Immunogenicity of Adacel® and BOOSTRIX® Vaccines in Adolescents

• ClinicalTrials.gov Identifier: NCT01629589
• Recruitment Status: Completed
• First Posted: June 27, 2012
• Results First Posted: October 21, 2013
• Last Update Posted: March 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: Tetanus; Diphtheria; Pertussis; Whooping Cough
• Interventions: Biological: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Adacel®); Biological: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine, Adsorbed (BOOSTRIX®)
• Enrollment: 423

Participant Flow

Recruitment Details	The study participants were enrolled from 20 June 2012 to 10 September 2012 at 8 centers in the United States.
Pre-assignment Details	A total of 423 participants that met all of the inclusion and none of the exclusion criteria were randomized, 422 were vaccinated in this study.

Arm/Group Title	Adacel® Vaccine Group	BOOSTRIX® Vaccine Group
Arm/Group Description	Participants received a single dose of Adacel® vaccine	Participants received a single dose of BOOSTRIX® vaccine
Period Title: Overall Study
Started	212	211
Completed	204 [1]	204
Not Completed	8	7
Reason Not Completed
Protocol Violation	4	2
Lost to Follow-up	2	1
Withdrawal by Subject	2	3
Did not receive study vaccine	0	1
[1] A participant received the Boostrix vaccine. Study data reported for the Boostrix vaccine group.

Baseline Characteristics

Arm/Group Title		Adacel® Vaccine Group	BOOSTRIX® Vaccine Group	Total
Arm/Group Description		Participants received a single dose of Adacel® vaccine	Participants received a single dose of BOOSTRIX® vaccine	Total of all reporting groups
Overall Number of Baseline Participants		212	211	423
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	212 participants	211 participants	423 participants
	<=18 years	212 100.0%	211 100.0%	423 100.0%
	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: Years
	Number Analyzed	212 participants	211 participants	423 participants
		11.6 (0.5)	11.6 (0.5)	11.6 (0.5)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	212 participants	211 participants	423 participants
	Female	105 49.5%	106 50.2%	211 49.9%
	Male	107 50.5%	105 49.8%	212 50.1%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	212 participants	211 participants	423 participants
		212	211	423

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Antibody Responses to Tetanus and Diphtheria Components Following Vaccination With Either Adacel® or BOOSTRIX® Vaccine
Description	Tetanus antibody was assayed by Enzyme-linked immunosorbent assay (ELISA) and Diphtheria antibody by a toxin neutralization test. Antibody responses to tetanus and diphtheria components were defined as titers ≥0.1 IU/mL and ≥1.0 IU/mL
Time Frame	Day 0 (pre-vaccination) to Day 28 (post-vaccination)

Outcome Measure Data

Analysis Population Description

The antibody responses to tetanus and diphtheria components were determined in the Per-Protocol Analysis Set.

Arm/Group Title	Adacel® Vaccine Group	BOOSTRIX® Vaccine Group
Arm/Group Description:	Participants received a single dose of Adacel® vaccine	Participants received a single dose of BOOSTRIX® vaccine
Overall Number of Participants Analyzed	196	194
Measure Type: Number; Unit of Measure: Participants
Tetanus (pre-vaccination) ≥0.1 IU/mL	172	177
Tetanus (post-vaccination) ≥0.1 IU/mL	196	194
Diphtheria (pre-vaccination) ≥0.1 IU/mL	135	139
Diphtheria (post-vaccination) ≥ 0.1 IU/mL	196	194
Tetanus (pre-vaccination) ≥ 1.0 IU/mL	33	48
Tetanus (post-vaccination) ≥ 1.0 IU/mL	195	194
Diphtheria (pre-vaccination) ≥1.0 IU/mL	28	26
Diphtheria (post-vaccination) ≥1.0 IU/mL	183	186

2. Secondary Outcome

Title	Geometric Mean Concentrations of Tetanus and Diphtheria Antibodies Following Vaccination With Either Adacel® or BOOSTRIX® Vaccine
Description	Tetanus antibody was assayed by Enzyme-linked immunosorbent assay (ELISA) and Diphtheria antibody by a toxin neutralization test
Time Frame	Day 0 (pre-vaccination) to Day 28 post-vaccination

Outcome Measure Data

Analysis Population Description

The geometric mean concentrations of tetanus and diphtheria antibodies were determined in the Per Protocol Analysis Set.

Arm/Group Title	Adacel® Vaccine Group	BOOSTRIX® Vaccine Group
Arm/Group Description:	Participants received a single dose of Adacel® vaccine	Participants received a single dose of BOOSTRIX® vaccine
Overall Number of Participants Analyzed	196	194
Geometric Mean (95% Confidence Interval); Unit of Measure: Titers
Tetanus (pre-vaccination)	0.422; (0.363 to 0.492)	0.456; (0.393 to 0.528)
Tetanus (post-vaccination)	18.9; (16.4 to 21.8)	9.18; (8.10 to 10.4)
Diphtheria (pre-vaccination)	0.211; (0.171 to 0.260)	0.221; (0.181 to 0.269)
Diphtheria (post-vaccination)	8.17; (6.83 to 9.77)	5.62; (4.85 to 6.51)

3. Secondary Outcome

Title	Number of Participants With Booster Responses Against Tetanus and Diphtheria Antigens Following Vaccination With Either Adacel® or BOOSTRIX® Vaccine
Description	Adacel booster response defined as: a 4-fold increase in pre- to post-vaccination antibody concentrations for subjects with a pre-vaccination concentration ≤2.56 IU/mL for diphtheria and ≤2.7 IU/mL for tetanus, and defined as a 2-fold increase for subjects with a pre-vaccination concentration >2.56 IU/mL for diphtheria and >2.7 IU/mL for tetanus. Boostrix booster response defined as: a post-vaccination titer ≥4 times the lower limit of quantitation (LLOQ) for subjects with a pre-vaccination titer < LLOQ, a post-vaccination titer ≥4 times the pre-vaccination titer for subjects with a pre-vaccination titer between LLOQ and 4x LLOQ, or a post-vaccination titer at least twice the pre-vaccination titer for subjects with a pre-vaccination titer ≥4x LLOQ.
Time Frame	Day 28 post-vaccination

Outcome Measure Data

Analysis Population Description

Booster response against tetanus and diphtheria components were determined in the Per-Protocol Analysis Set.

Arm/Group Title	Adacel® Vaccine Group	BOOSTRIX® Vaccine Group
Arm/Group Description:	Participants received a single dose of Adacel® vaccine	Participants received a single dose of BOOSTRIX® vaccine
Overall Number of Participants Analyzed	196	194
Measure Type: Number; Unit of Measure: Participants
Tetanus	194	191
Diphtheria	189	188

4. Secondary Outcome

Title	Geometric Mean Concentrations of the Pertussis Antibodies Following Vaccination With Either Adacel® or BOOSTRIX® Vaccine
Description	Pertussis antibodies Pertussis toxoid (PT), Filamentous hemagglutinin (FHA), Pertactin (PRN), and Fimbriae types 2 and 3 (FIM 2&3) were assayed by Enzyme-linked immunosorbent assay (ELISA)
Time Frame	Day 0 (pre-vaccination) to Day 28 post-vaccination

Outcome Measure Data

Analysis Population Description

Geometric mean concentrations of the Pertussis antibodies were determined in the Per-Protocol Analysis Set.

Arm/Group Title	Adacel® Vaccine Group	BOOSTRIX® Vaccine Group
Arm/Group Description:	Participants received a single dose of Adacel® vaccine	Participants received a single dose of BOOSTRIX® vaccine
Overall Number of Participants Analyzed	196	194
Geometric Mean (95% Confidence Interval); Unit of Measure: Titers
Pertussis toxoid (pre-vaccination)	5.59; (4.67 to 6.68)	5.69; (4.71 to 6.88)
Pertussis toxoid (post-vaccination)	31.0; (27.0 to 35.7)	44.1; (39.0 to 49.9)
Filamentous hemagglutinin (pre-vaccination)	22.7; (19.0 to 27.2)	22.7; (19.4 to 26.6)
Filamentous hemagglutinin (post-vaccination)	255; (228 to 286)	318; (292 to 347)
Pertactin (pre-vaccination)	12.3; (10.5 to 14.4)	10.3; (8.99 to 11.9)
Pertactin (post-vaccination)	263; (223 to 310)	252; (214 to 295)
Fimbriae types 2 and 3 (pre-vaccination)	5.95; (4.88 to 7.24)	6.55; (5.33 to 8.04)
Fimbriae types 2 and 3 (post-vaccination)	346; (269 to 446)	11.1; (8.79 to 14.0)

5. Secondary Outcome

Title	Number of Participants With Booster Responses Against the Pertussis Antibodies Following Vaccination With Either Adacel® or BOOSTRIX® Vaccine
Description	Adacel booster response defined as: a 4-fold increase in pre- to post-vaccination antibody concentrations for subjects with a pre vaccination concentration ≤93 ELISA Unit (EU)/mL for Pertussis toxoid (PT), ≤170 EU/mL for Filamentous hemagglutinin (FHA), ≤115 EU mL for pertactin (PRN), or ≤285 EU/mL for Fimbriae types 2 and 3 (FIM), and defined as a 2-fold increase for subjects with a pre-vaccination concentration >93 EU/mL for PT, >170 EU/mL for FHA, >115 EU/mL for PRN, or >285 EU/mL for FIM. Boostrix booster response defined as: a post-vaccination titer ≥4 times the LLOQ for subjects with a pre-vaccination titer <LLOQ, a post-vaccination titer ≥4 times the pre-vaccination titer for subjects with a pre-vaccination titer between LLOQ and 4x LLOQ, or a post-vaccination titer at least twice the pre-vaccination titer for subjects with a pre-vaccination titer ≥4x LLOQ.
Time Frame	Day 28 post-vaccination

Outcome Measure Data

Analysis Population Description

Booster response against Pertussis antibodies were determined in the Per-Protocol Analysis Set.

Arm/Group Title	Adacel® Vaccine Group	BOOSTRIX® Vaccine Group
Arm/Group Description:	Participants received a single dose of Adacel® vaccine	Participants received a single dose of BOOSTRIX® vaccine
Overall Number of Participants Analyzed	196	194
Measure Type: Number; Unit of Measure: Participants
Pertussis toxoid	97	142
Filamentous hemagglutinin	167	189
Pertactin	186	189
Fimbriae types 2 and 3	181	31

6. Secondary Outcome

Title	Number of Participants Reporting Immediate Unsolicited Adverse Events Following Vaccination With Either Adacel® or BOOSTRIX® Vaccine
Description	The occurrence, nature (Medical Dictionary for Regulatory Activities (MedDRA) preferred term), duration, intensity, and relationship to vaccination of adverse events (AEs) reported in the 15 minutes after vaccination and systemic AEs.
Time Frame	Up to 15 minutes post-vaccination

Outcome Measure Data

Analysis Population Description

Number of participants reporting immediate unsolicited adverse events was determined in all participants in the Safety Analysis Set.

Arm/Group Title	Adacel® Vaccine Group	BOOSTRIX® Vaccine Group
Arm/Group Description:	Participants received a single dose of Adacel® vaccine	Participants received a single dose of BOOSTRIX® vaccine
Overall Number of Participants Analyzed	211	211
Measure Type: Number; Unit of Measure: Participants
Headache	1	0
Nausea	1	0

Adverse Events

Time Frame	Adverse event data were collected from Day 0 up to Day 28 post-vaccination.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Adacel® Vaccine Group		BOOSTRIX® Vaccine Group
Arm/Group Description	Participants received a single dose of Adacel® vaccine		Participants received a single dose of BOOSTRIX® vaccine
All-Cause Mortality
	Adacel® Vaccine Group		BOOSTRIX® Vaccine Group
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	Adacel® Vaccine Group		BOOSTRIX® Vaccine Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/211 (0.00%)		0/211 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5.00%
	Adacel® Vaccine Group		BOOSTRIX® Vaccine Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	58/211 (27.49%)		70/211 (33.18%)
General disorders
Injection Site Pain † 1	34/211 (16.11%)	36	43/211 (20.38%)	46
Nervous system disorders
Headache † 1	21/211 (9.95%)	26	31/211 (14.69%)	39
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain † 1	11/211 (5.21%)	11	4/211 (1.90%)	5
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA 14.0

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Decker MD, Greenberg DP, Johnson DR, Pool V. Randomized study of immune responses to two Tdap vaccines among adolescents primed with DTaP and comparison with results among adolescents primed with DTwP. Vaccine. 2019 Aug 14;37(35):5003-5008. doi: 10.1016/j.vaccine.2019.07.015. Epub 2019 Jul 10.

• Responsible Party: Sanofi ( Sanofi Pasteur, a Sanofi Company )
• ClinicalTrials.gov Identifier: NCT01629589
• Other Study ID Numbers: Td551; U1111-1127-6774 ( Other Identifier: WHO )
• First Submitted: June 22, 2012
• First Posted: June 27, 2012
• Results First Submitted: August 16, 2013
• Results First Posted: October 21, 2013
• Last Update Posted: March 2, 2016