Immunogenicity, Safety and Tolerability of the Typhoid Fe... | NCT00679172

NCT00679172

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
M01ZH09 Vaccine Candidate Cohort 1	Experimental	Dose of 5.0 x 10^9 colony forming units (CFU) S. typhi (Ty2 aroC-ssaV-) ZH9 or placebo, administered as a single, oral dose	Biological: Dose of 5.0 x 10^9 CFU (Cohort 1) Other: Placebo (Cohorts 1-4 pooled)
M01ZH09 Vaccine Candidate Cohort 2	Experimental	Dose of 7.5 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9 or placebo, administered as a single, oral dose	Biological: Dose of 7.5 x 10^9 CFU (Cohort 2) Other: Placebo (Cohorts 1-4 pooled)
M01ZH09 Vaccine Candidate Cohort 3	Experimental	Dose of 1.1 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9 or placebo, administered as a single, oral dose	Biological: Dose of 1.1 x 10^10 CFU (Cohort 3) Other: Placebo (Cohorts 1-4 pooled)
M01ZH09 Vaccine Candidate Cohort 4	Experimental	Dose of of 1.7 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9 or placebo, administered as a single, oral dose	Biological: Dose of of 1.7 x 10^10 CFU (Cohort 4) Other: Placebo (Cohorts 1-4 pooled)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Dose of 5.0 x 10^9 CFU (Cohort 1)	Biological	S. typhi (Ty2 aroC-ssaV-) ZH9 live attenuated typhoid vaccine, single dose, oral administration	M01ZH09 Vaccine Candidate Cohort 1

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Number and Proportion of Subjects Reporting Suspected Unexpected Serious Adverse Reactions.	Number and proportion of subjects reporting suspected unexpected serious adverse reactions (SUSARs).	From start of dosing to 28 days post-dosing.
Number and Proportion of Subjects Experiencing Symptomatic Fever.	Number and proportion of subjects experiencing symptomatic (e.g., chills, rigors, sweating, headache, myalgia etc.) elevated body temperature of 38.0°C or more in the 14 days following dosing.	From start of dosing to 14 days post-dosing.
Number of Subjects Having Clinically Significant Changes in Laboratory Test Parameters.	Number of subjects having clinically significant changes in clinical laboratory test parameters.	From start of dosing to 28 days post-dosing.
Number of Subjects Reporting Treatment-related TEAEs.	Number of subjects having TEAEs considered by the principal investigator to be "possibly" or "probably" related to treatment.	From start of dosing to 28 days post-dosing.
Number and Proportion of Subjects Experiencing Bacteraemia.	Number and proportion of subjects experiencing a proven bacteraemia attributed to the vaccine strain S. typhi (Ty2 aroC-ssaV-) ZH9.	From start of dosing to 28 days post-dosing.
Number of Subjects Having Shedding in Stool of Salmonella Typhi (S. Typhi) (Ty2 aroC-ssaV-) ZH9.	Number of subjects having shedding in stool of S. typhi (Ty2 aroC-ssaV-) ZH9. Subjects were evaluated beyond Day 14 only in Cohort 4.

Secondary Outcomes

Measure	Description	Time Frame
Number and Proportion of Subjects Developing an Immune Response as Determined by the Level of IgA Antibodies for S. Typhi LPS.	Number and proportion of subjects with increase of 50% (fold change of 1.5) in S. typhi LPS-specific serum IgA at Days 7 or 14. Serum IgA was assayed using ELISA.	From baseline (pre-dose) to Days 7 or 14.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

healthy adult subjects aged 18 to 50 years inclusive, who are able and willing to give informed consent, following a detailed explanation of participation in protocol
available for the duration of the study and available for scheduled and potential additional visits

Exclusion Criteria:

women who are pregnant, breast-feeding or of childbearing potential and unwilling to use a reliable method of contraception throughout the study period
history of anaphylactic shock following vaccination by any route have phenylketonuria
hypersensitivity to any component of the vaccine or are hypersensitive to two of the following antibiotics: ciprofloxacin, azithromycin, ampicillin, trimethoprim sulfamethoxazole
received antibiotic medication within 14 days prior to dosing
received any vaccine within 4 weeks prior to dosing or plan to receive a vaccine within 4 weeks after dosing
received any vaccine against Salmonella typhi (licensed or investigational) or ever suffered from typhoid fever
subjects who test positive for hepatitis B, hepatitis C, HIV or human leucocyte antigen B-27
known or suspected history of liver or active gall bladder disease, ongoing gastro-intestinal disease or abnormality
commercial food handlers or health care workers with direct contact with high risk patients or who have household contacts with immuno-compromised individuals, pregnant women or children less than 2 years of age
subjects who have a clinically significant amount of protein or haemoglobin in their urine or abnormality of their haematology or serum biochemistry parameters
impairment of immune function or those receiving or have received cytotoxic drugs in the 6 months prior to study entry
subjects who use antacids, proton pump inhibitors or H2 blockers on a regular basis or have consumed proton pump inhibitors or H2 blockers within 24 hours prior to dosing
acute infections (including fever of 37.5 degrees Celsius or greater) on the day of dosing.
subjects with chronic disease (e.g Crohn's disease, inflammatory bowel disease, diabetes) who cannot withstand a 3 hour fast
substance abuse or a history of substance abuse that might interfere with participation in the study
body mass index (BMI) is less than 19 or greater than 34 kg per m2
clinically significant medical condition that precludes participation in the study
subjects who have participated in an interventional clinical trial within 60 days of dosing

Contacts/Locations Module

Name	Affiliation	Role
Stephen Lockhart, DM	Emergent BioSolutions	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Miami Research Associates		South Miami	Florida	33143	United States
John Hopkins Bloomberg School of Public Health

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
20188175	Result	Lyon CE, Sadigh KS, Carmolli MP, Harro C, Sheldon E, Lindow JC, Larsson CJ, Martinez T, Feller A, Ventrone CH, Sack DA, DeNearing B, Fingar A, Pierce K, Dill EA, Schwartz HI, Beardsworth EE, Kilonzo B, May JP, Lam W, Upton A, Budhram R, Kirkpatrick BD. In a randomized, double-blinded, placebo-controlled trial, the single oral dose typhoid vaccine, M01ZH09, is safe and immunogenic at doses up to 1.7 x 10(10) colony-forming units. Vaccine. 2010 Apr 30;28(20):3602-8. doi: 10.1016/j.vaccine.2010.02.017. Epub 2010 Feb 24.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	M01ZH09 Vaccine Candidate Cohort 1	Dose of 5.0 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
FG001	M01ZH09 Vaccine Candidate Cohort 2	Dose of 7.5 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

Type of Units Analyzed

Arm/Group Information

ID	Title	Description
BG000	M01ZH09 Vaccine Candidate Cohort 1	Dose of 5.0 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
BG001	M01ZH09 Vaccine Candidate Cohort 2	Dose of 7.5 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
BG002	M01ZH09 Vaccine Candidate Cohort 3	Dose of 1.1 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
BG003	M01ZH09 Vaccine Candidate Cohort 4	Dose of 1.7 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
BG004	Pooled Placebo	Placebo comparator comprised of excipients only, pooled across Cohorts 1-4.
BG005	Total	Total of all reporting groups

Units	Counts
Participants	BG00037 BG00138 BG00236 BG00339 BG00437 BG005187

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0001 BG0010 BG0021 BG003

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00033.2± 10.13 BG00133.1± 10.00 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00018 BG00117 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00037 BG00138 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Number and Proportion of Subjects Reporting Suspected Unexpected Serious Adverse Reactions.

Number and proportion of subjects reporting suspected unexpected serious adverse reactions (SUSARs).

Safety Population: All subjects who received a dose of study medication.

Posted

Count of Participants

Participants

From start of dosing to 28 days post-dosing.

ID	Title	Description
OG000	M01ZH09 Vaccine Candidate Cohort 1	Dose of 5.0 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG001	M01ZH09 Vaccine Candidate Cohort 2	Dose of 7.5 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG002	M01ZH09 Vaccine Candidate Cohort 3	Dose of 1.1 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG003	M01ZH09 Vaccine Candidate Cohort 4	Dose of 1.7 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG004	Pooled Placebo	Placebo comparator comprised of excipients only, pooled across Cohorts 1-4.

Units	Counts
Participants	OG00037 OG00138 OG00236 OG003

Title

Denominators

Categories

Title	Measurements
	OG0000 OG0010 OG0020 OG003

Primary

Number and Proportion of Subjects Experiencing Symptomatic Fever.

Number and proportion of subjects experiencing symptomatic (e.g., chills, rigors, sweating, headache, myalgia etc.) elevated body temperature of 38.0°C or more in the 14 days following dosing.

Safety Population: All subjects who received a dose of study medication.

Posted

Count of Participants

Participants

From start of dosing to 14 days post-dosing.

ID	Title	Description
OG000	M01ZH09 Vaccine Candidate Cohort 1	Dose of 5.0 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG001	M01ZH09 Vaccine Candidate Cohort 2	Dose of 7.5 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG002	M01ZH09 Vaccine Candidate Cohort 3	Dose of 1.1 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG003	M01ZH09 Vaccine Candidate Cohort 4	Dose of 1.7 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.

Primary

Number of Subjects Having Clinically Significant Changes in Laboratory Test Parameters.

Number of subjects having clinically significant changes in clinical laboratory test parameters.

Safety Population: All subjects who received a dose of study medication.

Posted

Number

participants

From start of dosing to 28 days post-dosing.

ID	Title	Description
OG000	M01ZH09 Vaccine Candidate Cohort 1	Dose of 5.0 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG001	M01ZH09 Vaccine Candidate Cohort 2	Dose of 7.5 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG002	M01ZH09 Vaccine Candidate Cohort 3	Dose of 1.1 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG003	M01ZH09 Vaccine Candidate Cohort 4	Dose of 1.7 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG004	Pooled Placebo

Primary

Number of Subjects Reporting Treatment-related TEAEs.

Number of subjects having TEAEs considered by the principal investigator to be "possibly" or "probably" related to treatment.

Safety Population: All subjects who received a dose of study medication.

Posted

Number

participants

From start of dosing to 28 days post-dosing.

ID	Title	Description
OG000	M01ZH09 Vaccine Candidate Cohort 1	Dose of 5.0 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG001	M01ZH09 Vaccine Candidate Cohort 2	Dose of 7.5 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG002	M01ZH09 Vaccine Candidate Cohort 3	Dose of 1.1 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG003	M01ZH09 Vaccine Candidate Cohort 4	Dose of 1.7 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG004	Pooled Placebo

Primary

Number and Proportion of Subjects Experiencing Bacteraemia.

Number and proportion of subjects experiencing a proven bacteraemia attributed to the vaccine strain S. typhi (Ty2 aroC-ssaV-) ZH9.

Safety Population: All subjects who received a dose of study medication.

Posted

Count of Participants

Participants

From start of dosing to 28 days post-dosing.

ID	Title	Description
OG000	M01ZH09 Vaccine Candidate Cohort 1	Dose of 5.0 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG001	M01ZH09 Vaccine Candidate Cohort 2	Dose of 7.5 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG002	M01ZH09 Vaccine Candidate Cohort 3	Dose of 1.1 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG003	M01ZH09 Vaccine Candidate Cohort 4	Dose of 1.7 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG004	Pooled Placebo

Primary

Number of Subjects Having Shedding in Stool of Salmonella Typhi (S. Typhi) (Ty2 aroC-ssaV-) ZH9.

Number of subjects having shedding in stool of S. typhi (Ty2 aroC-ssaV-) ZH9. Subjects were evaluated beyond Day 14 only in Cohort 4.

Safety Population: All subjects who received a dose of study medication.

Posted

Number

participants

Beyond 7 days post-dosing through 14 days post-dosing (Cohorts 1-3) or through 21 days post-dosing (Cohort 4).

ID	Title	Description
OG000	M01ZH09 Vaccine Candidate Cohort 1	Dose of 5.0 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG001	M01ZH09 Vaccine Candidate Cohort 2	Dose of 7.5 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG002	M01ZH09 Vaccine Candidate Cohort 3	Dose of 1.1 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG003	M01ZH09 Vaccine Candidate Cohort 4	Dose of 1.7 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.

Primary

Number and Proportion of Subjects Developing an Immune Response as Determined by the Level of IgG and/or IgA Antibodies for S. Typhi Lipopolysaccharide (LPS).

Number and proportion of subjects with increase of 70% (fold change of 1.7) in S. typhi LPS-specific serum IgG at Days 14 or 28 AND/OR increase of 50% (fold change of 1.5) in S. typhi LPS-specific serum IgA at Days 7 or 14. Serum IgG and IgA were assayed using enzyme-linked immunosorbent assay (ELISA).

ITT Population: all subjects who received study medication and had any postbaseline immunogenicity data available up to and including Day 28.

Posted

Count of Participants

Participants

From baseline (pre-dose) to Days 14 or 28 (IgG) or to Days 7 or 14 (IgA).

ID	Title	Description
OG000	M01ZH09 Vaccine Candidate Cohort 1	Dose of 5.0 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG001	M01ZH09 Vaccine Candidate Cohort 2	Dose of 7.5 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG002	M01ZH09 Vaccine Candidate Cohort 3	Dose of 1.1 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG003

Secondary

Number and Proportion of Subjects Developing an Immune Response as Determined by the Level of IgA Antibodies for S. Typhi LPS.

Number and proportion of subjects with increase of 50% (fold change of 1.5) in S. typhi LPS-specific serum IgA at Days 7 or 14. Serum IgA was assayed using ELISA.

ITT Population: all subjects who received study medication and had any postbaseline immunogenicity data available up to and including Day 28.

Posted

Count of Participants

Participants

From baseline (pre-dose) to Days 7 or 14.

ID	Title	Description
OG000	M01ZH09 Vaccine Candidate Cohort 1	Dose of 5.0 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG001	M01ZH09 Vaccine Candidate Cohort 2	Dose of 7.5 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG002	M01ZH09 Vaccine Candidate Cohort 3	Dose of 1.1 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG003	M01ZH09 Vaccine Candidate Cohort 4	Dose of 1.7 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.

Secondary

Number and Proportion of Subjects Developing an Immune Response as Determined by the Level of IgG Antibodies for S. Typhi LPS.

Number and proportion of subjects with increase of 70% (fold change of 1.7) in S. typhi LPS-specific serum IgG at Days 14 or 28. Serum IgG was assayed using ELISA.

ITT Population: all subjects who received study medication and had any postbaseline immunogenicity data available up to and including Day 28.

Posted

Count of Participants

Participants

From baseline (pre-dose) to Days 14 or 28.

ID	Title	Description
OG000	M01ZH09 Vaccine Candidate Cohort 1	Dose of 5.0 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG001	M01ZH09 Vaccine Candidate Cohort 2	Dose of 7.5 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG002	M01ZH09 Vaccine Candidate Cohort 3	Dose of 1.1 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG003	M01ZH09 Vaccine Candidate Cohort 4	Dose of 1.7 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.

Secondary

Number and Proportion of Subjects Developing an Immune Response as Determined by the Level of IgG Antibodies for S. Typhi LPS.

Number and proportion of subjects with an increase of 70% (fold change of 1.7) in S. typhi LPS-specific serum IgG at Days 7, 14 or 28. Serum IgG was assayed using ELISA.

ITT Population: all subjects who received study medication and had any postbaseline immunogenicity data available up to and including Day 14.

Posted

Count of Participants

Participants

From baseline (pre-dose) to Days 7, 14, or 28.

ID	Title	Description
OG000	M01ZH09 Vaccine Candidate Cohort 1	Dose of 5.0 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG001	M01ZH09 Vaccine Candidate Cohort 2	Dose of 7.5 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG002	M01ZH09 Vaccine Candidate Cohort 3	Dose of 1.1 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG003	M01ZH09 Vaccine Candidate Cohort 4	Dose of 1.7 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.

Secondary

Number and Proportion of Subjects Developing an Immune Response at the Target Dose of 7.5 x 10^9 CFU (Cohort 2) as Determined by the Number of Antibody Secreting Cells (ASCs) Secreting IgA and/or Fold Change in IgG.

Number and proportion of subjects with ≥ 4 ASCs per 10^6 peripheral blood mononuclear cells (PBMCs) at Day 7 secreting IgA specific for S. typhi LPS (detected by enzyme-linked immunospot assay [ELISPOT]) AND/OR 4-fold increase for serum IgG on Day 28 compared to baseline (assay using endpoint titre ELISA).

ITT Population (Cohort 2): all subjects who received study medication and had any postbaseline immunogenicity data available up to and including Day 28.

Posted

Count of Participants

Participants

At Day 7 (IgA); and from baseline (pre-dose) to Day 28 (IgG).

ID	Title	Description
OG000	M01ZH09 Vaccine Candidate Cohort 2	Dose of 7.5 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG001	Placebo - Cohort 2	Placebo comparator comprised of excipients only - Cohort 2

Units	Counts
Participants

Secondary

Number and Proportion of Subjects Developing an Immune Response at the Target Dose of 7.5 x 10^9 CFU (Cohort 2) as Determined by the Number of ASCs Secreting IgA.

Number and proportion of subjects with ≥ 4 ASCs per 10^6 PBMCs at Day 7 secreting IgA specific for S. typhi LPS (detected by ELISPOT).

ITT Population (Cohort 2): all subjects who received study medication and had any postbaseline immunogenicity data available up to and including Day 28.

Posted

Count of Participants

Participants

Day 7.

ID	Title	Description
OG000	M01ZH09 Vaccine Candidate Cohort 2	Dose of 7.5 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG001	Placebo - Cohort 2	Placebo comparator comprised of excipients only - Cohort 2

Units	Counts
Participants	OG000

Secondary

Number and Proportion of Subjects Developing an Immune Response at the Target Dose of 7.5 x 10^9 CFU (Cohort 2) as Determined by the Fold Change in IgG.

Number and proportion of subjects with 4-fold increase for serum IgG on Day 28 compared to baseline (assay using endpoint titre ELISA).

ITT Population (Cohort 2): all subjects who received study medication and had any postbaseline immunogenicity data available up to and including Day 28.

Posted

Count of Participants

Participants

From baseline (pre-dose) to Day 28.

ID	Title	Description
OG000	M01ZH09 Vaccine Candidate Cohort 2	Dose of 7.5 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.
OG001	Placebo - Cohort 2	Placebo comparator comprised of excipients only - Cohort 2

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	M01ZH09 Vaccine Candidate Cohort 1	Dose of 5.0 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.	37	37	27	37
EG001	M01ZH09 Vaccine Candidate Cohort 2	Dose of 7.5 x 10^9 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.	38	38	26	38
EG002	M01ZH09 Vaccine Candidate Cohort 3	Dose of 1.1 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.	36	36	30	36
EG003	M01ZH09 Vaccine Candidate Cohort 4	Dose of 1.7 x 10^10 CFU S. typhi (Ty2 aroC-ssaV-) ZH9.	39	39	33	39
EG004	Pooled Placebo	Placebo comparator comprised of excipients only, pooled across Cohorts 1-4.	37	37	31	37

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA (11.0)	Non-systematic Assessment	EG00011 affected37 at risk EG00112 affected38 at risk EG0027 affected36 at risk EG00312 affected39 at risk EG0048 affected37 at risk
Constipation	Gastrointestinal disorders	MedDRA (11.0)	Non-systematic Assessment	EG0007 affected37 at risk EG0014 affected38 at risk EG0021 affected36 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA (11.0)	Non-systematic Assessment	EG0005 affected37 at risk EG00110 affected38 at risk EG0026 affected36 at risk EG003
Flatulence	Gastrointestinal disorders	MedDRA (11.0)	Non-systematic Assessment	EG00017 affected37 at risk EG00115 affected38 at risk EG00210 affected36 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA (11.0)	Non-systematic Assessment	EG0009 affected37 at risk EG0016 affected38 at risk EG0023 affected36 at risk EG003
Asthenia	General disorders	MedDRA (11.0)	Non-systematic Assessment	EG0008 affected37 at risk EG00113 affected38 at risk EG0026 affected36 at risk EG003
Anorexia	Metabolism and nutrition disorders	MedDRA (11.0)	Non-systematic Assessment	EG0003 affected37 at risk EG0018 affected38 at risk EG0021 affected36 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA (11.0)	Non-systematic Assessment	EG0004 affected37 at risk EG0016 affected38 at risk EG0023 affected36 at risk EG003
Headache	Nervous system disorders	MedDRA (11.0)	Non-systematic Assessment	EG00016 affected37 at risk EG0015 affected38 at risk EG0029 affected36 at risk EG003
Dyspepsia	Gastrointestinal disorders	MedDRA (11.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0011 affected38 at risk EG0022 affected36 at risk EG003
Chills	General disorders	MedDRA (11.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0010 affected38 at risk EG0022 affected36 at risk EG003
Fatigue	General disorders	MedDRA (11.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0010 affected38 at risk EG0020 affected36 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA (11.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0011 affected38 at risk EG0022 affected36 at risk EG003
Culture stool positive	Investigations	MedDRA (11.0)	Non-systematic Assessment	EG0001 affected37 at risk EG0011 affected38 at risk EG0021 affected36 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA (11.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0011 affected38 at risk EG0021 affected36 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA (11.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0010 affected38 at risk EG0020 affected36 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	MedDRA (11.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0010 affected38 at risk EG0023 affected36 at risk EG003
Dizziness	Nervous system disorders	MedDRA (11.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0011 affected38 at risk EG0022 affected36 at risk EG003
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA (11.0)	Non-systematic Assessment	EG0000 affected18 at risk EG0011 affected17 at risk EG0022 affected19 at risk EG003
Pharyngolaryngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA (11.0)	Non-systematic Assessment	EG0002 affected37 at risk EG0011 affected38 at risk EG0020 affected36 at risk EG003
Anaemia	Blood and lymphatic system disorders	MedDRA (11.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0010 affected38 at risk EG0020 affected36 at risk EG003
Muscle spasms	Musculoskeletal and connective tissue disorders	MedDRA (11.0)	Non-systematic Assessment	EG0000 affected37 at risk EG0010 affected38 at risk EG0020 affected36 at risk EG003

ID	Term
D014435	Typhoid Fever

Ancestor Terms

ID	Term
D012480	Salmonella Infections
D004756	Enterobacteriaceae Infections
D016905	Gram-Negative Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses
D007239	Infections

EG0048 affected37 at risk

EG00410 affected37 at risk

EG00414 affected37 at risk

EG0045 affected37 at risk

EG0048 affected37 at risk

EG0047 affected37 at risk

EG00413 affected37 at risk

EG0040 affected37 at risk

EG0041 affected37 at risk

EG0043 affected37 at risk

EG0040 affected37 at risk

EG0041 affected37 at risk

EG0042 affected37 at risk

EG0041 affected37 at risk

EG0041 affected21 at risk

EG0042 affected37 at risk