Immunogenicity Study of Antibody Persistence and Booster Effect of PENTAXIM™ at 18 Months in Healthy Argentinean Infants

• ClinicalTrials.gov Identifier: NCT00303316
• Recruitment Status: Completed
• First Posted: March 16, 2006
• Results First Posted: February 22, 2013
• Last Update Posted: February 22, 2013
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Conditions: Diphtheria; Tetanus; Pertussis; Poliomyelitis; Hepatitis B
• Intervention: Biological: DTaP-IPV//PRP~T combined vaccine
• Enrollment: 458

Participant Flow

Recruitment Details	Participants were enrolled from 15 February 2006 to 03 October 2006 at 1 clinical center in Argentina.
Pre-assignment Details	A total of 458 participants who met all the inclusion and none of the exclusion criteria were enrolled and vaccinated.

Arm/Group Title	DTacP-IPV-Hep B-PRP~T Group	PENTAXIM™ and ENGERIX B® Group
Arm/Group Description	Participants received a booster dose of PENTAXIM™ at 18 months of age in this study. They had received 3 primary-series doses of Diphtheria (D), Tetanus (T), Pertussis (acellular component [aP]), hepatitis B (Hep B [recombinant DNA]) and poliomyelitis (Inactivated [IPV]), and Haemophilus influenzae type b (Hib) conjugated vaccine adsorbed (DTaP-IPV-HepB-PRP~T), (1 dose each at 2, 4, and 6 months of age) in Study A3L02 (NCT00831311).	Participants received a booster dose of PENTAXIM™ at 18 months of age in this study. They had received 3 primary-series doses of PENTAXIM™ and ENGERIX B® PEDIATRICO (1 dose each at 2, 4, and 6 months of age) in Study A3L02 (NCT00831311).
Period Title: Overall Study
Started	232	226
Completed	230	223
Not Completed	2	3
Reason Not Completed
Protocol Violation	1	0
Lost to Follow-up	0	1
Withdrawal by Subject	1	2

Baseline Characteristics

Arm/Group Title		DTacP-IPV-Hep B-PRP~T Group	PENTAXIM™ and ENGERIX B® Group	Total
Arm/Group Description		Participants received a booster dose of PENTAXIM™ at 18 months of age in this study. They had received 3 primary-series doses of Diphtheria (D), Tetanus (T), Pertussis (acellular component [aP]), hepatitis B (Hep B [recombinant DNA]) and poliomyelitis (Inactivated [IPV]), and Haemophilus influenzae type b (Hib) conjugated vaccine adsorbed (DTaP-IPV-HepB-PRP~T), (1 dose each at 2, 4, and 6 months of age) in Study A3L02 (NCT00831311).	Participants received a booster dose of PENTAXIM™ at 18 months of age in this study. They had received 3 primary-series doses of PENTAXIM™ and ENGERIX B® PEDIATRICO (1 dose each at 2, 4, and 6 months of age) in Study A3L02 (NCT00831311).	Total of all reporting groups
Overall Number of Baseline Participants		232	226	458
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	232 participants	226 participants	458 participants
	<=18 years	232 100.0%	226 100.0%	458 100.0%
	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	232 participants	226 participants	458 participants
		17.6 (0.436)	17.7 (0.492)	17.6 (0.465)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	232 participants	226 participants	458 participants
	Female	107 46.1%	107 47.3%	214 46.7%
	Male	125 53.9%	119 52.7%	244 53.3%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Argentina	Number Analyzed	232 participants	226 participants	458 participants
		232	226	458

Outcome Measures

1. Primary Outcome

Title	Summary of Antibody Persistence at 18 Months of Age in Participants That Received Primary Series Vaccination of Either DTaP-IPV-HepB-PRP~T or PENTAXIM™ and ENGERIX B® PEDIATRICO at 2, 4, and 6 Months of Age.
Description	Antibody persistence (pre-booster) were defined as titers ≥ 10 mIU/mL for hepatitis B (Hep B;); ≥ 0.15 µg/mL for Haemophilus influenzae type b (PRP); ≥ 0.01 IU/mL for Diphtheria and Tetanus; ≥ 8 (1/dil) for polio types 1, 2, and 3; and ≥ 4 EU/mL for Pertussis Toxoid (PT) and Filamentous Hemagglutinin (FHA).
Time Frame	Day 0 (Before booster vaccination)

Outcome Measure Data

Analysis Population Description

Antibody Persistence was assessed in all enrolled participants with pre-booster vaccination data (Intent-to-Treat population).

Arm/Group Title	DTacP-IPV-Hep B-PRP~T Group	PENTAXIM™ and ENGERIX B® Group
Arm/Group Description:	Participants received a booster dose of PENTAXIM™ at 18 months of age in this study. They had received 3 primary-series doses of Diphtheria (D), Tetanus (T), Pertussis (acellular component [aP]), hepatitis B (Hep B [recombinant DNA]) and poliomyelitis (Inactivated [IPV]), and Haemophilus influenzae type b (Hib) conjugated vaccine adsorbed (DTaP-IPV-HepB-PRP~T), (1 dose each at 2, 4, and 6 months of age) in Study A3L02 (NCT00831311).	Participants received a booster dose of PENTAXIM™ at 18 months of age in this study. They had received 3 primary-series doses of PENTAXIM™ and ENGERIX B® PEDIATRICO (1 dose each at 2, 4, and 6 months of age) in Study A3L02 (NCT00831311).
Overall Number of Participants Analyzed	232	226
Measure Type: Number; Unit of Measure: Participants
Anti-Hepatitis B (N = 228, 222)	195	221
Anti-PRP (N = 224, 217)	171	164
Anti-Diphtheria (N = 228, 221)	169	165
Anti-Tetanus (N = 229, 216)	229	216
Anti-Polio 1 (N = 214, 205)	213	205
Anti-Polio 2 (N = 217, 204)	215	203
Anti-Polio 3 (N = 214, 203)	205	199
Anti-Pertussis Toxoid (N= 216, 212)	190	190
Anti-Filamentous Hemagglutinin (N = 230, 220)	228	213

2. Primary Outcome

Title	Summary of Booster Response in Participants at 18 Months of Age Following Booster Vaccination With PENTAXIM™ Following a Primary Series Vaccination of Either DTaP-IPV-HepB-PRP~T or PENTAXIM™ and ENGERIX B® PEDIATRICO at 2, 4, and 6 Months of Age.
Description	Booster response were defined as titers ≥ 1.0 µg/mL for Haemophilus influenzae type b (PRP); ≥ 0.1 IU/mL for Diphtheria and Tetanus; ≥ 8 (1/dil) for Polio types 1, 2, and 3; and for Pertussis Toxoid (PT) and Filamentous Hemagglutinin (FHA) ≥ 4 EU/mL and a ≥ 4 fold increase from pre-booster to post-booster value.
Time Frame	Day 30 Post-booster Vaccination

Outcome Measure Data

Analysis Population Description

Booster responses were assessed in all vaccinated participants with endpoint data following the booster vaccination (Intent-to-Treat population).

Arm/Group Title	DTacP-IPV-Hep B-PRP~T Group	PENTAXIM™ and ENGERIX B® Group
Arm/Group Description:	Participants received a booster dose of PENTAXIM™ at 18 months of age in this study. They had received 3 primary-series doses of Diphtheria (D), Tetanus (T), Pertussis (acellular component [aP]), hepatitis B (Hep B [recombinant DNA]) and poliomyelitis (Inactivated [IPV]), and Haemophilus influenzae type b (Hib) conjugated vaccine adsorbed (DTaP-IPV-HepB-PRP~T), (1 dose each at 2, 4, and 6 months of age) in Study A3L02 (NCT00831311).	Participants received a booster dose of PENTAXIM™ at 18 months of age in this study. They had received 3 primary-series doses of PENTAXIM™ and ENGERIX B® PEDIATRICO (1 dose each at 2, 4, and 6 months of age) in Study A3L02 (NCT00831311).
Overall Number of Participants Analyzed	232	226
Measure Type: Number; Unit of Measure: Participants
Anti-PRP (N = 223, 216)	220	215
Anti-Diphtheria (N = 225, 221)	216	214
Anti-Tetanus (N = 222, 219)	222	219
Anti-Polio 1 (N = 211, 209)	211	209
Anti-Polio 2 (N = 208, 210)	208	210
Anti-Polio 3 (N = 205, 205)	205	205
Anti-Pertussis Toxoid (N = 226, 220)	226	220
Anti-Pertussis Toxoid (4-Fold Rise: N = 211, 208)	202	199
Anti-Filamentous Hemagglutinin (N = 227, 221)	227	221
Anti-FHA (4-Fold Rise: N = 225, 215)	198	202

3. Primary Outcome

Title	Geometric Mean Titers (GMTs) of Antibodies Before and After Booster Vaccination With PENTAXIM™ Following a Primary Series Vaccination of Either DTaP-IPV-HepB-PRP~T or PENTAXIM™ and ENGERIX B® PEDIATRICO at 2, 4, and 6 Months of Age.
Description	Antibody titers determination: Hepatitis B (Hep B) by enhanced chemiluminescence assay; Haemophilus influenzae type b (PRP), Tetanus, Pertussis toxoid (PT) and filamentous hemagglutinin (FHA) by enzyme linked immunosorbent assay (ELISA); Diphtheria by neutralization test; Poliovirus types 1,2, and 3 by microneutralization assay.
Time Frame	Day 0 (pre-booster) and Day 30 post-booster

Outcome Measure Data

Analysis Population Description

Geometric mean titers were assessed in all participants with endpoint data who received the booster vaccine (Intent-to-Treat Analysis Set for immunogenicity).

Arm/Group Title	DTacP-IPV-Hep B-PRP~T Group	PENTAXIM™ and ENGERIX B® Group
Arm/Group Description:	Participants received a booster dose of PENTAXIM™ at 18 months of age in this study. They had received 3 primary-series doses of Diphtheria (D), Tetanus (T), Pertussis (acellular component [aP]), hepatitis B (Hep B [recombinant DNA]) and poliomyelitis (Inactivated [IPV]), and Haemophilus influenzae type b (Hib) conjugated vaccine adsorbed (DTaP-IPV-HepB-PRP~T), (1 dose each at 2, 4, and 6 months of age) in Study A3L02 (NCT00831311).	Participants received a booster dose of PENTAXIM™ at 18 months of age in this study. They had received 3 primary-series doses of PENTAXIM™ and ENGERIX B® PEDIATRICO (1 dose each at 2, 4, and 6 months of age) in Study A3L02 (NCT00831311).
Overall Number of Participants Analyzed	232	226
Geometric Mean (95% Confidence Interval); Unit of Measure: Titers
Anti-Hepatitis B Pre-booster (N = 228, 222)	87.6; (69.2 to 111)	197; (168 to 230)
Anti-PRP Pre-booster (N = 224, 217)	0.399; (0.327 to 0.487)	0.326; (0.270 to 0.394)
Anti-PRP Post-booster (N = 223, 216)	27.4; (23.0 to 32.7)	41.4; (35.0 to 48.8)
Anti-Diphtheria Pre-booster (N = 228, 221)	0.022; (0.018 to 0.027)	0.018; (0.015 to 0.022)
Anti-Diphtheria Post-booster (N = 225, 221)	1.92; (1.58 to 2.32)	2.11; (1.74 to 2.56)
Anti-Tetanus Pre-booster (N = 229, 216)	0.287; (0.255 to 0.325)	0.171; (0.153 to 0.192)
Anti-Tetanus Post-booster (N = 222, 219)	4.81; (4.37 to 5.31)	4.54; (4.07 to 5.08)
Anti-Polio 1 Pre-booster (N= 214, 205)	303; (251 to 365)	232; (193 to 279)
Anti-Polio 1 Post-booster (N = 211, 209)	7243; (6218 to 8436)	9996; (8521 to 11725)
Anti-Polio 2 Pre-booster (N = 217, 204)	370; (300 to 457)	292; (234 to 366)
Anti-Polio 2 Post-booster (N = 208, 210)	8512; (7281 to 9952)	11229; (9574 to 13170)
Anti-Polio 3 Pre-booster (N = 214, 203)	257; (202 to 327)	223; (174 to 284)
Anti-Polio 3 Post-booster (N = 205, 205)	10975; (9066 to 13286)	14482; (12067 to 17380)
Anti-PT Pre-booster (N = 216, 212)	10.7; (9.37 to 12.3)	12.9; (11.3 to 14.7)
Anti-PT Post-booster (N = 226, 220)	226; (205 to 249)	325; (292 to 362)
Anti-FHA Pre-booster (N = 230, 220)	28.2; (24.5 to 32.5)	19.0; (16.7 to 21.6)
Anti-FHA Post-booster (N = 227, 221)	335; (305 to 368)	333; (305 to 363)

4. Secondary Outcome

Title	Number of Participants Reporting at Least One Solicited Injection Site or Systemic Reaction Post-booster Vaccination With PENTAXIM™
Description	Solicited Injection Site Reactions: Pain, Erythema, Swelling. Solicited Systemic Reactions: Pyrexia (Temperature), Vomiting, Crying, Somnolence, Anorexia, Irritability. Grade 3 was defined as: Pain, cries when injected limb is moved or movement of limb is reduced; Erythema and Swelling, ≥ 5 cm; Pyrexia, ≥ 39.6ºC; Vomiting, ≥ 6 episodes/24 hour or requiring parenteral hydration; Crying, > 3 hours; Somnolence, sleeping most of the time or difficulty to wake up; Anorexia, refuses ≥ 3 feeds/meals or refuses most feeds/meals; and Irritability, inconsolable.
Time Frame	Day 0 up to Day 30 post-booster vaccination

Outcome Measure Data

Analysis Population Description

Solicited injection site and systemic reactions were assessed in the enrolled and vaccinated participants, Safety Analysis Set population.

Arm/Group Title	DTacP-IPV-Hep B-PRP~T Group	PENTAXIM™ and ENGERIX B® Group
Arm/Group Description:	Participants received a booster dose of PENTAXIM™ at 18 months of age in this study. They had received 3 primary-series doses of Diphtheria (D), Tetanus (T), Pertussis (acellular component [aP]), hepatitis B (Hep B [recombinant DNA]) and poliomyelitis (Inactivated [IPV]), and Haemophilus influenzae type b (Hib) conjugated vaccine adsorbed (DTaP-IPV-HepB-PRP~T), (1 dose each at 2, 4, and 6 months of age) in Study A3L02 (NCT00831311).	Participants received a booster dose of PENTAXIM™ at 18 months of age in this study. They had received 3 primary-series doses of PENTAXIM™ and ENGERIX B® PEDIATRICO (1 dose each at 2, 4, and 6 months of age) in Study A3L02 (NCT00831311).
Overall Number of Participants Analyzed	231	223
Measure Type: Number; Unit of Measure: Participants
Injection site Pain	112	117
Grade 3 Injection site Pain	8	12
Injection site Erythema	66	93
Grade 3 Injection site Erythema	7	19
Injection site Swelling	63	89
Grade 3 Injection site Swelling	5	20
Any Pyrexia	47	44
Grade 3 Pyrexia	9	4
Any Vomiting	18	18
Grade 3 Vomiting	0	0
Any Crying	61	53
Grade 3 Crying	3	2
Any Somnolence	52	44
Grade 3 Somnolence	6	2
Any Anorexia	59	52
Grade 3 Anorexia	9	3
Any Irritability	85	78
Grade 3 Irritability	6	1

Adverse Events

Time Frame	Adverse events data were collected from Day 0 (before booster vaccination) up to Day 30 post-booster vaccination in the Safety Analysis Set population.
Adverse Event Reporting Description	The Safety Analysis Set (SafAS) was defined as the set of participants who received the booster vaccine. The analysis was based upon the number of participants for whom each safety assessment was performed.
Arm/Group Title	DTacP-IPV-Hep B-PRP~T Group		PENTAXIM™ and ENGERIX B® Group
Arm/Group Description	Participants received a booster dose of PENTAXIM™ at 18 months of age in this study. They had received 3 primary-series doses of Diphtheria (D), Tetanus (T), Pertussis (acellular component [aP]), hepatitis B (Hep B [recombinant DNA]) and poliomyelitis (Inactivated [IPV]), and Haemophilus influenzae type b (Hib) conjugated vaccine adsorbed (DTaP-IPV-HepB-PRP~T), (1 dose each at 2, 4, and 6 months of age) in Study A3L02 (NCT00831311).		Participants received a booster dose of PENTAXIM™ at 18 months of age in this study. They had received 3 primary-series doses of PENTAXIM™ and ENGERIX B® PEDIATRICO (1 dose each at 2, 4, and 6 months of age) in Study A3L02 (NCT00831311).
All-Cause Mortality
	DTacP-IPV-Hep B-PRP~T Group		PENTAXIM™ and ENGERIX B® Group
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	DTacP-IPV-Hep B-PRP~T Group		PENTAXIM™ and ENGERIX B® Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/231 (1.30%)		1/223 (0.45%)
Infections and infestations
Otitis Media Acute * 1	1/231 (0.43%)	1	0/223 (0.00%)	0
Pneumonia * 1	1/231 (0.43%)	1	0/223 (0.00%)	0
Nervous system disorders
Convulsion * 1	1/231 (0.43%)	1	0/223 (0.00%)	0
Febrile Convulsion * 1	0/231 (0.00%)	0	1/223 (0.45%)	1
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 7.1
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5.00%
	DTacP-IPV-Hep B-PRP~T Group		PENTAXIM™ and ENGERIX B® Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	134/231 (58.01%)		137/223 (61.43%)
Gastrointestinal disorders
Vomiting † 1	18/231 (7.79%)	18	18/223 (8.07%)	18
General disorders
Solicited Injection Site Erythema † 1	66/231 (28.57%)	66	93/223 (41.70%)	93
Solicited Injection Site Pain † 1	112/231 (48.48%)	112	117/223 (52.47%)	117
Solicited Injection Site Swelling † 1	63/231 (27.27%)	63	89/223 (39.91%)	89
Irritability † 1	85/231 (36.80%)	85	78/223 (34.98%)	78
Pyrexia † 1	47/231 (20.35%)	47	44/223 (19.73%)	44
Infections and infestations
Bronchitis * 1	16/231 (6.93%)	16	8/223 (3.59%)	8
Rhinitis * 1	15/231 (6.49%)	15	14/223 (6.28%)	14
Metabolism and nutrition disorders
Anorexia † 1	59/231 (25.54%)	59	52/223 (23.32%)	52
Nervous system disorders
Somnolence † 1	52/231 (22.51%)	52	44/223 (19.73%)	44
Psychiatric disorders
Crying † 1	61/231 (26.41%)	61	53/223 (23.77%)	53
† Indicates events were collected by systematic assessment; * Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 7.1

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

Publications of Results:

Tregnaghi M, Zambrano B, Santos-Lima E. Antibody persistence after a primary series of a new DTaP-IPV-Hep B-PRP-T combined vaccine or separate DTaP-IPV//PRP-T and hepatitis B vaccines at 2, 4, and 6 months of age and the effect of a subsequent DTaP-IPV//PRP-T booster vaccination at 18 months of age in healthy Argentinean infants. Pediatr Infect Dis J. 2012 Jan;31(1):e24-30. doi: 10.1097/INF.0b013e318242460a.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT00303316
• Other Study ID Numbers: A3L16
• First Submitted: March 13, 2006
• First Posted: March 16, 2006
• Results First Submitted: December 11, 2012
• Results First Posted: February 22, 2013
• Last Update Posted: February 22, 2013