Descriptive, Open-label, Multicenter Study of the Safety of Redosing With ADACEL® Vaccine - Study Results

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized; Endpoint Classification: Safety Study; Intervention Model: Single Group Assignment; Masking: Open Label; Primary Purpose: Prevention
Conditions:	Tetanus Diphtheria Pertussis
Intervention:	Biological: Tetanus-diphtheria-acellular pertussis (Tdap) vaccine

Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were enrolled from 21 August 2006, to 12 April 2007, in 6 clinical centers in the US and 6 clinical centers in Canada.

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
A total of 545 participants were enrolled and vaccinated in the study. Data on 544 participants that met the inclusion and exclusion criteria were analyzed and reported. One participant who did not receive Adacel® vaccine in one of the previous studies was excluded from the Safety Analysis Set.

Reporting Groups

	Description
Adacel® Vaccine Group	Participants 15 to 69 years of age who received a dose of Adacel vaccine in one of three previous studies (Td501, or Td502, or Td505), revaccinated in Study Td518.

Participant Flow: Overall Study

	Adacel® Vaccine Group
STARTED	544
COMPLETED	540
NOT COMPLETED	4
Adverse Event	1
Protocol Violation	2
Withdrawal by Subject	1

Baseline Characteristics

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Reporting Groups

	Description
Adacel® Vaccine Group	Participants 15 to 69 years of age who received a dose of Adacel vaccine in one of three previous studies (Td501, or Td502, or Td505), revaccinated in Study Td518.

Baseline Measures

	Adacel® Vaccine Group
Number of Participants [units: participants]	544
Age [units: participants]
<=18 years	169
Between 18 and 65 years	368
>=65 years	7
Age [units: Years] Mean ± Standard Deviation	31.7 ± 15.7
Gender [units: participants]
Female	284
Male	260
Region of Enrollment [units: participants]
United States	194
Canada	350

Outcome Measures

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1. Primary:

Percentage of Participants With at Least 1 Solicited Injection Site and Systemic Reactions Post-Vaccination [ Time Frame: 0-14 days post-vaccination ]

Measure Type	Primary
Measure Title	Percentage of Participants With at Least 1 Solicited Injection Site and Systemic Reactions Post-Vaccination
Measure Description	Solicited Injection Site Reactions: Pain, Erythema/Redness, Swelling. Solicited Systemic Reactions: Fever (Temperature), Headache, Myalgia, Malaise.
Time Frame	0-14 days post-vaccination
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety analysis was on all enrolled and vaccinated participants with available reaction data, intent-to-treat population. The solicited systemic reaction, malaise was not collected in the previous studies.

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Safety analysis was on all enrolled and vaccinated participants with available reaction data, intent-to-treat population.

The solicited systemic reaction, malaise was not collected in the previous studies.

Reporting Groups

	Description
Adacel® Vaccine Group	Participants 15 to 69 years of age who received a dose of Adacel vaccine in one of three previous studies (Td501, or Td502, or Td505), revaccinated in Study Td518.

Measured Values

	Adacel® Vaccine Group
Number of Participants Analyzed [units: participants]	544
Percentage of Participants With at Least 1 Solicited Injection Site and Systemic Reactions Post-Vaccination [units: Percentage of Participants]
Any Solicited Injection Site Reaction	89
Any Injection Site Pain	88
Grade 3 Injection Site Pain (Incapacitating)	2
Any Injection Site Erythema/Redness	29
Grade 3 Injection Site Erythema/Redness (≥ 5 cm)	3
Any Injection Site Swelling	26
Grade 3 Injection Site Swelling (≥ 5 cm)	3
Any Fever	7
Grade 3 Fever (> 39.0 ºC or > 102.2 ºF)	1
Any Headache	53
Grade 3 Headache (Prevents daily activities)	3
Any Myalgia	61
Grade 3 Myalgia (Prevents daily activities)	4
Any Malaise	38
Grade 3 Malaise (Prevents daily activities)	3

No statistical analysis provided for Percentage of Participants With at Least 1 Solicited Injection Site and Systemic Reactions Post-Vaccination

2. Other Pre-specified:

Geometric Mean Titers (GMTs) of Tetanus and Diphtheria Antibodies Pre- and Post-Vaccination. [ Time Frame: Day 28 post-vaccination ]

Measure Type	Other Pre-specified
Measure Title	Geometric Mean Titers (GMTs) of Tetanus and Diphtheria Antibodies Pre- and Post-Vaccination.
Measure Description	Pre- and post-vaccination GMTs and their 95% confidence intervals for diphtheria were determined by toxin neutralization testing; the other antibody levels were determined by enzymed-linked immunosorbent assay testing.
Time Frame	Day 28 post-vaccination
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Geometric mean titers were assessed in the per-protocol population.

Reporting Groups

	Description
Adacel® Vaccine Group	Participants 15 to 69 years of age who received a dose of Adacel vaccine in one of three previous studies (Td501, or Td502, or Td505), revaccinated in Study Td518.

Measured Values

	Adacel® Vaccine Group
Number of Participants Analyzed [units: participants]	451
Geometric Mean Titers (GMTs) of Tetanus and Diphtheria Antibodies Pre- and Post-Vaccination. [units: IU/mL] Geometric Mean ( 95% Confidence Interval )
Tetanus (IU/mL) Pre-Dose, n = 445	1.41 ( 1.27 to 1.56 )
Tetanus (IU/mL) Post-Dose, n = 445	9.62 ( 9.06 to 10.2 )
Diphtheria (IU/mL) no Menactra Pre-Dose, n = 379	0.133 ( 0.110 to 0.162 )
Diphtheria (IU/mL) no Menactra Post-Dose n = 379	2.17 ( 1.84 to 2.56 )
Diphtheria (IU/mL) with Menactra Pre-Dose n = 64	4.45 ( 2.77 to 7.15 )
Diphtheria (IU/mL) with Menactra Post-Dose n = 64	8.70 ( 6.59 to 11.5 )

No statistical analysis provided for Geometric Mean Titers (GMTs) of Tetanus and Diphtheria Antibodies Pre- and Post-Vaccination.

3. Other Pre-specified:

Geometric Mean Titers (GMTs) of Pertussis Antibodies Pre- and Post-Vaccination. [ Time Frame: Day 28 post-vaccination ]

Measure Type	Other Pre-specified
Measure Title	Geometric Mean Titers (GMTs) of Pertussis Antibodies Pre- and Post-Vaccination.
Measure Description	Pre- and post-vaccination GMTs and their 95% confidence intervals for Pertussis were determined by enzymed-linked immunosorbent assay testing.
Time Frame	Day 28 post-vaccination
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Geometric mean titers were assessed in the per-protocol population.

Reporting Groups

	Description
Adacel® Vaccine Group	Participants 15 to 69 years of age who received a dose of Adacel vaccine in one of three previous studies (Td501, or Td502, or Td505), revaccinated in Study Td518.

Measured Values

	Adacel® Vaccine Group
Number of Participants Analyzed [units: participants]	451
Geometric Mean Titers (GMTs) of Pertussis Antibodies Pre- and Post-Vaccination. [units: EU/mL] Geometric Mean ( 95% Confidence Interval )
Pertussis PT (EU/mL) Pre-Dose, n = 381	21.3 ( 19.4 to 23.5 )
Pertussis PT (EU/mL) Post-Dose, n = 425	104 ( 97.0 to 112 )
Pertussis FHA (EU/mL) Pre-Dose, n = 450	34.6 ( 31.9 to 37.5 )
Pertussis FHA (EU/mL) Post-Dose, n = 450	201 ( 189 to 215 )
Pertussis PRN (EU/mL) Pre-Dose, n = 451	37.3 ( 32.7 to 42.6 )
Pertussis PRN (EU/mL) Post-Dose, n = 451	218 ( 201 to 236 )
Pertussis FIM (EU/mL) Pre-Dose, n = 445	165 ( 145 to 187 )
Pertussis FIM (EU/mL) Post-Dose, n = 450	749 ( 697 to 806 )

No statistical analysis provided for Geometric Mean Titers (GMTs) of Pertussis Antibodies Pre- and Post-Vaccination.

4. Other Pre-specified:

Percentage of Participants With Tetanus and Diptheria Antibody Titers ≥ 0.1 Pre- and Post-Vaccination With Adacel® [ Time Frame: Day 28 post-vaccination ]

Measure Type	Other Pre-specified
Measure Title	Percentage of Participants With Tetanus and Diptheria Antibody Titers ≥ 0.1 Pre- and Post-Vaccination With Adacel®
Measure Description	Seroprotection: Tetanus or diphtheria titer ≥ 0.1 after Adacel® vaccination. Tetanus titers determined by enzyme-linked immunosorbent assay; diphtheria titers determined by toxin neutralization assay.
Time Frame	Day 28 post-vaccination
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Tetanus and diphtheria antibody analyses were in all enrolled and vaccinated participants in the per-protocol population. Diphtheria antibody titers were analyzed separately for participants without and with an intervening Menactra vaccination between the previous study and Study Td518.

Reporting Groups

	Description
Adacel® Vaccine Group	Participants 15 to 69 years of age who received a dose of Adacel vaccine in one of three previous studies (Td501, or Td502, or Td505), revaccinated in Study Td518.

Measured Values

	Adacel® Vaccine Group
Number of Participants Analyzed [units: participants]	451
Percentage of Participants With Tetanus and Diptheria Antibody Titers ≥ 0.1 Pre- and Post-Vaccination With Adacel® [units: Percentage of Participants]
Tetanus (IU/mL) Pre-Dose	96
Tetanus (IU/mL) Post-Dose	100
Diphtheria (IU/mL) without Menactra, Pre-Dose	61
Diphtheria (IU/mL) without Menactra, Post-Dose	95
Diphtheria (IU/mL) Menactra, Pre-Dose	95
Diphtheria (IU/mL) Menactra, Post-Dose	100

No statistical analysis provided for Percentage of Participants With Tetanus and Diptheria Antibody Titers ≥ 0.1 Pre- and Post-Vaccination With Adacel®

Serious Adverse Events

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Other Adverse Events

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More Information

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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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: 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

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Medical Director
Organization: Sanofi Pasteur Inc.
e-mail: RegistryContactUs@sanofipasteur.com

No publications provided

Responsible Party:	Medical Director, Sanofi Pasteur Inc
ClinicalTrials.gov Identifier:	NCT00347958 History of Changes
Other Study ID Numbers:	TD518
Study First Received:	July 3, 2006
Results First Received:	May 14, 2010
Last Updated:	June 22, 2010
Health Authority:	United States: Food and Drug Administration Canada: Health Canada