A Randomised, Double-blind, Placebo-controlled, Single Dose, Dose Escalation Study to Determine the Immunogenicity, Safety and Tolerability of S. Typhi (Ty2 aroC-ssaV-) ZH9 at Doses of 5.0 x 10E9 CFU, 7.5 x 10E9 CFU, 1.1 x 10E10 and 1.7 x 10E10 CFU and 1.7 x 10E10 CFU, Following Oral Administration to Healthy, Typhoid Vaccine naïve Subjects in the USA.
Overview
- Phase
- Phase 2
- Intervention
- Not specified
- Conditions
- Typhoid
- Sponsor
- Emergent BioSolutions
- Enrollment
- 187
- Locations
- 3
- Primary Endpoint
- Number and Proportion of Subjects Reporting Suspected Unexpected Serious Adverse Reactions.
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This study is to investigate the safety, tolerability and immunogenicity of the typhoid fever vaccine candidate M01ZH09 manufactured at commercial scale, at a new manufacturing facility. The vaccine will be delivered as a single oral dose to healthy, typhoid vaccine-naïve adults.
Detailed Description
This was a randomised, double-blind, placebo-controlled, single dose, dose escalation study with 4 dosing cohorts. Within each cohort, 45 evaluable subjects were planned (36 subjects receiving M01ZH09, 9 receiving placebo).
Investigators
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
Outcomes
Primary Outcomes
Number and Proportion of Subjects Reporting Suspected Unexpected Serious Adverse Reactions.
Time Frame: From start of dosing to 28 days post-dosing.
Number and proportion of subjects reporting suspected unexpected serious adverse reactions (SUSARs).
Number and Proportion of Subjects Experiencing Symptomatic Fever.
Time Frame: From start of dosing to 14 days post-dosing.
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.
Number and Proportion of Subjects Experiencing Bacteraemia.
Time Frame: From start of dosing to 28 days post-dosing.
Number and proportion of subjects experiencing a proven bacteraemia attributed to the vaccine strain S. typhi (Ty2 aroC-ssaV-) ZH9.
Number of Subjects Having Shedding in Stool of Salmonella Typhi (S. Typhi) (Ty2 aroC-ssaV-) ZH9.
Time Frame: Beyond 7 days post-dosing through 14 days post-dosing (Cohorts 1-3) or through 21 days post-dosing (Cohort 4).
Number of subjects having shedding in stool of S. typhi (Ty2 aroC-ssaV-) ZH9. Subjects were evaluated beyond Day 14 only in Cohort 4.
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).
Time Frame: From baseline (pre-dose) to Days 14 or 28 (IgG) or to Days 7 or 14 (IgA).
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).
Number of Subjects Having Clinically Significant Changes in Laboratory Test Parameters.
Time Frame: From start of dosing to 28 days post-dosing.
Number of subjects having clinically significant changes in clinical laboratory test parameters.
Number of Subjects Reporting Treatment-related TEAEs.
Time Frame: From start of dosing to 28 days post-dosing.
Number of subjects having TEAEs considered by the principal investigator to be "possibly" or "probably" related to treatment.
Secondary Outcomes
- Number and Proportion of Subjects Developing an Immune Response as Determined by the Level of IgA Antibodies for S. Typhi LPS.(From baseline (pre-dose) to Days 7 or 14.)
- 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.(At Day 7 (IgA); and from baseline (pre-dose) to Day 28 (IgG).)
- 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.(Day 7.)
- Number and Proportion of Subjects Developing an Immune Response as Determined by the Level of IgG Antibodies for S. Typhi LPS.(From baseline (pre-dose) to Days 7, 14, or 28.)
- 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.(From baseline (pre-dose) to Day 28.)