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

• 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: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

• Study Type: Interventional
• Study Design: Allocation: N/A; 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

Participant Flow

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
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

Baseline Characteristics

Arm/Group Title		All Infants
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
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

Outcome Measures

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
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

Outcome Measure Data

Analysis Population Description

Seroprotection was assessed in the Per-protocol Analysis Set.

Arm/Group Title	All Infants
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
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

Outcome Measure Data

Analysis Population Description

Vaccine response was assessed in the Per-protocol Analysis Set.

Arm/Group Title	All Infants
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
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

Outcome Measure Data

Analysis Population Description

Seroprotection was assessed in the Per-protocol Analysis Set.

Arm/Group Title	All Infants
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
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

Outcome Measure Data

Analysis Population Description

Geometric mean titers were assessed in the Per-protocol Analysis Set.

Arm/Group Title	All Infants
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
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

Outcome Measure Data

Analysis Population Description

Geometric mean titer ratios were assessed in the Per-protocol Analysis Set.

Arm/Group Title	All Infants
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
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

Outcome Measure Data

Analysis Population Description

Solicited injection-site and systemic reactions were assessed in the Safety Analysis Set.

Arm/Group Title	All Infants
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

Adverse Events

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
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	--/--
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
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

Limitations and Caveats

[Not Specified]

More Information

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

• Name/Title: Medical Director
• Organization: Sanofi Pasteur Inc.
• EMail: RegistryContactUs@sanofipasteur.com

• Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
• ClinicalTrials.gov Identifier: NCT01948193
• 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