Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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) )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Shigellosis
Intervention Biological: Shigella conjugate vaccines
Enrollment 2799
Recruitment Details Enrollment period: May 1, 2003 to January 31 3006. Surveillance period: May 1, 2003 to January 31 2008. Children were recruited from day care centers and health clinics in Israel
Pre-assignment Details  
Arm/Group Title S. Sonnei Conjugate Vaccine S. Flexneri 2a Conjugate Vaccine
Hide Arm/Group Description Shigella sonnei O-specific polysaccharide covalently bound to recombinant exoprotein A of Pseudomonas aeruginosa, administered in 2 injections of 0.5 mL containing 25 mcg of saccharide, 6 weeks apart Shigella flexneri 2a O-specific polysaccharide covalently bound to recombinant exoprotein A of Pseudomonas aeruginosa, administered in 2 injections of 0.5 mL containing 25 mcg of saccharide, 6 weeks apart
Period Title: Overall Study
Started 1434 1365
Completed 1392 1319
Not Completed 42 46
Arm/Group Title S. Sonnei Conjugate Vaccine S. Flexneri 2a Conjugate Vaccine Total
Hide Arm/Group Description Shigella sonnei O-specific polysaccharide covalently bound to recombinant exoprotein A of Pseudomonas aeruginosa, administered in 2 injections of 0.5 mL containing 25 mcg of saccharide, 6 weeks apart Shigella flexneri 2a O-specific polysaccharide covalently bound to recombinant exoprotein A of Pseudomonas aeruginosa, administered in 2 injections of 0.5 mL containing 25 mcg of saccharide, 6 weeks apart Total of all reporting groups
Overall Number of Baseline Participants 1434 1365 2799
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1434 participants 1365 participants 2799 participants
<=18 years
1434
 100.0%
1365
 100.0%
2799
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1434 participants 1365 participants 2799 participants
Female
702
  49.0%
642
  47.0%
1344
  48.0%
Male
732
  51.0%
723
  53.0%
1455
  52.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Israel Number Analyzed 1434 participants 1365 participants 2799 participants
1434 1365 2799
1.Primary Outcome
Title Number of Participants With Adverse Events
Hide Description Number of participants with events per vaccine type and dose occuring in >=5% of participants
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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title S. Sonnei Conjugate Vaccine S. Flexneri 2a Conjugate Vaccine
Hide Arm/Group Description:
Shigella sonnei O-specific polysaccharide covalently bound to recombinant exoprotein A of Pseudomonas aeruginosa, administered in 2 injections of 0.5 mL containing 25 mcg of saccharide, 6 weeks apart
Shigella flexneri 2a O-specific polysaccharide covalently bound to recombinant exoprotein A of Pseudomonas aeruginosa, administered in 2 injections of 0.5 mL containing 25 mcg of saccharide, 6 weeks apart
Overall Number of Participants Analyzed 1434 1365
Measure Type: Number
Unit of Measure: participants
local pain, dose 1 82 61
local pain, dose 2 79 64
fever, dose 1 56 72
fever, dose 2 36 51
2.Secondary Outcome
Title Geometric Mean Immunoglobulin G (IgG) Anti-Lipopolysaccharide (LPS) Levels
Hide Description Age-related homologous IgG anti-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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title S. Sonnei Conjugate Vaccine S. Flexneri 2a Conjugate Vaccine
Hide Arm/Group Description:
Shigella sonnei O-specific polysaccharide covalently bound to recombinant exoprotein A of Pseudomonas aeruginosa, administered in 2 injections of 0.5 mL containing 25 mcg of saccharide, 6 weeks apart
Shigella flexneri 2a O-specific polysaccharide covalently bound to recombinant exoprotein A of Pseudomonas aeruginosa, administered in 2 injections of 0.5 mL containing 25 mcg of saccharide, 6 weeks apart
Overall Number of Participants Analyzed 1434 1365
Geometric Mean (95% Confidence Interval)
Unit of Measure: ELISA units
Age 1-2 years
1.40 [1] 
(NA to NA)
18.98 [1] 
(NA to NA)
Age >2-3 years
3.71 [1] 
(NA to NA)
26.96 [1] 
(NA to NA)
Age >3-4 years
6.38 [1] 
(NA to NA)
43.86 [1] 
(NA to NA)
[1]
No measure of dispersion was calculated. The medically responsible investigator in Israel died.
3.Secondary Outcome
Title Percentage of Efficacy
Hide Description Percent efficacy is defined as ((disease rate of controls minus disease rate of vaccinees) divided by disease rate of controls) times 100
Time Frame During 2 years post vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title S. Sonnei Conjugate Vaccine S. Flexneri 2a Conjugate Vaccine
Hide Arm/Group Description:
Shigella sonnei O-specific polysaccharide covalently bound to recombinant exoprotein A of Pseudomonas aeruginosa, administered in 2 injections of 0.5 mL containing 25 mcg of saccharide, 6 weeks apart
Shigella flexneri 2a O-specific polysaccharide covalently bound to recombinant exoprotein A of Pseudomonas aeruginosa, administered in 2 injections of 0.5 mL containing 25 mcg of saccharide, 6 weeks apart
Overall Number of Participants Analyzed 1434 1365
Mean (95% Confidence Interval)
Unit of Measure: Percent efficacy
Participants aged 1-2 years
3.8
(-101.1 to 46.5)
-8.4
(-434.5 to 78.0)
Participants aged >2-3 years
35.5
(-56.4 to 73.4)
22.5
(-244.4 to 82.6)
Participants aged >3-4 years
71.1
(-4.43 to 92.0)
-3.6
(-1550 to 93.5)
Time Frame Local and systemic reactions were sought at 30 minutes, 6, 24 and 48 hours after vaccination by a structured questionnaire.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title S. Sonnei Conjugate Vaccine S. Flexneri 2a Conjugate Vaccine
Hide Arm/Group Description Shigella sonnei O-specific polysaccharide covalently bound to recombinant exoprotein A of Pseudomonas aeruginosa, administered in 2 injections of 0.5 mL containing 25 mcg of saccharide, 6 weeks apart Shigella flexneri 2a O-specific polysaccharide covalently bound to recombinant exoprotein A of Pseudomonas aeruginosa, administered in 2 injections of 0.5 mL containing 25 mcg of saccharide, 6 weeks apart
All-Cause Mortality
S. Sonnei Conjugate Vaccine S. Flexneri 2a Conjugate Vaccine
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
S. Sonnei Conjugate Vaccine S. Flexneri 2a Conjugate Vaccine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/1434 (0.00%)      0/1365 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
S. Sonnei Conjugate Vaccine S. Flexneri 2a Conjugate Vaccine
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   217/1434 (15.13%)      197/1365 (14.43%)    
General disorders     
fever, dose 2   36/1434 (2.51%)  36 72/1365 (5.27%)  72
Investigations     
fever, dose 1   56/1434 (3.91%)  56 72/1365 (5.27%)  72
Musculoskeletal and connective tissue disorders     
local pain, dose 1   82/1434 (5.72%)  82 61/1365 (4.47%)  61
local pain, dose 2   79/1434 (5.51%)  79 64/1365 (4.69%)  64
Indicates events were collected by systematic assessment
No efficacy could be assessed after 2nd injection of S. sonnei conjugate due to the small number of positive isolates at that time. There were too few cases of S. flexneri 2a infection for evaluation of vaccine B efficacy.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Rachel Schneerson, Co-Director
Organization: PDMI, NICHD, NIH
Phone: 301-469-0850
Responsible Party: National Institutes of Health Clinical Center (CC) ( Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) )
ClinicalTrials.gov Identifier: NCT00368316     History of Changes
Other Study ID Numbers: 999900003
OH00-CH-N003 ( Registry Identifier: NICHD IRB )
First Submitted: August 22, 2006
First Posted: August 24, 2006
Results First Submitted: May 9, 2012
Results First Posted: June 19, 2012
Last Update Posted: June 22, 2012