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Immunogenicity, Safety and Tolerability of the Typhoid Fever Vaccine Candidate M01ZH09 in Healthy Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Emergent BioSolutions
ClinicalTrials.gov Identifier:
NCT00679172
First received: May 14, 2008
Last updated: June 6, 2017
Last verified: June 2017
May 14, 2008
June 6, 2017
May 2008
December 2008   (Final data collection date for primary outcome measure)
  • 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 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.
  • 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).
  • Safety (including the proportion of subjects reporting adverse events (AEs) and serious adverse events (SAEs)). [ Time Frame: From day of dosing to 28 days post-dosing under double-blind conditions with 3 month open follow-up ]
  • Immunogenicity (level of IgG and IgA antibodies for Salmonella typhi lipopolysaccharide post-dosing, in comparison to baseline levels). [ Time Frame: Days 7, 14 and 28 post-dosing ]
Complete list of historical versions of study NCT00679172 on ClinicalTrials.gov Archive Site
  • Number and Proportion of Subjects Developing an Immune Response as Determined by the Level of IgA Antibodies for S. Typhi LPS. [ Time Frame: From baseline (pre-dose) to Days 7 or 14. ]
    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.
  • Number and Proportion of Subjects Developing an Immune Response as Determined by the Level of IgG Antibodies for S. Typhi LPS. [ Time Frame: From baseline (pre-dose) to Days 14 or 28. ]
    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.
  • Number and Proportion of Subjects Developing an Immune Response as Determined by the Level of IgG Antibodies for S. Typhi LPS. [ Time Frame: From baseline (pre-dose) to Days 7, 14, or 28. ]
    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.
  • 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. [ Time Frame: At Day 7 (IgA); and from baseline (pre-dose) to Day 28 (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).
  • 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. [ Time Frame: Day 7. ]
    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).
  • 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. [ Time Frame: From baseline (pre-dose) to Day 28. ]
    Number and proportion of subjects with 4-fold increase for serum IgG on Day 28 compared to baseline (assay using endpoint titre ELISA).
Immunogenicity (Number of cells secreting IgA antibodies for Salmonella typhi lipopolysaccharide) [ Time Frame: Day 7 post-dosing ]
Not Provided
Not Provided
 
Immunogenicity, Safety and Tolerability of the Typhoid Fever Vaccine Candidate M01ZH09 in Healthy Adults
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.
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.
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).
Interventional
Phase 2
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Typhoid
  • Biological: Dose of 5.0 x 10^9 CFU (Cohort 1)
    S. typhi (Ty2 aroC‾ssaV‾) ZH9 live attenuated typhoid vaccine, single dose, oral administration
  • Biological: Dose of 7.5 x 10^9 CFU (Cohort 2)
    S. typhi (Ty2 aroC‾ssaV‾) ZH9 live attenuated typhoid vaccine, single dose, oral administration
  • Biological: Dose of 1.1 x 10^10 CFU (Cohort 3)
    S. typhi (Ty2 aroC‾ssaV‾) ZH9 live attenuated typhoid vaccine, single dose, oral administration
  • Biological: Dose of of 1.7 x 10^10 CFU (Cohort 4)
    S. typhi (Ty2 aroC‾ssaV‾) ZH9 live attenuated typhoid vaccine, single dose, oral administration
  • Other: Placebo (Cohorts 1-4 pooled)
    Excipients only, single dose, oral administration
  • Experimental: M01ZH09 Vaccine Candidate Cohort 1
    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
    Interventions:
    • Biological: Dose of 5.0 x 10^9 CFU (Cohort 1)
    • Other: Placebo (Cohorts 1-4 pooled)
  • Experimental: M01ZH09 Vaccine Candidate Cohort 2
    Dose of 7.5 x 10^9 CFU S. typhi (Ty2 aroC‾ssaV‾) ZH9 or placebo, administered as a single, oral dose
    Interventions:
    • Biological: Dose of 7.5 x 10^9 CFU (Cohort 2)
    • Other: Placebo (Cohorts 1-4 pooled)
  • Experimental: M01ZH09 Vaccine Candidate Cohort 3
    Dose of 1.1 x 10^10 CFU S. typhi (Ty2 aroC‾ssaV‾) ZH9 or placebo, administered as a single, oral dose
    Interventions:
    • Biological: Dose of 1.1 x 10^10 CFU (Cohort 3)
    • Other: Placebo (Cohorts 1-4 pooled)
  • Experimental: M01ZH09 Vaccine Candidate Cohort 4
    Dose of of 1.7 x 10^10 CFU S. typhi (Ty2 aroC‾ssaV‾) ZH9 or placebo, administered as a single, oral dose
    Interventions:
    • Biological: Dose of of 1.7 x 10^10 CFU (Cohort 4)
    • Other: Placebo (Cohorts 1-4 pooled)
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
187
December 2008
December 2008   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
18 Years to 50 Years   (Adult)
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT00679172
MS01.13
No
Not Provided
Plan to Share IPD: No
Emergent BioSolutions
Emergent BioSolutions
Not Provided
Study Director: Stephen Lockhart, DM Emergent BioSolutions
Emergent BioSolutions
June 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP