) and fever (pyrexia). Fever is defined as body temperature >=38.0 degrees Celsius (°C). The preferred location for measuring temperature is the axilla. Any = occurrence of the event regardless of intensity grade.

  23. Stage 2: Number of Participants With Solicited Systemic Events After the Second Study Intervention Administration

    Time frame: Within 7 days post vaccination (day of administration and 6 subsequent days post-second vaccination on Day 57)

    The solicited systemic events included arthralgia (joint pain), fatigue (tiredness), headache, myalgia (muscle pain) and fever (pyrexia). Fever is defined as body temperature >=38.0 degrees Celsius (°C). The preferred location for measuring temperature is the axilla. Any = occurrence of the event regardless of intensity grade.

  24. Stage 2: Number of Participants With Any Solicited Systemic Events After the Third Study Intervention Administration

    Time frame: Within 7 days post vaccination (day of administration and 6 subsequent days post-third vaccination on Day 169)

    The solicited systemic events included arthralgia (joint pain), fatigue (tiredness), headache, myalgia (muscle pain) and fever (pyrexia). Fever is defined as body temperature >=38.0 degrees Celsius (°C). The preferred location for measuring temperature is the axilla. Any = occurrence of the event regardless of intensity grade.

  25. Stage 2: Number of Participants With Any Unsolicited AE After the First Study Intervention Administration

    Time frame: Within 28 days post vaccination (day of administration and 27 subsequent days post-first vaccination on Day 1)

    An unsolicited AE is an AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited AE. Any = occurrence of the event regardless of intensity grade.

  26. Stage 2: Number of Participants With Any Unsolicited AE After the Second Study Intervention Administration

    Time frame: Within 28 days post vaccination (day of administration and 27 subsequent days post-second vaccination on Day 57)

    An unsolicited AE is an AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited AE. Any = occurrence of the event regardless of intensity grade.

  27. Stage 2: Number of Participants With Any Unsolicited AE After the Third Study Intervention Administration

    Time frame: Within 28 days post vaccination (day of administration and 27 subsequent days post-third vaccination on Day 169)

    An unsolicited AE is an AE reported in addition to those solicited during the clinical study. Also, any 'solicited' symptom with onset outside the specified period of follow-up for solicited symptoms is reported as an unsolicited AE. Any = occurrence of the event regardless of intensity grade.

  28. Stage 2: Number of Participants With Any SAEs

    Time frame: From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (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. Any = occurrence of the event regardless of intensity grade.

  29. Stage 2: Number of Participants With Any AEs/SAEs Leading to Withdrawal From the Study

    Time frame: From first study intervention administration (Day 1) up to 28 days after the third study intervention (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. Any = occurrence of the event regardless of intensity grade.

  30. Stage 2: Number of Participants With Any AEs/SAEs Leading to Withholding Further Study Intervention Administration

    Time frame: From first study intervention administration (Day 1) up to 28 days after the third study intervention (Day 197)

    AEs/SAEs that lead to withholding of the study intervention administration were considered under this outcome measure. Any = occurrence of the event regardless of intensity grade.

  31. Stage 2: 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 (7 days after the first study intervention administration) compared to Baseline (Day 1)

    Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 1 (baseline) and Day 8 hematological, renal and hepatic laboratory results are defined as follows: <range> (at baseline) - <range> (at timing) (e.g. Within (Baseline) - Within (Day 8)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  32. Stage 2: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 64

    Time frame: At Day 64 (7 days after the second study intervention administration) compared to Baseline (Day 57)

    Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 57 (baseline) and Day 64 hematological, renal and hepatic laboratory results are defined as follows: <range> (at baseline) - <range> (at timing) (e.g. Within (Baseline) - Within (Day 64)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  33. Stage 2: 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 (7 days after the third study intervention administration) compared to Baseline (Day 169)

    Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 169 (baseline) and Day 176 hematological, renal and hepatic laboratory results are defined as follows: <range> (at baseline) - <range> (at timing) (e.g. Within (Baseline) - Within (Day 176)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  34. Stage 2: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 29

    Time frame: At Day 29 (28 days after the first study intervention administration) compared to Baseline (Day 1)

    Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 1 (baseline) and Day 29 hematological, renal and hepatic laboratory results are defined as follows: <range> (at baseline) - <range> (at timing) (e.g. Within (Baseline) - Within (Day 29)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  35. Stage 2: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 85

    Time frame: At Day 85 (28 days after the second study intervention administration) compared to Baseline (Day 57)

    Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 57 (baseline) and Day 85 hematological, renal and hepatic laboratory results are defined as follows: <range> (at baseline) - <range> (at timing) (e.g. Within (Baseline) - Within (Day 85)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

  36. Stage 2: Number of Participants With Deviations From Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test Results at Day 197

    Time frame: At Day 197 (28 days after the third study intervention administration) compared to Baseline (Day 169)

    Assessed hepatic laboratory parameters included ALT and AST, and renal laboratory parameters included creatinine and urea/blood urea nitrogen. Hematological laboratory parameters included basophils, eosinophils, hemoglobin, lymphocytes, monocytes, neutrophils, platelets and white blood cells (WBCs). Categories reported when comparing Day 169 (baseline) and Day 197 hematological, renal and hepatic laboratory results are defined as follows: <range> (at baseline) - <range> (at timing) (e.g. Within (Baseline) - Within (Day 197)) where range is being classified as below, within or above the normal range. Below = value below the laboratory reference range defined for the specified visit and laboratory parameter; Within = value within the laboratory reference range defined for the specified visit and laboratory parameter; Above = value above the laboratory reference range defined for the specified visit and laboratory parameter.

Secondary outcomes

  1. Stage 1 and Stage 2: Number of Participants With Any SAEs

    Time frame: From 28 days after the third study intervention administration (Day 197) up to study end (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. Any = occurrence of the event regardless of intensity grade.

  2. Stage 1 and Stage 2: Number of Participants With Any AEs/SAEs Leading to Withdrawal From the Study

    Time frame: From 28 days after the third study intervention administration (Day 197) up to study end (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. Any = occurrence of the event regardless of intensity grade.

  3. Stage 1: Geometric Mean Concentrations (GMCs) of Anti-serotype Specific Immunoglobulin G (IgG) in Participants and Between Group Ratios for Anti-Vi Antigen (Ag) Total IgG

    Time frame: At Days 1, 57, and 169 (before each study intervention administration) and at Days 29, 85, and 197 (28 days after each study intervention administration)

    Anti-Vi antigen (Ag) total IgG GMCs were assessed. Blood samples were collected at specified timepoint for each component as measured by Enzyme-Linked Immunosorbent Assay (ELISA). The lower limit of quantification (LLOQ) for antibody concentrations was >=2.2 microgram per milliliter (µg/mL). In case the measured antibody concentration fell below 2.2 µg/mL, a value of half the LLOQ value was imputed.

  4. Stage 1: GMCs of Anti-serotype Specific IgG in Participants and Between Group Ratios for Anti-S. Typhimurium OAg Total IgG and Anti-S. Enteritidis OAg Total IgG

    Time frame: At Days 1, 57, and 169 (before each study intervention administration) and at Days 29, 85, and 197 (28 days after each study intervention administration)

    Anti-S. Typhimurium OAg total IgG, Anti-S. Enteritidis OAg total IgG GMCs were assessed. Blood samples were collected at specified timepoint for each component as measured by Enzyme-Linked Immunosorbent Assay (ELISA).

  5. Stage 1: Geometric Mean Ratios (GMRs) for Anti-serotype Specific Immunoglobulin G (IgG) Concentrations

    Time frame: At 28 days after each study intervention administration compared to each study intervention administration baseline (Day 29 versus Day 1, Day 85 versus Day 57 and Day 197 versus Day 169)

    Anti-Vi antigen (Ag) total IgG, Anti-S. Typhimurium OAg total IgG, Anti-S. Enteritidis OAg total IgG within-participant GMRs were assessed. Blood samples were collected at specified timepoint for each component as measured by ELISA. Within participant GMRs were calculated as ratio of concentration in the post-vaccination timepoint to the pre-vaccination timepoint.

  6. Stage 1: Number of Participants Achieving at Least a 4 Fold Rise in Anti Serotype Specific Immunoglobulin G (IgG) Antibody Concentration for Each Antigen (Ag)

    Time frame: At Days 29, 85, and 197 (28 days after each study intervention administration) compared to Day 1 (first study intervention administration)

    Anti-Vi Ag total IgG, Anti-S. Typhimurium OAg total IgG, Anti-S. Enteritidis OAg total IgG antibody concentrations were assessed. Blood samples were collected at specified timepoint for each component as measured by ELISA.

  7. Stage 1: Number of Participants With Anti-Vi Ag IgG Antibody Concentrations Greater Than or Equal to (>=) 4.3 Micrograms Per Milliliter (µg/mL)

    Time frame: At Days 1, 57 and 169 (before each study intervention administration) and at Days 29, 85 and 197 (28 days after each study intervention administration)

    Blood samples were collected at specified timepoint for each component as measured by ELISA.

  8. Stage 2: GMCs of Anti-serotype Specific IgG in Participants and Between Group Ratios for Anti-Vi Ag Total IgG

    Time frame: At Days 1, 57, and 169 (before each study intervention administration) and at Days 29, 85, and 197 (28 days after each study intervention administration)

    Anti-Vi Ag total IgG GMCs and between group ratios were assessed. Blood samples were collected at specified timepoint for each component as measured by ELISA.

  9. Stage 2: GMCs of Anti-serotype Specific IgG in Participants and Between Group Ratios for Anti-S. Typhimurium OAg Total IgG and Anti-S. Enteritidis OAg Total IgG

    Time frame: At Days 1, 57, and 169 (before each study intervention administration) and at Days 29, 85, and 197 (28 days after each study intervention administration)

    Anti-S. Typhimurium OAg total IgG and Anti-S. Enteritidis OAg total IgG GMCs and between group ratios were assessed. Blood samples were collected at specified timepoint for each component as measured by ELISA.

  10. Stage 2: GMRs for Anti-serotype Specific Immunoglobulin G (IgG) Concentrations

    Time frame: At 28 days after each study intervention administration compared to each study intervention administration baseline (Day 29 versus Day 1, Day 85 versus Day 57 and Day 197 versus Day 169)

    Anti-Vi antigen (Ag) total IgG, Anti-S. Typhimurium OAg total IgG, Anti-S. Enteritidis OAg total IgG within-participant GMRs were assessed. Blood samples were collected at specified timepoint for each component as measured by ELISA. Within participant GMRs were calculated as ratio of concentration in the post-vaccination timepoint to the pre-vaccination timepoint.

  11. Stage 2: Number of Participants Achieving at Least a 4 Fold Rise in Anti Serotype Specific Immunoglobulin G (IgG) Antibody Concentration for Each Antigen (Ag)

    Time frame: At Days 29, 85, and 197 (28 days after each study intervention administration) compared to Day 1 (first study intervention administration baseline)

    Anti-Vi Ag total IgG, Anti-S. Typhimurium OAg total IgG, Anti-S. Enteritidis OAg total IgG antibody concentrations were assessed. Blood samples were collected at specified timepoint for each component as measured by ELISA.

  12. Stage 2: Number of Participants With Anti-Vi Ag IgG Antibody Concentrations >= 4.3 µg/mL

    Time frame: At Days 1, 57 and 169 (before each study intervention administration) and at Days 29, 85 and 197 (28 days after each study intervention administration)

    Blood samples were collected at specified timepoint for each component as measured by ELISA.

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Collaborators

  • Bill and Melinda Gates Foundation
  • Biomedical Advanced Research and Development Authority
  • Global Antimicrobial Resistance Innovation Fund-(GAMRIF)
  • Wellcome Trust

Registry information

Official study title

A Phase 1/2a, Observer-blind, Randomized, Controlled, Two-stage, Multi-country Study to Evaluate the Safety, Reactogenicity, and Immune Response of the Trivalent Vaccine Against Invasive Nontyphoidal Salmonella (iNTS) and Typhoid Fever in Healthy European and African Adults

Important dates

Study start
2022
Primary completion
2024
Study completion
2025
First posted
Jul 29, 2022
Registry last updated
Nov 28, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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