Study of Immunogenicity and Safety of a Booster Dose of DTaP-IPV-HB-PRP~T Combined Vaccine in Healthy Turkish Infants

• ClinicalTrials.gov Identifier: NCT00619502
• Recruitment Status: Completed
• First Posted: February 21, 2008
• Results First Posted: April 3, 2014
• Last Update Posted: May 13, 2016
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Conditions: Diphtheria; Polio; Pertussis; Hepatitis B
• Intervention: Biological: DTaP-IPV-HB-PRP~T vaccine
• Enrollment: 254

Participant Flow

Recruitment Details	Participants were enrolled from 14 December 2007 to 07 January 2008 at 1 clinical center in Turkey.
Pre-assignment Details	A total of 254 participants who met all inclusion, but no exclusion criteria were enrolled and vaccinated.

Arm/Group Title	DTaP-IPV-HepB-PRP~T	Pentaxim™ + Engerix B™
Arm/Group Description	All participants received a primary series of 3 vaccinations with DTaP-IPV-HepB-PRP~T, with 1 dose each at 2, 3, and 4 months of age, in Study A3L10; they received a booster dose of DTaP-IPV-HepB-PRP~T at 15 to 18 months of age in the present study.	All participants received a primary series of 3 vaccinations with Pentaxim™ and Engerix B™ vaccines, with 1 dose each at 2, 3, and 4 months of age, in Study A3L10; they received a booster dose of DTaP-IPV-Hep B-PRP~T at 15 to 18 months of age in the present study.
Period Title: Overall Study
Started	130	124
Completed	122	114
Not Completed	8	10
Reason Not Completed
Lost to Follow-up	8	10

Baseline Characteristics

Arm/Group Title		DTaP-IPV-HepB-PRP~T	Pentaxim™ + Engerix B™	Total
Arm/Group Description		All participants received a primary series of 3 vaccinations with DTaP-IPV-HepB-PRP~T, with 1 dose each at 2, 3, and 4 months of age, in Study A3L10; they received a booster dose of DTaP-IPV-HepB-PRP~T at 15 to 18 months of age in the present study.	All participants received a primary series of 3 vaccinations with Pentaxim™ and Engerix B™ vaccines, with 1 dose each at 2, 3, and 4 months of age, in Study A3L10; they received a booster dose of DTaP-IPV-Hep B-PRP~T at 15 to 18 months of age in the present study.	Total of all reporting groups
Overall Number of Baseline Participants		130	124	254
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	130 participants	124 participants	254 participants
	<=18 years	130 100.0%	124 100.0%	254 100.0%
	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%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Months
	Number Analyzed	130 participants	124 participants	254 participants
		17.6 (0.198)	17.6 (0.279)	17.6 (0.241)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	130 participants	124 participants	254 participants
	Female	56 43.1%	54 43.5%	110 43.3%
	Male	74 56.9%	70 56.5%	144 56.7%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Turkey	Number Analyzed	130 participants	124 participants	254 participants
		130	124	254

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Pre-booster Antibody Persistence and Booster Response to DTaP-IPV-Hep B-PRP~T After Primary Vaccination With Either DTaP-IPV-Hep B-PRP~T or Pentaxim™ + Engerix B Vaccine™
Description	Antibody titers measured by chemiluminescence detection for Hepatitis B (Hep B); Farr type radioimmunoassay for Haemophilus influenza type b (PRP); toxin neutralization for Diphtheria (D); indirect enzyme-linked immunosorbent assay (ELISA) for Tetanus (T); neutralization assay for Poliovirus types 1, 2, and 3; and ELISA for Pertussis toxoid (PT) and Filamentous hemagglutinin (FHA). Persistence and response: ≥ 10 mIU/mL for anti-Hep B, ≥ 0.15 µg/mL for anti-PRP, ≥ 0.01 IU/mL for anti-D and anti-T, ≥ 8 (1/dil) for anti-Poliovirus; and ≥ 4-fold increase from Day 0 for anti-PT and anti-FHA.
Time Frame	Day 0 before and Day 30 Post-booster vaccination

Outcome Measure Data

Analysis Population Description

Antibody titers were assessed in all participants with any immunogenicity data who did not have any protocol violations that might have interfered with primary criteria evaluation.

Arm/Group Title	DTaP-IPV-HepB-PRP~T	Pentaxim™ + Engerix B™
Arm/Group Description:	All participants received a primary series of 3 vaccinations with DTaP-IPV-HepB-PRP~T, with 1 dose each at 2, 3, and 4 months of age, in Study A3L10; they received a booster dose of DTaP-IPV-HepB-PRP~T at 15 to 18 months of age in the present study.	All participants received a primary series of 3 vaccinations with Pentaxim™ and Engerix B™ vaccines, with 1 dose each at 2, 3, and 4 months of age, in Study A3L10; they received a booster dose of DTaP-IPV-Hep B-PRP~T at 15 to 18 months of age in the present study.
Overall Number of Participants Analyzed	114	103
Measure Type: Number; Unit of Measure: Percentage of Participants
Anti-Hep B Pre-booster (N = 109, 103)	81	99
Anti-Hep B Post-booster (N = 111, 103)	97	100
Anti-PRP Pre-booster (N = 113,102)	85	83
Anti-PRP Post-booster (N = 114, 103)	100	100
Anti-Diphtheria Pre-booster (N = 104, 94)	90	88
Anti-Diphtheria Post-booster (N = 112, 98)	100	100
Anti-Tetanus Pre-booster (N = 97, 90)	100	100
Anti-Tetanus Post-booster (N = 109, 96)	100	100
Anti-Polio 1 Pre-booster (N = 88, 86)	99	99
Anti-Polio 1 Post-booster (N = 105, 87)	100	100
Anti-Polio 2 Pre-booster (N = 84, 87)	100	98
Anti-Polio 2 Post-booster (N = 101, 83)	100	100
Anti-Polio 3 Pre-booster (N = 88,86)	85	97
Anti-Polio 3 Post-booster (N = 102, 84)	100	100
Anti-PT Post-booster (N = 86, 79)	97	96
Anti-FHA Post-booster (N = 73,77)	92	97

2. Primary Outcome

Title	Geometric Mean Titers (GMTs) Before and After Booster Vaccination With DTaP-IPV-Hep B-PRP~T
Description	Antibody titers were measured by chemiluminescence detection for Hepatitis B (Hep B); Farr type radioimmunoassay for Haemophilus influenza type b (PRP); toxin neutralization test for Diphtheria (D); indirect enzyme-linked immunosorbent assay (ELISA) for Tetanus (T); neutralization assay for Poliovirus types 1, 2, and 3; and ELISA for Pertussis toxoid (PT) and Filamentous hemagglutinin (FHA).
Time Frame	Day 0 before and Day 30 post-booster vaccination

Outcome Measure Data

Analysis Population Description

GMTs were assessed in all participants with any immunogenicity data who did not have any protocol violations that might have interfered with primary criteria evaluation (Per Protocol Population).

Arm/Group Title	DTaP-IPV-HepB-PRP~T	Pentaxim™ + Engerix B™
Arm/Group Description:	All participants received a primary series of 3 vaccinations with DTaP-IPV-HepB-PRP~T, with 1 dose each at 2, 3, and 4 months of age, in Study A3L10; they received a booster dose of DTaP-IPV-HepB-PRP~T at 15 to 18 months of age in the present study.	All participants received a primary series of 3 vaccinations with Pentaxim™ and Engerix B™ vaccines, with 1 dose each at 2, 3, and 4 months of age, in Study A3L10; they received a booster dose of DTaP-IPV-Hep B-PRP~T at 15 to 18 months of age in the present study.
Overall Number of Participants Analyzed	114	103
Geometric Mean (95% Confidence Interval); Unit of Measure: Titers
Anti-Hep B Pre-booster (N = 109, 103)	44.2; (32.3 to 60.7)	223; (176 to 282)
Anti-Hep B Post-booster (N = 111, 103)	1379; (916 to 2078)	26189; (19133 to 35846)
Anti-PRP Pre-booster (N = 113, 102)	0.724; (0.541 to 0.968)	0.612; (0.443 to 0.844)
Anti-PRP Post-booster (N = 114, 103)	72.5; (55.8 to 94.3)	86.9; (69.8 to 108)
Anti-Diphtheria Pre-booster (N = 104, 94)	0.028; (0.022 to 0.035)	0.032; (0.024 to 0.041)
Anti-Diphtheria Post-booster (N = 112, 98)	5.09; (3.89 to 6.66)	10.2; (7.59 to 13.8)
Anti-Tetanus Pre-booster (N = 97, 90)	0.244; (0.204 to 0.292)	0.194; (0.158 to 0.238)
Anti-Tetanus Post-booster (N = 109, 96)	8.98; (7.52 to 10.7)	13.1; (10.8 to 15.8)
Anti-Polio 1 Pre-booster (N= 88, 86)	110; (81.6 to 148)	114; (82.4 to 157)
Anti-Polio 1 Post-booster (N = 105, 87)	5477; (4401 to 6814)	9050; (7134 to 11480)
Anti-Polio 2 Pre-booster (N = 84, 87)	114; (84.9 to 153)	131; (95.3 to 179)
Anti-Polio 2 Post-booster (N = 101, 83)	6099; (4916 to 7566)	9170; (7170 to 11727)
Anti-Polio 3 Pre-booster (N = 88, 86)	47.1; (33.1 to 67.1)	101; (73.0 to 141)
Anti-Polio 3 Post-booster (N = 102, 84)	5542; (4156 to 7392)	10152; (7806 to 13205)
Anti-PT Pre-booster (N = 86, 87)	6.08; (4.74 to 7.79)	7.49; (5.97 to 9.41)
Anti-PT Post-booster (N = 113, 95)	160; (137 to 187)	237; (202 to 278)
Anti-FHA Pre-booster (N = 74, 81)	12.5; (9.59 to 16.4)	8.18; (6.49 to 10.3)
Anti-FHA Post-booster (N = 111, 97)	222; (194 to 254)	234; (201 to 272)

3. Primary Outcome

Title	Number of Participants With Solicited Injection Site and Systemic Reactions After Booster Vaccination With DTaP-IPV-Hep B-PRP~T
Description	Solicited Injection Site Reactions: Pain, Erythema, Swelling, and Extensive Swelling of Vaccinated Limb. Solicited Systemic Reactions: Pyrexia (Temperature), Vomiting, Crying, Somnolence, Anorexia, and Irritability. Grade 3 defined as: Pain, cries when injected limb is moved or movement of limb reduced; Erythema and Swelling, ≥ 5 cm; Extensive Swelling of Vaccinated Limb, All; Pyrexia, ≥ 39ºC; Vomiting, ≥ 6 episodes/24 hours or requiring parenteral hydration; Crying > 3 hours; Somnolence, sleeping most of time or difficult to wake up; Anorexia, refuses ≥ 3 feeds or most feeds; Irritability, inconsolable.
Time Frame	Day 0 up to Day 7 post-booster vaccination

Outcome Measure Data

Analysis Population Description

Solicited reactions were assessed in all participants who received a booster dose of DTaP-IPV-Hep B-PRP~T according to the primary series received (Safety Analysis Population).

Arm/Group Title	DTaP-IPV-HepB-PRP-T	Pentaxim™ + Engerix B™
Arm/Group Description:	All participants received a primary series of 3 vaccinations with DTaP-IPV-HepB-PRP~T, with 1 dose each at 2, 3, and 4 months of age, in Study A3L10; they received a booster dose of DTaP-IPV-HepB-PRP-T at 15 to 18 months of age in the present study.	All participants received a primary series of 3 vaccinations with Pentaxim™ and Engerix B™ vaccines, with 1 dose each at 2, 3, and 4 months of age, in Study A3L10; they received a booster dose of DTaP-IPV-HepB-PRP-T at 15 to 18 months of age in the present study.
Overall Number of Participants Analyzed	121	111
Measure Type: Number; Unit of Measure: Participants
Pain	56	67
Grade 3 Pain	4	2
Erythema	35	50
Grade 3 Erythema	3	4
Swelling	26	36
Grade 3 Swelling	2	3
Extensive Swelling of Vaccinated Limb	0	0
Pyrexia	29	36
Grade 3 Pyrexia	1	0
Vomiting	13	11
Grade 3 Vomiting	2	2
Crying	29	35
Grade 3 Crying	3	4
Somnolence	24	25
Grade 3 Somnolence	2	3
Anorexia	40	43
Grade 3 Anorexia	9	8
Irritability	51	61
Grade 3 Irritability	5	7

Adverse Events

Time Frame	Adverse events data were collected from Day 0 after booster vaccination to up to 6 months after vaccination.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	DTaP-IPV-HepB-PRP~T		Pentaxim™ + Engerix B™
Arm/Group Description	All participants received a primary series of 3 vaccinations with DTaP-IPV-HepB-PRP~T, with 1 dose each at 2, 3, and 4 months of age, in Study A3L10; they received a booster dose of DTaP-IPV-HepB-PRP~T at 15 to 18 months of age in the present study.		All participants received a primary series of 3 vaccinations with Pentaxim™ and Engerix B™ vaccines, with 1 dose each at 2, 3, and 4 months of age, in Study A3L10; they received a booster dose of DTaP-IPV-Hep B-PRP~T at 15 to 18 months of age in the present study.
All-Cause Mortality
	DTaP-IPV-HepB-PRP~T		Pentaxim™ + Engerix B™
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	DTaP-IPV-HepB-PRP~T		Pentaxim™ + Engerix B™
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/130 (3.08%)		2/124 (1.61%)
Gastrointestinal disorders
Gastroesophageal reflux disease * 1	1/130 (0.77%)	1	0/124 (0.00%)	0
Infections and infestations
Bronchitis * 1	1/130 (0.77%)	1	0/124 (0.00%)	0
Gastroenteritis * 1	1/130 (0.77%)	1	1/124 (0.81%)	1
Gastroenteritis rotavirus * 1	0/130 (0.00%)	0	1/124 (0.81%)	1
Injury, poisoning and procedural complications
Poisoning * 1	1/130 (0.77%)	1	0/124 (0.00%)	0
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 9.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5.00%
	DTaP-IPV-HepB-PRP~T		Pentaxim™ + Engerix B™
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	56/130 (43.08%)		67/124 (54.03%)
Gastrointestinal disorders
Vomiting † 1	13/130 (10.00%)	13	11/124 (8.87%)	11
General disorders
Injection site erythema † 1	35/130 (26.92%)	35	50/124 (40.32%)	50
Injection site pain † 1	56/130 (43.08%)	56	67/124 (54.03%)	67
Injection site swelling † 1	26/130 (20.00%)	26	36/124 (29.03%)	36
Irritability † 1	51/130 (39.23%)	51	61/124 (49.19%)	61
Pyrexia † 1	29/130 (22.31%)	29	36/124 (29.03%)	36
Metabolism and nutrition disorders
Anorexia † 1	40/130 (30.77%)	40	43/124 (34.68%)	43
Nervous system disorders
Somnolence † 1	24/130 (18.46%)	24	25/124 (20.16%)	25
Psychiatric disorders
Crying † 1	29/130 (22.31%)	29	35/124 (28.23%)	35
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 9.0

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: NCT00619502
• Other Study ID Numbers: A3L22
• First Submitted: February 11, 2008
• First Posted: February 21, 2008
• Results First Submitted: February 22, 2014
• Results First Posted: April 3, 2014
• Last Update Posted: May 13, 2016