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Trial record 7 of 37 for:    "Shigellosis"

Safety, Immunogenicity and Efficacy of Shigella Conjugate Vaccines in 1-4 Year Olds in Israel

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ClinicalTrials.gov Identifier: NCT00368316
Recruitment Status : Completed
First Posted : August 24, 2006
Results First Posted : June 19, 2012
Last Update Posted : June 22, 2012
Sponsor:
Collaborators:
The Chaim Sheba Medical Center
Schneider Children's Medical Center, Israel
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )

Tracking Information
First Submitted Date  ICMJE August 22, 2006
First Posted Date  ICMJE August 24, 2006
Results First Submitted Date  ICMJE May 9, 2012
Results First Posted Date  ICMJE June 19, 2012
Last Update Posted Date June 22, 2012
Study Start Date  ICMJE January 2003
Actual Primary Completion Date January 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 21, 2012)
Number of Participants With Adverse Events [ Time Frame: Monitored for 7 days per participant following each injection for initial group of 500, 2 days for extended study of up to 5500 additional children ]
Number of participants with events per vaccine type and dose occuring in >=5% of participants
Original Primary Outcome Measures  ICMJE
 (submitted: August 22, 2006)
Evaluate the safety, immunogenicity and efficacy.
Change History Complete list of historical versions of study NCT00368316 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 21, 2012)
  • Geometric Mean Immunoglobulin G (IgG) Anti-Lipopolysaccharide (LPS) Levels [ Time Frame: Injections were administered 6 weeks apart and IgG anti-LPS levels determined >2 weeks after second vaccine dose. Each of the 15 sites also took a sample/week randomly chosen, for 2 years of follow up and blood samples from patients with disease ]
    Age-related homologous IgG anti-LPS levels
  • Percentage of Efficacy [ Time Frame: During 2 years post vaccination ]
    Percent efficacy is defined as ((disease rate of controls minus disease rate of vaccinees) divided by disease rate of controls) times 100
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety, Immunogenicity and Efficacy of Shigella Conjugate Vaccines in 1-4 Year Olds in Israel
Official Title  ICMJE Phase 3 Study (Safety, Immunogenicity and Efficacy) of Improved Shigella Conjugate Vaccines in 1-4 Year Olds in Israel
Brief Summary

Shigellosis remains a serious and frequent disease throughout the world. Development of vaccines has been difficult because shigellae are habitants of and pathogens for humans only and there is no consensus about the mechanism(s) of immunity to this pathogen.

Incomplete, but compelling evidence, indicates that a critical level of serum IgG anti-LPS confers immunity to shigellosis. Important data come from our clinical trial in the Israel Defense Forces (IDF) recruits. A randomized, double-blind, vaccine-controlled study showed that the S. sonnei-rEPA elicited 74% protection against shigellosis occurring about 3 months after vaccination (p=0.001). This vaccine conferred 43% (p=0.04) protection in one company during an outbreak up to 14 days following vaccination suggesting that our Shigella conjugates might be of value in epidemics. The efficacy of S. sonnei-rEPA was correlated with the level of vaccine-induced IgG antibodies.

The highest incidence, morbidity, and mortality of shigellosis is in young children. But serum antibody responsiveness to polysaccharide-based vaccines is age-dependent and infants and young children respond poorly or not at all to both disease and vaccination. The safety and immunogenicity of these Shigella conjugates in 4 to 6 years-old children in Israel was demonstrated. But although the fold rise in anti-LPS was similar in the children, the level of anti-LPS elicited by the conjugates was lower than in adults. We improved the immunogenicity of Shigella conjugates as shown in mice and then in adult humans. Now we apply to evaluate the safety, immunogenicity and efficacy of these improved conjugates in 1 to 4 years-old children in Israel.

In Israel, shigellosis is common especially in children. S. sonnei (Group D) comprise about 60% of the isolates followed by S. flexneri (Group B): Shigella dysenteriae type 1 (Group A) is not found. We propose to administer 2 injections of either S. sonnei-CRM9 or S. flexneri type 2a-rEPAsucc 6 weeks apart in a random double-blind fashion to about 6,000 1 to 4 year-olds. Active surveillance of the vaccinees for enteric infections will be maintained for at least 2 years to evaluate the effect of vaccination.

Detailed Description

Shigellosis remains a serious and frequent disease throughout the world. Development of vaccines has been difficult because shigellae are habitants of and pathogens for humans only and there is no consensus about the mechanism/s of immunity to this pathogen.

Incomplete, but compelling evidence, indicates that a critical level of serum IgG anti-LPS confers immunity to shigellosis. A randomized, double-blind, vaccine-controlled study in Israel Defense Force (IDF) recruits showed that the S. sonnei-rEPA elicited 74% protection against shigellosis occurring about 3 months after vaccination (p=0.001). This vaccine also conferred 43% (p=0.04) protection in one company during an outbreak up to 17 days following vaccination suggesting that our Shigella conjugates might be of value in epidemics. The efficacy of S. sonnei-rEPA was correlated with the level of vaccine-induced IgG antibodies.

The highest incidence, morbidity, and mortality of shigellosis is in young children. But serum antibody responsiveness to it is age dependent and infants and young children respond poorly or not at all to polysaccharide antigens following disease, administration of attenuated strains of Shigella or vaccination with whole cell vaccines. The safety and immunogenicity of similar Shigella conjugates in 4 to 7 years-old children in Israel was demonstrated. But, although the fold rise in anti-LPS was similar in the children, the level of anti-LPS elicited by the conjugates was lower than in adults. We improved the immunogenicity of Shigella conjugates as shown in mice and then in adult humans. Now we apply to evaluate the safety, immunogenicity and efficacy of these improved conjugates in 1 to 4 years-old children in Israel. In addition to monitoring the safety and immunogenicity of the two investigational Shigella vaccines, active surveillance of the vaccines for enteric infections wil be maintained for at lest 2 years to evaluate the effect of vaccination.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Shigellosis
Intervention  ICMJE Biological: Shigella conjugate vaccines
Shigella sonnei-rEPA and Shigella flexneri2a rEPA vaccines
Other Names:
  • S. sonnei O-SP-rEPA conjugate.
  • S. flexneri 2a O-SP-rEPA conjugate.
Study Arms  ICMJE
  • Experimental: S. sonnei conjugate vaccine
    Shigella sonnei O-specific polysaccharide covalently bound to recombinant exoprotein A of Pseudomonas aeruginosa
    Intervention: Biological: Shigella conjugate vaccines
  • Experimental: S. flexneri 2a conjugate vaccine
    Shigella flexneri 2a O-specific polysaccharide covalently bound to recombinant exoprotein A of pseudomonas aeruginosa
    Intervention: Biological: Shigella conjugate vaccines
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 9, 2012)
2799
Original Enrollment  ICMJE
 (submitted: August 22, 2006)
6080
Actual Study Completion Date  ICMJE February 2009
Actual Primary Completion Date January 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • INCLUSION CRITERIA:

Volunteers who are healthy 1-4 year old children whose parents/guardians have read the Information Sheet provided by the Principal Investigator and signed the consent form, and who will be available for follow up.

EXCLUSION CRITERIA: Children with

  • chronic diseases receiving medication;
  • who have received systemic steroids during the month preceding Shigella vaccination;
  • who had severe side effects following vaccinations; and
  • those not available for follow up.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 4 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel
Removed Location Countries United States
 
Administrative Information
NCT Number  ICMJE NCT00368316
Other Study ID Numbers  ICMJE 999900003
OH00-CH-N003 ( Registry Identifier: NICHD IRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
Study Sponsor  ICMJE Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators  ICMJE
  • The Chaim Sheba Medical Center
  • Schneider Children's Medical Center, Israel
Investigators  ICMJE
Principal Investigator: Rachel Schneerson, MD PDMI, NICHD, NIH
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date June 2012

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