A study to evaluate safety, reactogenicity, and immune response of GVGH iNTS-TCV vaccine against invasive nontyphoidal Salmonella and Typhoid Fever
Trial overview
Stage 1: Number of Participants with any Solicited Administration Site Events after the First Study Intervention administration
Timeframe: Within 7 days post vaccination (day of administration and 6 subsequent days post-first vaccination on Day 1)
Stage 1: Number of Participants with any Solicited Administration Site Events after the Second Study Intervention administration
Timeframe: Within 7 days post vaccination (day of administration and 6 subsequent days post-second vaccination on Day 57)
Stage 1: Number of Participants with any Solicited Administration Site Events after the Third Study Intervention administration
Timeframe: Within 7 days post vaccination (day of administration and 6 subsequent days post-third vaccination on Day 169)
Stage 1: Number of Participants with any Solicited Systemic Events after the First Study Intervention administration
Timeframe: Within 7 days post vaccination (day of administration and 6 subsequent days post-first vaccination on Day 1)
Stage 1: Number of Participants with any Solicited Systemic Events after the Second Study Intervention administration
Timeframe: Within 7 days post vaccination (day of administration and 6 subsequent days post-second vaccination on Day 57)
Stage 1: Number of Participants with any Solicited Systemic Events after the Third Study Intervention administration
Timeframe: Within 7 days post vaccination (day of administration and 6 subsequent days post-third vaccination on Day 169)
Stage 1: Number of Participants with any Unsolicited adverse events (AE) after the First Study Intervention administration
Timeframe: Within 28 days post vaccination (day of administration and 27 subsequent days post-first vaccination on Day 1)
Stage 1: Number of Participants with any Unsolicited AEs after the Second Study Intervention administration
Timeframe: Within 28 days post vaccination (day of administration and 27 subsequent days post-second vaccination on Day 57)
Stage 1: Number of Participants with any Unsolicited AEs after the Third Study Intervention administration
Timeframe: Within 28 days post vaccination (day of administration and 27 subsequent days post-third vaccination on Day 169)
Stage 1: Number of Participants with any Serious Adverse Events (SAEs)
Timeframe: From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (Day 197)
Stage 1: Number of Participants with any AEs/SAEs Leading to Withdrawal from the Study
Timeframe: From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (Day 197)
Stage 1: Number of Participants with any AEs/SAEs Leading to Withholding Further Study Intervention Administration
Timeframe: From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (Day 197)
Stage 1: 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 (7 days after the first study intervention administration) compared to Baseline (Day 1)
Stage 1: Number of Participants with Deviations from Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 64
Timeframe: At Day 64 (7 days after the second study intervention administration) compared to Baseline (Day 57)
Stage 1: 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 (7 days after the third study intervention administration) compared to Baseline (Day 169)
Stage 1: Number of Participants with Deviations from Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 29
Timeframe: At Day 29 (28 days after the first study intervention administration) compared to Baseline (Day 1)
Stage 1: Number of Participants with Deviations from Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 85
Timeframe: At Day 85 (28 days after the second study intervention administration) compared to Baseline (Day 57)
Stage 1: Number of Participants with Deviations from Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 197
Timeframe: At Day 197 (28 days after the third study intervention administration) compared to Baseline (Day 169)
Stage 2: Number of Participants with any Solicited Administration Site Events after the First Study Intervention administration
Timeframe: Within 7 days post vaccination (day of administration and 6 subsequent days post-first vaccination on Day 1)
Stage 2: Number of Participants with any Solicited Administration Site Events after the Second Study Intervention administration
Timeframe: Within 7 days post vaccination (day of administration and 6 subsequent days post-second vaccination on Day 57)
Stage 2: Number of Participants with any Solicited Administration Site Events after the Third Study Intervention administration
Timeframe: Within 7 days post vaccination (day of administration and 6 subsequent days post-third vaccination on Day 169)
Stage 2: Number of Participants with any Solicited Systemic Events after the First Study Intervention administration
Timeframe: Within 7 days post vaccination (day of administration and 6 subsequent days post-first vaccination on Day 1)
Stage 2: Number of Participants with Solicited Systemic Events after the Second Study Intervention administration
Timeframe: Within 7 days post vaccination (day of administration and 6 subsequent days post-second vaccination on Day 57)
Stage 2: Number of Participants with any Solicited Systemic Events after the Third Study Intervention administration
Timeframe: Within 7 days post vaccination (day of administration and 6 subsequent days post-third vaccination on Day 169)
Stage 2: Number of Participants with any Unsolicited AE after the First Study Intervention administration
Timeframe: Within 28 days post vaccination (day of administration and 27 subsequent days post-first vaccination on Day 1)
Stage 2: Number of Participants with any Unsolicited AE after the Second Study Intervention administration
Timeframe: Within 28 days post vaccination (day of administration and 27 subsequent days post-second vaccination on Day 57)
Stage 2: Number of Participants with any Unsolicited AE after the Third Study Intervention administration
Timeframe: Within 28 days post vaccination (day of administration and 27 subsequent days post-third vaccination on Day 169)
Stage 2: Number of Participants with any SAEs
Timeframe: From first study intervention administration (Day 1) up to 28 days after the third study intervention administration (Day 197)
Stage 2: Number of Participants with any AEs/SAEs Leading to Withdrawal from the Study
Timeframe: From first study intervention administration (Day 1) up to 28 days after the third study intervention (Day 197)
Stage 2: Number of Participants with any AEs/SAEs Leading to Withholding Further Study Intervention Administration
Timeframe: From first study intervention administration (Day 1) up to 28 days after the third study intervention (Day 197)
Stage 2: 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 (7 days after the first study intervention administration) compared to Baseline (Day 1)
Stage 2: Number of Participants with Deviations from Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 64
Timeframe: At Day 64 (7 days after the second study intervention administration) compared to Baseline (Day 57)
Stage 2: 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 (7 days after the third study intervention administration) compared to Baseline (Day 169)
Stage 2: Number of Participants with Deviations from Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 29
Timeframe: At Day 29 (28 days after the first study intervention administration) compared to Baseline (Day 1)
Stage 2: Number of Participants with Deviations from Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 85
Timeframe: At Day 85 (28 days after the second study intervention administration) compared to Baseline (Day 57)
Stage 2: Number of Participants with Deviations from Normal or Baseline Values of Haematological, Renal, and Hepatic Panel Test results at Day 197
Timeframe: At Day 197 (28 days after the third study intervention administration) compared to Baseline (Day 169)
Stage 1 and Stage 2: Number of participants with any SAEs
Timeframe: From 28 days after the third study intervention administration (Day 197) up to study end (Day 337)
Stage 1 and Stage 2: Number of participants with any AEs/SAEs leading to withdrawal from the study
Timeframe: From 28 days after the third study intervention administration (Day 197) up to study end (Day 337)
Stage 1: Geometric mean concentrations (GMCs) of anti-serotype specific immunoglobulin G (IgG) in participants and between group ratios
Timeframe: 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)
Stage 1: Geometric mean ratios (GMRs) for anti-serotype specific immunoglobulin G (IgG) concentrations
Timeframe: 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)
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)
Timeframe: At Days 29, 85, and 197 (28 days after each study intervention administration) compared to Day 1 (first study intervention administration)
Stage 1: Number of participants with Anti-Vi Ag IgG antibody concentrations greater than or equal to (>=) 4.3 micrograms per milliliter (µg/mL)
Timeframe: 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)
Stage 2: GMCs of anti-serotype specific IgG in participants and between group ratios
Timeframe: 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)
Stage 2: GMRs for anti-serotype specific immunoglobulin G (IgG) concentrations
Timeframe: 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)
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)
Timeframe: At Days 29, 85, and 197 (28 days after each study intervention administration) compared to Day 1 (first study intervention administration baseline)
Stage 2: Number of participants with Anti-Vi Ag IgG antibody concentrations >= 4.3 µg/mL
Timeframe: 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)
Participation criteria
- Inclusion criteria
- Participants, who, in the opinion of the Investigator, can and will comply with the requirements of the protocol.
- 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.
Trial location(s)
Study documents
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Plain language summaries
To view plain language summaries on trialsummaries.com click here.