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Study of DTaP-IPV-Hep B-PRP~T Combined Vaccine in Indian Infants Previously Given a Dose of Hepatitis B Vaccine at Birth

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ClinicalTrials.gov Identifier: NCT01948193
Recruitment Status : Completed
First Posted : September 23, 2013
Results First Posted : September 25, 2015
Last Update Posted : October 20, 2015
Sponsor:
Information provided by (Responsible Party):
Sanofi ( Sanofi Pasteur, a Sanofi Company )

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Prevention
Conditions Diphtheria
Tetanus
Whooping Cough
Hepatitis B
Poliomyelitis
Invasive Hib Infections
Intervention Biological: Hexaxim™: DTaP-IPV-Hep B-PRP~T combined vaccine
Enrollment 177
Recruitment Details Study participants were enrolled from 19 February 2014 to 30 June 2014 at 2 clinical sites in India.
Pre-assignment Details A total of 177 participants who met all of the inclusion criteria and none of the exclusion criteria were enrolled and vaccinated.
Arm/Group Title All Infants
Hide Arm/Group Description Infants aged 6 to 8 weeks received 3 injections of Sanofi Pasteur’s DTaP IPV HB PRP T combined vaccine at 6, 10 and 14 weeks of age following a documented dose of a commercial oral poliovirus vaccine and recombinant Hepatitis B monovalent vaccine at birth.
Period Title: Overall Study
Started 177
Completed 168
Not Completed 9
Reason Not Completed
Serious event             2
Lost to Follow-up             7
Arm/Group Title All Infants
Hide Arm/Group Description Infants aged 6 to 8 weeks received 3 injections of Sanofi Pasteur’s DTaP-IPV-HB-PRP-T combined vaccine at 6, 10 and 14 weeks of age following a documented dose of a commercial oral poliovirus vaccine and recombinant Hepatitis B monovalent vaccine at birth.
Overall Number of Baseline Participants 177
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 177 participants
<=18 years
177
 100.0%
Between 18 and 65 years
0
   0.0%
>=65 years
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Weeks
Number Analyzed 177 participants
6.9  (0.6)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 177 participants
Female
78
  44.1%
Male
99
  55.9%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
India Number Analyzed 177 participants
177
1.Primary Outcome
Title Percentage of Participants With Seroprotection After Vaccinations With Sanofi Pasteur’s DTaP-IPV-HB-PRP-T Combined Vaccine Following a Documented Dose of a Commercial Oral Poliovirus Vaccine and Recombinant Hep B Monovalent Vaccine at Birth
Hide Description

Diphtheria antibodies were measured by a toxin neutralization test, tetanus antibodies by an enzyme-linked immunosorbent assay (ELISA), Haemophilus influenzae type b polysaccharide (PRP) antibodies by Farr type radioimmunoassay, poliovirus 1, 2, and 3 antibodies by a neutralization assay, and Hepatitis B (Hep B) antibodies were measured by VITROS ECi/ECiQ Immunodiagnostic System.

Description of seroprotection: Diphtheria and Tetanus antibody concentrations ≥0.01 International Units (IU)/mL; Poliovirus 1, 2, and 3 titers ≥8 (1/dilution); Hep B concentrations ≥10 mIU/mL, and PRP ≥0.15 µg/mL.

Time Frame Pre-dose 1 to one month post-dose 3
Hide Outcome Measure Data
Hide Analysis Population Description
Seroprotection was assessed in the Per-protocol Analysis Set.
Arm/Group Title All Infants
Hide Arm/Group Description:
Infants aged 6 to 8 weeks received 3 injections of Sanofi Pasteur’s DTaP-IPV-HB-PRP-T combined vaccine at 6, 10 and 14 weeks of age following a documented dose of a commercial oral poliovirus vaccine and recombinant Hepatitis B monovalent vaccine at birth.
Overall Number of Participants Analyzed 156
Measure Type: Number
Unit of Measure: Percentage of participants
Anti-Diphtheria; Post-dose 3; ≥0.01, (N=135) 99.3
Anti-Tetanus; Post-dose 3, ≥0.01 (N=134) 100
Anti-Polio 1; Post-dose 3 (N=145) 100
Anti-Polio 2; Post-dose 3 (N=146) 100
Anti-Polio 3; Post-dose 3 (N=144) 100
Anti-Hep B; Post-dose 3, ≥10 (N=152) 100
Anti-PRP; Post-dose 3, ≥0.15 (N=156) 100
2.Primary Outcome
Title Percentage of Participants With Vaccine Response After Vaccinations With Sanofi Pasteur’s DTaP-IPV-HB-PRP-T Combined Vaccine Following a Documented Dose of a Commercial Oral Poliovirus Vaccine and Recombinant Hep B Monovalent Vaccine at Birth
Hide Description Anti-pertussis toxin (PT) and anti-filamentous hemagglutinin (FHA) antibodies were measured with an ELISA. Vaccine response was defined as percentage of participants with post-dose 3 anti-PT and anti-FHA antibody concentrations in ELISA units (EU)/mL ≥ 4 x Lower Limit of Quantification (LLOQ) if pre-vaccination concentration was < 4 x LLOQ or ≥ pre-vaccination concentration if pre-vaccination concentrations ≥ 4 x LLOQ.
Time Frame Pre-dose 1 to one month post-dose 3
Hide Outcome Measure Data
Hide Analysis Population Description
Vaccine response was assessed in the Per-protocol Analysis Set.
Arm/Group Title All Infants
Hide Arm/Group Description:
Infants aged 6 to 8 weeks received 3 injections of Sanofi Pasteur’s DTaP-IPV-HB-PRP-T combined vaccine at 6, 10 and 14 weeks of age following a documented dose of a commercial oral poliovirus vaccine and recombinant Hepatitis B monovalent vaccine at birth.
Overall Number of Participants Analyzed 156
Measure Type: Number
Unit of Measure: Percentage of participants
Anti-PT; Pre-dose 1 (N=147) 59.9
Anti-PT; Vaccine response (N=146) 93.8
Anti-PT; ≥4-fold increase (N=146) 88.4
Anti-FHA; Pre-dose 1 (N=151) 88.7
Anti-FHA; Vaccine response (N=147) 99.3
Anti-FHA; ≥4-fold increase (N=147) 90.5
3.Secondary Outcome
Title Percentage of Participants With Seroprotection Before and After Vaccinations With Sanofi Pasteur’s DTaP-IPV-HB-PRP-T Combined Vaccine Following a Documented Dose of a Commercial Oral Poliovirus Vaccine and Recombinant Hep B Monovalent Vaccine at Birth
Hide Description

Diphtheria antibodies were measured by a toxin neutralization test, tetanus antibodies by an enzyme-linked immunosorbent assay (ELISA), Haemophilus influenzae type b polysaccharide (PRP) antibodies by Farr type radioimmunoassay, poliovirus 1, 2, and 3 antibodies by a neutralization assay, and Hepatitis B (Hep B) antibodies were measured by VITROS ECi/ECiQ Immunodiagnostic System.

Description of seroprotection: Diphtheria and Tetanus antibody concentrations ≥0.01 International Units (IU)/mL; Poliovirus 1, 2, and 3 titers ≥8 (1/dilution); Hep B concentrations ≥10 mIU/mL, and PRP ≥0.15 µg/mL.

Time Frame Pre-dose 1 to one month post-dose 3
Hide Outcome Measure Data
Hide Analysis Population Description
Seroprotection was assessed in the Per-protocol Analysis Set.
Arm/Group Title All Infants
Hide Arm/Group Description:
Infants aged 6 to 8 weeks received 3 injections of Sanofi Pasteur’s DTaP-IPV-HB-PRP-T combined vaccine at 6, 10 and 14 weeks of age following a documented dose of a commercial oral poliovirus vaccine and recombinant Hepatitis B monovalent vaccine at birth.
Overall Number of Participants Analyzed 156
Measure Type: Number
Unit of Measure: Percentage of participants
Anti-Diphtheria; Pre-dose, 1 ≥0.01 (N=152) 67.1
Anti-Diphtheria; Pre-dose 1, ≥0.1 (N=152) 15.8
Anti-Diphtheria; Post-dose 3; ≥0.01, (N=135) 99.3
Anti-Diphtheria; Post-dose 3; ≥0.1 (N=135) 49.6
Anti-Diphtheria; Post-dose 3, ≥1.0 (N=135) 5.2
Anti-Tetanus; Post-dose 3, ≥0.01 (N=134) 100.0
Anti-Tetanus; Post-dose 3, ≥0.1 (N=134) 100.0
Anti-Tetanus; Post-dose 3, ≥1.0 (N=134) 84.3
Anti-Polio 1; Post-dose 3 (N=145) 100.0
Anti-Polio 2; Post-dose 3 (N=146) 100.0
Anti-Polio 3; Post-dose 3 (N=144) 100.0
Anti-Hep B; Pre-dose 1, ≥10 (N=152) 13.2
Anti-Hep B; Post-dose 3, ≥10 (N=152) 100.0
Anti-Hep B; Post-dose 3, ≥100 (N=152) 99.3
Anti-PRP; Post-dose 3, ≥0.15 (N=156) 100.0
Anti-PRP; Post-dose 3, ≥1.0 (N=156) 93.6
4.Secondary Outcome
Title Geometric Mean Titers of Antibodies Against Vaccine Antigens After Vaccinations With Sanofi Pasteur’s DTaP-IPV-HB-PRP-T Combined Vaccine After a Documented Dose of an Oral Poliovirus Vaccine and Recombinant Hep B Monovalent Vaccine at Birth
Hide Description Diphtheria antibodies were measured by a toxin neutralization test, tetanus, PT, and FHA antibodies by an ELISA, PRP antibodies by a Farr type radioimmunoassay, poliovirus 1, 2, and 3 antibodies by a neutralization assay, and Hep B antibodies were measured by VITROS ECi/ECiQ Immunodiagnostic System.
Time Frame Pre-dose 1 to one month post-dose 3
Hide Outcome Measure Data
Hide Analysis Population Description
Geometric mean titers were assessed in the Per-protocol Analysis Set.
Arm/Group Title All Infants
Hide Arm/Group Description:
Infants aged 6 to 8 weeks received 3 injections of Sanofi Pasteur’s DTaP-IPV-HB-PRP-T combined vaccine at 6, 10 and 14 weeks of age following a documented dose of a commercial oral poliovirus vaccine and recombinant Hepatitis B monovalent vaccine at birth.
Overall Number of Participants Analyzed 156
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
Anti-Diphtheria; Pre-dose 1 (N=152)
0.019
(0.015 to 0.025)
Anti-Diphtheria; Post-dose 3 (N=135)
0.120
(0.099 to 0.146)
Anti-Tetanus; Post-dose 3 (N=134)
1.95
(1.75 to 2.17)
Anti-PT; Pre-dose 1 (N=147)
3.84
(3.00 to 4.91)
Anti-PT; Post-dose 3 (N=155)
191
(173 to 210)
Anti-FHA; Pre-dose 1 (N=151)
6.17
(5.10 to 7.48)
Anti-FHA; Post-dose 3 (N=152)
226
(208 to 247)
Anti-Polio 1; Post-dose 3 (N=145)
1124
(861 to 1468)
Anti-Polio 2; Post-dose 3 (N=146)
1401
(1108 to 1771)
Anti-Polio 3; Post-dose 3 (N=144)
2019
(1672 to 2437)
Anti-Hep B; Pre-dose 1 (N=152)
3.78
(3.23 to 4.43)
Anti-Hep B; Post-dose 3 (N=152)
2491
(2073 to 2995)
Anti-PRP; Post-dose 3 (N=156)
7.86
(6.35 to 9.73)
5.Secondary Outcome
Title Geometric Mean Titer Ratios of Antibodies Against Vaccine Antigens After Vaccinations With Sanofi Pasteur’s DTaP-IPV-HB-PRP-T Combined Vaccine After a Documented Dose of Oral Poliovirus Vaccine and Recombinant Hep B Monovalent Vaccine at Birth
Hide Description Diphtheria antibodies were measured by a toxin neutralization test, PT and FHA antibodies by an ELISA, and Hep B antibodies were measured by VITROS ECi/ECiQ Immunodiagnostic System.
Time Frame Pre-dose 1 to one month post-dose 3
Hide Outcome Measure Data
Hide Analysis Population Description
Geometric mean titer ratios were assessed in the Per-protocol Analysis Set.
Arm/Group Title All Infants
Hide Arm/Group Description:
Infants aged 6 to 8 weeks received 3 injections of Sanofi Pasteur’s DTaP-IPV-HB-PRP-T combined vaccine at 6, 10 and 14 weeks of age following a documented dose of a commercial oral poliovirus vaccine and recombinant Hepatitis B monovalent vaccine at birth.
Overall Number of Participants Analyzed 156
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titer ratio
Anti-Diphtheria (N=131)
5.85
(3.93 to 8.72)
Anti-PT (N=146)
50.7
(37.3 to 69.0)
Anti-FHA (N=147)
36.6
(28.6 to 46.8)
Anti-Hep B (N=149)
686
(542 to 870)
6.Secondary Outcome
Title Percentage of Participants Reporting Solicited Injection-site or Systemic Reaction After Each Vaccination With Sanofi Pasteur’s DTaP-IPV-HB-PRP-T Combined Vaccine Following a Documented Dose of Oral Poliovirus and Recombinant Hep B Vaccine at Birth
Hide Description Injection-site reactions: Tenderness, Erythema, and Swelling. Systemic reactions: Fever, Vomiting, Crying abnormal, Drowsiness, Appetite lost, and Irritability. Grade 3 Injection site reactions: Tenderness, Cries when injected limb is moved, or reduced movement of injected limb; Erythema and Swelling, ≥50 mm. Grade 3 Systemic reactions: Fever, >39.5°C or >103.1°F; Vomiting, ≥6 episodes/24 hours or requires parenteral hydration; Crying abnormal, >3 hours; Drowsiness, Sleeping most of the time/difficult to wake up; Appetite lost, Refuses ≥3 or most feeds/meals; Irritability, Inconsolable.
Time Frame Within 7 days after each vaccine injection
Hide Outcome Measure Data
Hide Analysis Population Description
Solicited injection-site and systemic reactions were assessed in the Safety Analysis Set.
Arm/Group Title All Infants
Hide Arm/Group Description:
Infants aged 6 to 8 weeks received 3 injections of Sanofi Pasteur’s DTaP IPV HB PRP T combined vaccine at 6, 10 and 14 weeks of age following a documented dose of a commercial oral poliovirus vaccine and recombinant Hepatitis B monovalent vaccine at birth.
Overall Number of Participants Analyzed 177
Measure Type: Number
Unit of Measure: Percentage of participants
Any Injection-site Tenderness; Post Inj. 1 (N=174) 19.0
Grade 3 Inj. site Tenderness; Post Inj 1 (N=174) 2.3
Any Injection-site Erythema; Post Inj. 1 (N=174) 4.6
Grade 3 Inj. site Erythema; Post Inj. 1 (N=174) 0.0
Any Injection-site Swelling; Post Inj. 1 (N=174) 10.3
Grade 3 Inj. site Swelling; Post Inj. 1 (N=174) 0.0
Any Injection-site Tenderness; Post Inj. 2 (N=174) 13.8
Grade 3 Inj.-site Tenderness; Post Inj. 2 (N=174) 1.1
Any Injection-site Erythema; Post Inj. 2 (N=174) 3.4
Grade 3 Inj. site Erythema; Post Inj. 2 (N=174) 0.0
Any Injection-site Swelling; Post Inj. 2 (N=174) 3.4
Grade 3 Inj. site Swelling; Post Inj. 2 (N=174) 0.0
Any Injection-site Tenderness; Post Inj. 3 (N=168) 11.9
Grade 3 Inj. site Tenderness; Post Inj. 3 (N=168) 0.0
Any Injection-site Erythema; Post Inj. 3 (N=168) 0.6
Grade 3 Inj. site Erythema; Post Inj. 3 (N=168) 0.0
Any Injection-site Swelling; Post Inj. 3 (N=168) 6.5
Grade 3 Inj. site Swelling; Post Inj. 3 (N=168) 0.0
Any Fever; Post-injection 1 (N=174) 7.5
Grade 3 Fever; Post-injection 1 (N=174) 0.0
Any Vomiting; Post-injection 1 (N=174) 9.8
Grade 3 Vomiting; Post-injection 1 (N=174) 0.0
Any Crying abnormal; Post-injection 1 (N=174) 16.1
Grade 3 Crying abnormal; Post-injection 1 (N=174) 1.1
Any Drowsiness; Post injection 1 (N=174) 9.8
Grade 3 Drowsiness; Post Inj. 1 (N=174) 1.1
Any Appetite lost; Post Inj. 1 (N=174) 6.9
Grade 3 Appetite lost; Post Inj. 1 (N=174) 0.0
Any Irritability; Post Inj. 1 (N=174) 22.4
Grade 3 Irritability; Post Inj. 1 (N=174) 0.6
Any Fever; Post Inj. 2 (N=174) 8.6
Grade 3 Fever; Post Inj. 2 (N=174) 0.0
Any Vomiting; Post Inj. 2 (N=174) 3.4
Grade 3 Vomiting; Post Inj. 2 (N=174) 0.0
Any Crying abnormal; Post Inj. 2 (N=174) 9.8
Grade 3 Crying abnormal; Post Inj. 2 (N=174) 0.0
Any Drowsiness; Post Inj. 2 (N=174) 3.4
Grade 3 Drowsiness; Post Inj. 2 (N=174) 0.0
Any Appetite lost; Post Inj. 2 (N=174) 3.4
Grade 3 Appetite lost; Post Inj. 2 (N=174) 0.0
Any Irritability; Post Inj. 2 (N=174) 16.7
Grade 3 Irritability; Post Inj. 2 (N=174) 0.0
Any Fever; Post Inj. 3 (N=168) 7.1
Grade 3 Fever; Post Inj. 3 (N=168) 0.0
Any Vomiting; Post Inj. 3 (N=168) 3.0
Grade 3 Vomiting; Post Inj. 3 (N=168) 0.0
Any Crying abnormal; Post Inj. 3 (N=168) 7.7
Grade 3 Crying abnormal; Post Inj. 3 (N=168) 0.0
Any Drowsiness; Post Inj. 3 (N=168) 3.0
Grade 3 Drowsiness; Post Inj. 3 (N=168) 0.0
Any Appetite lost; Post Inj. 3 (N=168) 3.0
Grade 3 Appetite lost; Post Inj. 3 (N=168) 0.0
Any Irritability; Post Inj. 3 (N=168) 12.5
Grade 3 Irritability; Post Inj. 3 (N=168) 0.0
Time Frame Adverse event data were collected following first vaccination up to Day 30 post-dose 3.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title All Infants
Hide Arm/Group Description Infants aged 6 to 8 weeks received 3 injections of Sanofi Pasteur’s DTaP IPV HB PRP T combined vaccine at 6, 10 and 14 weeks of age following a documented dose of a commercial oral poliovirus vaccine and recombinant Hepatitis B monovalent vaccine at birth.
All-Cause Mortality
All Infants
Affected / at Risk (%)
Total   --/--    
Show Serious Adverse Events Hide Serious Adverse Events
All Infants
Affected / at Risk (%) # Events
Total   3/177 (1.69%)    
General disorders   
Death unexplained * 1  1/177 (0.56%)  1
Infections and infestations   
Bronchopneumonia * 1  1/177 (0.56%)  1
Septic shock * 1  1/177 (0.56%)  1
Nervous system disorders   
Epilepsy * 1  1/177 (0.56%)  1
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5.00%
All Infants
Affected / at Risk (%) # Events
Total   39/177 (22.03%)    
Gastrointestinal disorders   
Diarrhoea * 1  9/177 (5.08%)  9
Vomiting  1  17/174 (9.77%)  17
General disorders   
Injection site Tenderness  1  33/174 (18.97%)  33
Injection site Erythema  1  8/174 (4.60%)  8
Injection site Swelling  1  18/174 (10.34%)  18
Fever  1  15/174 (8.62%)  15
Infections and infestations   
Upper respiratory tract infection * 1  21/177 (11.86%)  24
Metabolism and nutrition disorders   
Appetite lost  1  12/174 (6.90%)  12
Nervous system disorders   
Drowsiness  1  17/174 (9.77%)  17
Psychiatric disorders   
Crying abnormal  1  28/174 (16.09%)  28
Irritability  1  39/174 (22.41%)  39
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA 11.0
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.
Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Sanofi Pasteur Inc.
EMail: RegistryContactUs@sanofipasteur.com
Layout table for additonal information
Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
ClinicalTrials.gov Identifier: NCT01948193     History of Changes
Other Study ID Numbers: A3L33
U1111-1127-6936 ( Other Identifier: WHO )
CTRI/2013/09/003997 ( Registry Identifier: Clinical Trial Registry India )
First Submitted: September 18, 2013
First Posted: September 23, 2013
Results First Submitted: August 26, 2015
Results First Posted: September 25, 2015
Last Update Posted: October 20, 2015