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Safety and Immunogenicity of Vi-CRM197 Vaccine Against S. Typhi in Children, Older Infants and Infants

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ClinicalTrials.gov Identifier: NCT01437267
Recruitment Status : Completed
First Posted : September 20, 2011
Results First Posted : April 10, 2014
Last Update Posted : April 10, 2014
Sponsor:
Information provided by (Responsible Party):
Novartis

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Typhoid Fever
Interventions Biological: Vi-CRM197 vaccine
Biological: Pneumococcal conjugate vaccine
Biological: Vi Polysaccharide (PS) vaccine
Enrollment 120
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Vi-CRM, Children Vi-PS, Children Vi-CRM, Older Infants PNC13, Older Infants Vi-CRM, Infants PNC13, Infants
Hide Arm/Group Description Children (24 to 59 months) receiving 2 doses of NVGH Vi-CRM197 vaccine Children (24 to 59 months) receiving 1 dose of licensed Vi Polysaccharide vaccine and 1 dose of Pneumococcal conjugate vaccine Older Infants (9 to 12 months) receiving 2 doses of NVGH Vi-CRM197 vaccine Older infants (9 to 12 months) receiving 2 doses of Pneumococcal conjugate vaccine Infants (6 to 8 weeks) receiving 3 doses of NVGH Vi-CRM197 vaccine Infants (6 to 8 weeks) receiving 3 doses of Pneumococcal conjugate vaccine
Period Title: Overall Study
Started 20 20 20 20 20 20
Completed 20 19 20 19 20 20
Not Completed 0 1 0 1 0 0
Reason Not Completed
Withdrawal by Subject             0             0             0             1             0             0
Protocol Violation             0             1             0             0             0             0
Arm/Group Title Vi-CRM, Children Vi-PS, Children Vi-CRM, Older Infants PNC13, Older Infants Vi-CRM, Infants PNC13, Infants Total
Hide Arm/Group Description Children (24 to 59 months) receiving 2 doses of NVGH Vi-CRM197 vaccine Children (24 to 59 months) receiving 1 dose of licensed Vi Polysaccharide vaccine and 1 dose of Pneumococcal conjugate vaccine Older Infants (9 to 12 months) receiving 2 doses of NVGH Vi-CRM197 vaccine Older infants (9 to 12 months) receiving 2 doses of Pneumococcal conjugate vaccine Infants (6 to 8 weeks) receiving 3 doses of NVGH Vi-CRM197 vaccine Infants (6 to 8 weeks) receiving 3 doses of Pneumococcal conjugate vaccine Total of all reporting groups
Overall Number of Baseline Participants 20 20 20 20 20 20 120
Hide Baseline Analysis Population Description
Analysis was done on all enrolled subjects.
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 20 participants 20 participants 20 participants 20 participants 20 participants 20 participants 120 participants
6 weeks to 8 weeks (infants) 0 0 0 0 20 20 40
9 months to 12 months (older infants) 0 0 20 20 0 0 40
24 months 59 months (children) 20 20 0 0 0 0 40
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 20 participants 20 participants 20 participants 20 participants 20 participants 120 participants
Female
12
  60.0%
10
  50.0%
12
  60.0%
14
  70.0%
11
  55.0%
10
  50.0%
69
  57.5%
Male
8
  40.0%
10
  50.0%
8
  40.0%
6
  30.0%
9
  45.0%
10
  50.0%
51
  42.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 20 participants 20 participants 20 participants 20 participants 20 participants 120 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
20
 100.0%
20
 100.0%
20
 100.0%
20
 100.0%
20
 100.0%
20
 100.0%
120
 100.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Philippines Number Analyzed 20 participants 20 participants 20 participants 20 participants 20 participants 20 participants 120 participants
20 20 20 20 20 20 120
1.Primary Outcome
Title Percentage of Subjects With at Least 4-fold Increase in Anti-Vi Enzyme-linked Immunosorbent Assay (ELISA) Titer
Hide Description [Not Specified]
Time Frame At 28 days after last vaccination as compared to baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat analysis set, which included all participants who received the vaccination, those in whom at least one post-vaccination blood sample was collected, and those for whom at least one ELISA result was available.
Arm/Group Title Vi-CRM, Children Vi-PS, Children Vi-CRM, Older Infants PNC13, Older Infants Vi-CRM, Infants PNC13, Infants
Hide Arm/Group Description:
Children (24 to 59 months) receiving 2 doses of NVGH Vi-CRM197 vaccine
Children (24 to 59 months) receiving 1 dose of licensed Vi Polysaccharide vaccine and 1 dose of Pneumococcal conjugate vaccine
Older Infants (9 to 12 months) receiving 2 doses of NVGH Vi-CRM197 vaccine
Older infants (9 to 12 months) receiving 2 doses of Pneumococcal conjugate vaccine
Infants (6 to 8 weeks) receiving 3 doses of NVGH Vi-CRM197 vaccine
Infants (6 to 8 weeks) receiving 3 doses of Pneumococcal conjugate vaccine
Overall Number of Participants Analyzed 20 19 20 19 20 20
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of subjects
100
(83 to 100)
100
(82 to 100)
100
(83 to 100)
11
(1 to 33)
100
(83 to 100)
10
(1 to 32)
2.Primary Outcome
Title Percentage of Subjects With at Least 4-fold Increase in Anti-Vi ELISA Titer
Hide Description [Not Specified]
Time Frame At 6 months after last vaccination as compared to baseline
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat analysis set
Arm/Group Title Vi-CRM, Children Vi-PS, Children Vi-CRM, Older Infants PNC13, Older Infants Vi-CRM, Infants PNC13, Infants
Hide Arm/Group Description:
Children (24 to 59 months) receiving 2 doses of NVGH Vi-CRM197 vaccine
Children (24 to 59 months) receiving 1 dose of licensed Vi Polysaccharide vaccine and 1 dose of Pneumococcal conjugate vaccine
Older Infants (9 to 12 months) receiving 2 doses of NVGH Vi-CRM197 vaccine
Older infants (9 to 12 months) receiving 2 doses of Pneumococcal conjugate vaccine
Infants (6 to 8 weeks) receiving 3 doses of NVGH Vi-CRM197 vaccine
Infants (6 to 8 weeks) receiving 3 doses of Pneumococcal conjugate vaccine
Overall Number of Participants Analyzed 20 19 20 19 20 20
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of subjects
90
(68 to 99)
95
(74 to 100)
70
(46 to 88)
11
(1 to 33)
70
(46 to 88)
5
(0 to 25)
3.Primary Outcome
Title Anti-Vi ELISA Geometric Mean Concentration (GMC)
Hide Description [Not Specified]
Time Frame At 28 days after last vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat analysis set
Arm/Group Title Vi-CRM, Children Vi-PS, Children Vi-CRM, Older Infants PNC13, Older Infants Vi-CRM, Infants PNC13, Infants
Hide Arm/Group Description:
Children (24 to 59 months) receiving 2 doses of NVGH Vi-CRM197 vaccine
Children (24 to 59 months) receiving 1 dose of licensed Vi Polysaccharide vaccine and 1 dose of Pneumococcal conjugate vaccine
Older Infants (9 to 12 months) receiving 2 doses of NVGH Vi-CRM197 vaccine
Older infants (9 to 12 months) receiving 2 doses of Pneumococcal conjugate vaccine
Infants (6 to 8 weeks) receiving 3 doses of NVGH Vi-CRM197 vaccine
Infants (6 to 8 weeks) receiving 3 doses of Pneumococcal conjugate vaccine
Overall Number of Participants Analyzed 20 19 20 19 20 20
Geometric Mean (95% Confidence Interval)
Unit of Measure: ELISA Units/mL
255
(174 to 375)
107
(72 to 159)
129
(83 to 200)
3.79
(2.41 to 5.97)
103
(67 to 159)
5.05
(3.27 to 7.79)
4.Primary Outcome
Title Anti-Vi ELISA GMC
Hide Description [Not Specified]
Time Frame At 6 months after last vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Intention-to-treat analysis set
Arm/Group Title Vi-CRM, Children Vi-PS, Children Vi-CRM, Older Infants PNC13, Older Infants Vi-CRM, Infants PNC13, Infants
Hide Arm/Group Description:
Children (24 to 59 months) receiving 2 doses of NVGH Vi-CRM197 vaccine
Children (24 to 59 months) receiving 1 dose of licensed Vi Polysaccharide vaccine and 1 dose of Pneumococcal conjugate vaccine
Older Infants (9 to 12 months) receiving 2 doses of NVGH Vi-CRM197 vaccine
Older infants (9 to 12 months) receiving 2 doses of Pneumococcal conjugate vaccine
Infants (6 to 8 weeks) receiving 3 doses of NVGH Vi-CRM197 vaccine
Infants (6 to 8 weeks) receiving 3 doses of Pneumococcal conjugate vaccine
Overall Number of Participants Analyzed 20 19 20 19 20 20
Geometric Mean (95% Confidence Interval)
Unit of Measure: ELISA Units/mL
51
(34 to 76)
45
(30 to 68)
21
(14 to 31)
3.69
(2.41 to 5.65)
21
(16 to 28)
2.64
(1.98 to 3.52)
5.Secondary Outcome
Title Number of Participants With Any Solicited Local and Systemic Reaction, After Any Vaccination
Hide Description Solicited local reactions were: erythema, induration, pain/tenderness. Solicited systemic reactions were; lethargy, irritability, vomiting, diarrhoea, loss of appetite (and persistent crying in the older infants and infants age group)
Time Frame During the 7-day follow-up period after vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis was done on as treated safety population
Arm/Group Title Vi-CRM, Children Vi-PS, Children Vi-CRM, Older Infants PNC13, Older Infants Vi-CRM, Infants PNC13, Infants
Hide Arm/Group Description:
Children (24 to 59 months) receiving 2 doses of NVGH Vi-CRM197 vaccine
Children (24 to 59 months) receiving 1 dose of licensed Vi Polysaccharide vaccine and 1 dose of Pneumococcal conjugate vaccine
Older Infants (9 to 12 months) receiving 2 doses of NVGH Vi-CRM197 vaccine
Older infants (9 to 12 months) receiving 2 doses of Pneumococcal conjugate vaccine
Infants (6 to 8 weeks) receiving 3 doses of NVGH Vi-CRM197 vaccine
Infants (6 to 8 weeks) receiving 3 doses of Pneumococcal conjugate vaccine
Overall Number of Participants Analyzed 20 20 20 20 20 20
Measure Type: Number
Unit of Measure: participants
11 10 12 17 20 19
Time Frame Solicited Adverse Events (AEs) were collected during 7-day follow period after each vaccination. Serious AEs were collected throughout the study period. Unsolicited AEs were collected collected during 28-day follow period after each vaccination.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Vi-CRM, Children Vi-PS, Children Vi-CRM, Older Infants PNC13, Older Infants Vi-CRM, Infants PNC13, Infants
Hide Arm/Group Description Children (24 to 59 months) receiving 2 doses of NVGH Vi-CRM197 vaccine Children (24 to 59 months) receiving 1 dose of licensed Vi Polysaccharide vaccine and 1 dose of Pneumococcal conjugate vaccine Older Infants (9 to 12 months) receiving 2 doses of NVGH Vi-CRM197 vaccine Older infants (9 to 12 months) receiving 2 doses of Pneumococcal conjugate vaccine Infants (6 to 8 weeks) receiving 3 doses of NVGH Vi-CRM197 vaccine Infants (6 to 8 weeks) receiving 3 doses of Pneumococcal conjugate vaccine
All-Cause Mortality
Vi-CRM, Children Vi-PS, Children Vi-CRM, Older Infants PNC13, Older Infants Vi-CRM, Infants PNC13, Infants
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Vi-CRM, Children Vi-PS, Children Vi-CRM, Older Infants PNC13, Older Infants Vi-CRM, Infants PNC13, Infants
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/20 (0.00%)   1/20 (5.00%)   0/20 (0.00%)   0/20 (0.00%)   0/20 (0.00%)   1/20 (5.00%) 
Infections and infestations             
Pneumonia * 1  0/20 (0.00%)  0/20 (0.00%)  0/20 (0.00%)  0/20 (0.00%)  0/20 (0.00%)  1/20 (5.00%) 
Injury, poisoning and procedural complications             
Animal bite * 1  0/20 (0.00%)  1/20 (5.00%)  0/20 (0.00%)  0/20 (0.00%)  0/20 (0.00%)  0/20 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 15.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Vi-CRM, Children Vi-PS, Children Vi-CRM, Older Infants PNC13, Older Infants Vi-CRM, Infants PNC13, Infants
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   14/20 (70.00%)   14/20 (70.00%)   17/20 (85.00%)   20/20 (100.00%)   20/20 (100.00%)   19/20 (95.00%) 
Gastrointestinal disorders             
Diarrhoea  1  3/20 (15.00%)  1/20 (5.00%)  6/20 (30.00%)  6/20 (30.00%)  4/20 (20.00%)  6/20 (30.00%) 
Vomiting  1  3/20 (15.00%)  0/20 (0.00%)  5/20 (25.00%)  4/20 (20.00%)  5/20 (25.00%)  5/20 (25.00%) 
General disorders             
Crying  1 [1]  0/20 (0.00%)  0/20 (0.00%)  1/20 (5.00%)  4/20 (20.00%)  13/20 (65.00%)  12/20 (60.00%) 
Induration  1  0/20 (0.00%)  0/20 (0.00%)  0/20 (0.00%)  0/20 (0.00%)  7/20 (35.00%)  3/20 (15.00%) 
Injection site erythema  1  1/20 (5.00%)  2/20 (10.00%)  5/20 (25.00%)  11/20 (55.00%)  12/20 (60.00%)  8/20 (40.00%) 
Injection site induration  1  2/20 (10.00%)  2/20 (10.00%)  1/20 (5.00%)  5/20 (25.00%)  14/20 (70.00%)  15/20 (75.00%) 
Injection site pain  1  6/20 (30.00%)  7/20 (35.00%)  3/20 (15.00%)  10/20 (50.00%)  20/20 (100.00%)  18/20 (90.00%) 
Irritability  1  1/20 (5.00%)  2/20 (10.00%)  2/20 (10.00%)  6/20 (30.00%)  12/20 (60.00%)  14/20 (70.00%) 
Pyrexia  1  3/20 (15.00%)  4/20 (20.00%)  7/20 (35.00%)  10/20 (50.00%)  7/20 (35.00%)  8/20 (40.00%) 
Immune system disorders             
Hypersensitivity * 1  0/20 (0.00%)  0/20 (0.00%)  0/20 (0.00%)  0/20 (0.00%)  2/20 (10.00%)  0/20 (0.00%) 
Infections and infestations             
Gastroenteritis * 1  0/20 (0.00%)  1/20 (5.00%)  2/20 (10.00%)  4/20 (20.00%)  6/20 (30.00%)  3/20 (15.00%) 
Impetigo * 1  2/20 (10.00%)  1/20 (5.00%)  0/20 (0.00%)  1/20 (5.00%)  0/20 (0.00%)  0/20 (0.00%) 
Mumps * 1  0/20 (0.00%)  0/20 (0.00%)  0/20 (0.00%)  2/20 (10.00%)  0/20 (0.00%)  0/20 (0.00%) 
Pneumonia * 1  2/20 (10.00%)  0/20 (0.00%)  6/20 (30.00%)  3/20 (15.00%)  4/20 (20.00%)  4/20 (20.00%) 
Respiratory tract infections * 1  0/20 (0.00%)  1/20 (5.00%)  1/20 (5.00%)  2/20 (10.00%)  3/20 (15.00%)  3/20 (15.00%) 
Rhinitis * 1  1/20 (5.00%)  0/20 (0.00%)  4/20 (20.00%)  3/20 (15.00%)  4/20 (20.00%)  5/20 (25.00%) 
Upper respiratory tract infection * 1  8/20 (40.00%)  7/20 (35.00%)  5/20 (25.00%)  6/20 (30.00%)  9/20 (45.00%)  10/20 (50.00%) 
Viral infection * 1  2/20 (10.00%)  0/20 (0.00%)  0/20 (0.00%)  0/20 (0.00%)  1/20 (5.00%)  0/20 (0.00%) 
Nervous system disorders             
Somnolence  1  0/20 (0.00%)  1/20 (5.00%)  2/20 (10.00%)  4/20 (20.00%)  8/20 (40.00%)  10/20 (50.00%) 
Psychiatric disorders             
Eating disorders  1  0/20 (0.00%)  2/20 (10.00%)  2/20 (10.00%)  8/20 (40.00%)  7/20 (35.00%)  9/20 (45.00%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 15.0
[1]
systemic assessment for older infants and infants
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
In the event that no publication of the Study results has been made by NVGH within twelve (12) months of Study database lock and no proposed publication is under discussion by the publication committee, Principal Investigator may publish its own Study results.
Results Point of Contact
Name/Title: Dr. Audino Podda
Organization: Novartis Vaccines Institute for Global Health
Phone: +39 0577 243496
Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT01437267     History of Changes
Other Study ID Numbers: H01_05TP
First Submitted: September 19, 2011
First Posted: September 20, 2011
Results First Submitted: March 5, 2014
Results First Posted: April 10, 2014
Last Update Posted: April 10, 2014