Immunogenicity Study of Antibody Persistence and Booster Effect of DTaP-HB PRP~T Combined Vaccine in Filipino Infants

• ClinicalTrials.gov Identifier: NCT00514709
• Recruitment Status: Completed
• First Posted: August 10, 2007
• Results First Posted: November 14, 2013
• Last Update Posted: August 2, 2016
• Sponsor: Sanofi Pasteur, a Sanofi Company
• Information provided by (Responsible Party): Sanofi ( Sanofi Pasteur, a Sanofi Company )

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
• Conditions: Diphtheria; Tetanus; Pertussis; Hepatitis B; Influenza
• Interventions: Biological: DTaP-HB PRP~T Combined Vaccine; Biological: DTaP-HB-PRP~T vaccine; Biological: Oral Polio Vaccine
• Enrollment: 1843

Participant Flow

Recruitment Details	Participants were randomized and enrolled from 06 August 2007 to 29 July 2008 in 2 clinic centers in the Philippines.
Pre-assignment Details	A total of 1843 participants who met all the inclusion and none of the exclusion criteria were enrolled and vaccinated.

Arm/Group Title	Group 1: DTaP-Hep B-PRP~T + OPV	Group 2: Tritanrix-Hep B/ Hib™ + OPV
Arm/Group Description	Participants received a booster dose of the DTaP-Hep B-PRP~T Combined vaccine concomitantly with oral polio vaccine (OPV) following a 3-dose primary series of DTaP-Hep B-PRP~T combined vaccine concomitantly with OPV at 6, 10, and 14 weeks of age in Study AL201 (NCT00348881).	Participants received a booster dose of the DTaP-Hep B-PRP~T Combined vaccine concomitantly with oral polio vaccine (OPV) following a 3-dose primary series of Tritanrix-Hep B/Hib™ concomitantly with OPV at 6, 10, and 14 weeks of age in Study AL201 (NCT00348881).
Period Title: Overall Study
Started	1230	613
Completed	1230	613
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Group 1: DTaP-Hep B-PRP~T + OPV	Group 2: Tritanrix-Hep B/ Hib™ + OPV	Total
Arm/Group Description		Participants received a booster dose of the DTaP-Hep B-PRP~T Combined vaccine concomitantly with oral polio vaccine (OPV) following a 3-dose primary series of DTaP-Hep B-PRP~T combined vaccine concomitantly with OPV at 6, 10, and 14 weeks of age in Study AL201.	Participants received a booster dose of the DTaP-Hep B-PRP~T Combined vaccine concomitantly with oral polio vaccine (OPV) following a 3-dose primary series of Tritanrix-Hep B/Hib™ concomitantly with OPV at 6, 10, and 14 weeks of age in Study AL201.	Total of all reporting groups
Overall Number of Baseline Participants		1230	613	1843
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1230 participants	613 participants	1843 participants
	<=18 years	1230 100.0%	613 100.0%	1843 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	1230 participants	613 participants	1843 participants
		15.1 (1.96)	15.1 (1.95)	15.1 (1.96)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1230 participants	613 participants	1843 participants
	Female	629 51.1%	302 49.3%	931 50.5%
	Male	601 48.9%	311 50.7%	912 49.5%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Philippines	Number Analyzed	1230 participants	613 participants	1843 participants
		1230	613	1843

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Antibody Persistence and Immunogenicity Booster Response to Vaccination With DTaP-Hep B-PRP~T Concomitantly With Oral Polio Vaccine (OPV)
Description	Immunogenicity was assessed by means of radioimmunoassay (RIA) for anti-Hepatitis B (Hep Bs) and anti-PRP antibodies, enzyme immunoassay (EIA) for anti-Tetanus, and serum neutralization (SN) for anti-Diphtheria. Booster responses defined as titers ≥ 10 mIU/mL for anti-Hep Bs; ≥ 0.15 μg/mL for anti-PRP; ≥ 0.01 IU/mL for anti-Tetanus and anti-Diphtheria; Pertussis Toxoid and Filamentous Hemagglutinin (FHA) 4-fold increase and booster response.
Time Frame	Day 0 (pre-vaccination) and Day 28 post-booster vaccination

Outcome Measure Data

Analysis Population Description

Antibody persistence and immunogenicity booster responses were assessed in a subset of participants available for the endpoint, the per-protocol population.

Arm/Group Title	Group 1: DTaP-Hep B-PRP~T + OPV	Group 2: Tritanrix-Hep B/ Hib™ + OPV
Arm/Group Description:	Participants received a booster dose of the DTaP-Hep B-PRP~T Combined vaccine concomitantly with oral polio vaccine (OPV) following a 3-dose primary series of DTaP-Hep B-PRP~T combined vaccine concomitantly with OPV at 6, 10, and 14 weeks of age in Study AL201.	Participants received a booster dose of the DTaP-Hep B-PRP~T Combined vaccine concomitantly with oral polio vaccine (OPV) following a 3-dose primary series of Tritanrix-Hep B/Hib™ concomitantly with OPV at 6, 10, and 14 weeks of age in Study AL201.
Overall Number of Participants Analyzed	93	105
Measure Type: Number; Unit of Measure: Participants
Anti-Hep B Pre-booster (N = 93, 103)	81	80
Anti-Hep B Post-booster (N = 93, 105)	91	103
Anti-PRP Pre-booster (N = 93, 105)	78	105
Anti-PRP Post-booster (N = 93, 105)	93	105
Anti-Diphtheria Pre-booster (N = 93, 105)	72	68
Anti-Diphtheria Post-booster (N = 93, 105)	93	103
Anti-Tetanus Pre-booster (N = 93, 105)	93	105
Anti-Tetanus Post-booster (N = 93, 105)	93	105
Anti-Pertussis 4-Fold increase (N = 89, 101)	85	100
Anti-Pertussis booster response (N = 89, 101)	87	101
Anti-FHA 4-Fold increase (N = 91, 103)	80	102
Anti-FHA booster response (N = 91, 103)	89	102

2. Secondary Outcome

Title	Geometric Mean Titers (GMTs) of Vaccine Antibodies After Booster Vaccination With DTaP-Hep B-PRP~T Combined Vaccine Concomitantly With Oral Polio Vaccine (OPV)
Description	Immunogenicity was assessed by means of radioimmunoassay (RIA) for anti-Hepatitis B (Hep Bs) and anti-PRP antibodies, enzyme immunoassay (EIA) for anti-Tetanus, and serum neutralization (SN) for anti-Diphtheria following the booster vaccination.
Time Frame	Day 0 (pre-vaccination) and Day 28 post-vaccination

Outcome Measure Data

Analysis Population Description

GMTs were assessed in a sub-set of the participants available for the endpoint, the per-protocol population.

Arm/Group Title	Group 1: DTaP-Hep B-PRP-T + OPV	Group 2: Tritanrix-Hep B/ Hib™ + OPV
Arm/Group Description:	Participants received a booster dose of the DTaP-Hep B-PRP~T Combined vaccine following a 3-dose primary series of DTaP-Hep B-PRP-T combined vaccine concomitantly with OPV at 6, 10, and 14 weeks of age in Study AL201.	Participants received a booster dose of the DTaP-Hep B-PRP~T Combined vaccine following a 3-dose primary series of Tritanrix-Hep B/ Hib™ concomitantly with OPV at 6, 10, and 14 weeks of age in Study AL201.
Overall Number of Participants Analyzed	93	105
Geometric Mean (95% Confidence Interval); Unit of Measure: Titers
Anti-Hep B Pre-booster (N = 93, 103)	71.6; (51.1 to 100)	42.2; (30.5 to 58.5)
Anti-Hep Bs Post-booster (N = 93, 105)	4224; (2760 to 6464)	3673; (2441 to 5527)
Anti-PRP Pre-booster (N = 93, 105)	0.889; (0.602 to 1.31)	5.32; (4.13 to 6.84)
Anti-PRP Post-booster (N = 93, 105)	58.1; (40.4 to 83.4)	242; (195 to 299)
Anti-Diphtheria Pre-booster (N = 93, 105)	0.016; (0.013 to 0.021)	0.014; (0.011 to 0.018)
Anti-Diphtheria Post-booster (N = 93, 105)	1.36; (1.05 to 1.77)	1.43; (1.06 to 1.93)
Anti-Tetanus pre-booster (N = 93, 105)	0.364; (0.308 to 0.431)	0.504; (0.438 to 0.581)
Anti-Tetanus post-booster (N = 93, 105)	11.6; (9.71 to 13.9)	24.7; (21.9 to 27.7)
Anti-Pertusiss pre-booster (N = 89, 101)	7.34; (6.22 to 8.64)	6.82; (5.30 to 8.76)
Anti-Pertusiss post-booster (N = 93, 105)	128; (107 to 153)	185; (149 to 229)
Anti-FHA Pre-booster (N = 91,103)	14.0; (11.3 to 17.3)	2.21; (1.83 to 2.67)
Anti-FHA Post-booster (N = 91,103)	204; (179 to 233)	158; (135 to 185)

3. Secondary Outcome

Title	Number of Participants Reporting Solicited Injection Site Reaction or Systemic Reactions Following Vaccination With a Booster Dose of the DTaP-Hep B-PRP~T Combined Vaccine Concomitantly With Oral Polio Vaccine (OPV)
Description	Solicited injection site reactions: Pain, Erythema, and Swelling; Solicited systemic reactions; Pyrexia (temperature), Vomiting, Abnormal Crying, Drowsiness, Loss of Appetite, and irritability. Grade 3 reactions are defined as: Pain - cries when injected limb is moved; Erythema and Swelling - ≥ 5cm; Fever - rectal temperature ≥ 39.5ºC; Vomiting - ≥6 episodes per 24 hours; Crying - inconsolable crying for >3 hours; Somnolence - sleeping most of the time or difficulty to wake up; Anorexia - refuses ≥3 feeds; and Irritability - inconsolable.
Time Frame	Day 0 up to Day 7 after vaccination

Outcome Measure Data

Analysis Population Description

Safety was assessed on the safety analysis (intent-to-treat) population.

Arm/Group Title	Group 1: DTaP-Hep B-PRP~T + OPV	Group 2: Tritanrix-Hep B/ Hib™ + OPV
Arm/Group Description:	Participants received a booster dose of the DTaP-Hep B-PRP~T Combined vaccine concomitantly with oral polio vaccine (OPV) following a 3-dose primary series of DTaP-Hep B-PRP~T combined vaccine concomitantly with OPV at 6, 10, and 14 weeks of age in Study AL201.	Participants received a booster dose of the DTaP-Hep B-PRP~T Combined vaccine concomitantly with oral polio vaccine (OPV) following a 3-dose primary series of Tritanrix-Hep B/Hib™ concomitantly with OPV at 6, 10, and 14 weeks of age in Study AL201.
Overall Number of Participants Analyzed	1230	613
Measure Type: Number; Unit of Measure: Participants
Injection site Pain post-vaccination	411	216
Grade 3 Injection site Pain post-vaccination	10	1
Injection site Erythema post-vaccination	272	136
Grade 3 Injection site Erythema post-vaccination	7	3
Injection site Swelling post-vaccination	211	120
Grade 3 Injection site Swelling post-vaccination	7	4
Extensive swelling of vaccinated limb	0	0
Pyrexia post-vaccination	137	70
Grade 3 Pyrexia post-vaccination	0	3
Vomiting post-vaccination	53	33
Grade 3 Vomiting post-vaccination	3	0
Crying post-vaccination	98	58
Grade 3 Crying post-vaccination	0	0
Somnolence post-vaccination	114	73
Grade 3 Somnolence post-vaccination	0	0
Anorexia post-vaccination	97	53
Grade 3 Anorexia post-vaccination	2	3
Irritability post-vaccination	224	114
Grade 3 Irritability post-vaccination	1	0

Adverse Events

Time Frame	Adverse event data were collected from Day 0 (post-vaccination) up to Day 30 post-vaccination.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Group 1: DTaP-Hep B-PRP~T + OPV		Group 2: Tritanrix-Hep B/ Hib™ + OPV
Arm/Group Description	Participants received a booster dose of the DTaP-Hep B-PRP~T Combined vaccine concomitantly with oral polio vaccine (OPV) following a 3-dose primary series of DTaP-Hep B-PRP~T combined vaccine concomitantly with OPV at 6, 10, and 14 weeks of age in Study AL201.		Participants received a booster dose of the DTaP-Hep B-PRP~T Combined vaccine concomitantly with oral polio vaccine (OPV) following a 3-dose primary series of Tritanrix-Hep B/Hib™ concomitantly with OPV at 6, 10, and 14 weeks of age in Study AL201.
All-Cause Mortality
	Group 1: DTaP-Hep B-PRP~T + OPV		Group 2: Tritanrix-Hep B/ Hib™ + OPV
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Group 1: DTaP-Hep B-PRP~T + OPV		Group 2: Tritanrix-Hep B/ Hib™ + OPV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/1230 (0.24%)		0/613 (0.00%)
Infections and infestations
Gastroenteritis * 1	2/1230 (0.16%)	2	0/613 (0.00%)	0
Meningitis tuberculous * 1	1/1230 (0.08%)	1	0/613 (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%
	Group 1: DTaP-Hep B-PRP~T + OPV		Group 2: Tritanrix-Hep B/ Hib™ + OPV
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	411/1230 (33.41%)		216/613 (35.24%)
Gastrointestinal disorders
Vomiting * 1	53/1230 (4.31%)		33/613 (5.38%)
General disorders
Solicited injection site Pain † 1	411/1230 (33.41%)		216/613 (35.24%)
Solicited injection site Erythema † 1	272/1230 (22.11%)		136/613 (22.19%)
Solicited injection site Swelling † 1	211/1230 (17.15%)		120/613 (19.58%)
Pyrexia † 1	137/1230 (11.14%)		70/613 (11.42%)
Infections and infestations
Upper respiratory tract infection * 1	69/1230 (5.61%)		38/613 (6.20%)
Metabolism and nutrition disorders
Anorexia † 1	97/1230 (7.89%)		53/613 (8.65%)
Nervous system disorders
Somnolence † 1	114/1230 (9.27%)		73/613 (11.91%)
Psychiatric disorders
Crying † 1	98/1230 (7.97%)		58/613 (9.46%)
Irritability † 1	224/1230 (18.21%)		114/613 (18.60%)
† Indicates events were collected by systematic assessment; * Indicates events were collected by non-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: NCT00514709
• Other Study ID Numbers: AL204
• First Submitted: August 9, 2007
• First Posted: August 10, 2007
• Results First Submitted: September 9, 2013
• Results First Posted: November 14, 2013
• Last Update Posted: August 2, 2016