Safety and Immunogenicity of DAPTACEL® as 5th Dose in Children 4 to 6 Years Old After 4 Doses of Pentacel™ or DAPTACEL®

• Sponsor: Sanofi Pasteur, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00258895
• Collaborator: (none)
• Enrollment: 649
• Locations: 22
• Arms: 2
• Duration (Months): 25
• Patients Per Site: 29.5
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

Primary Objectives:

1. To present the safety profile after a 5th dose of DAPTACEL® in children 4 to 6 years of age who have previously received 4 doses of DAPTACEL® or Pentacel™.

2. To present the pre-Dose 5 and post-Dose 5 antibody responses to the antigens in DAPTACEL® in children 4 to 6 years of age who have previously received 4 doses of DAPTACEL® or Pentacel™.

Observational Objectives:

1. To compare under equivalence criteria the pre-Dose 5 and post-Dose 5 antibody responses to the antigens in DAPTACEL® in children 4 to 6 years of age who have previously received 4 doses of DAPTACEL® or Pentacel™.

2. To present the pre-vaccination anti-poliovirus GMTs and seroprotection rates.

3. To present the post-vaccination anti-poliovirus GMTs and seroprotection rates among subjects receiving a 4th dose of IPV concurrently with the 5th dose of DAPTACEL and a 2nd dose of MMR.

Condition or Disease	Intervention/Treatment	Phase
Diphtheria; Tetanus; Pertussis	Biological: DAPTACEL®: DTaP; Biological: DAPTACEL®: DTaP	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 649 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Safety and Immunogenicity of DAPTACEL® Administered as a 5th Dose in 4 to 6-Year-Old Children Previously Immunized With DAPTACEL® or Pentacel®
• Study Start Date: Mar 1, 2005
• Actual Primary Completion Date: Dec 1, 2006
• Actual Study Completion Date: Apr 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DAPTACEL Primed Participants received Daptacel in Study P3T06.	Biological: DAPTACEL®: DTaP; 0.5 mL, Intramuscular; Other Names: DAPTACEL®
Experimental: Pentacel Primed Participants received Pentacel in Study P3T06	Biological: DAPTACEL®: DTaP; 0.5 mL, Intramuscular; Other Names: DAPTACEL®

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Reporting Solicited Local or Systemic Reactions Post-Dose 5 of DAPTACEL® Vaccination [0 to 7 days Post-Dose 5]

2. Percentage of Participants With Anti-Pertussis 4-Fold Rises Post-Dose 5 of DAPTACEL® Vaccination [Day 28 to 48 Post-dose 5]

   Anti-Pertussis (anti-Pertussis, anti-Filamentous Haemagglutinin, anti-Fimbriae, and anti-Pertactin) Fold-rise is calculated as post-Dose 5/pre-Dose 5 titer.

3. Percentage of Participants With Anti-Pertussis Booster Response Post-Dose 5 of DAPTACEL® Vaccination [Day 28 to 48 Post-Dose 5]

   Booster response calculation: If pre-Dose 5 titer < 4x limit of quantitation (LOQ) a 4-fold rise of post-Dose 5/pre-Dose 5. If pre-Dose 5 titer ≥ 4x LOQ a 2-fold rise of post-Dose 5/pre-Dose 5.

4. Percentage of Participants With Anti-Diphtheria and Anti-Tetanus Toxoids Responses Pre- and Post-Dose 5 of DAPTACEL® Vaccination. [Day 0 and between Days 28-48 Post-dose 5]

5. Geometric Mean Titers (GMTs) of Anti-Pertussis, Anti-Diphtheria, and Anti-Tetanus Toxoids Pre- and Post-dose 5 of DAPTACEL® Vaccination [Day 0 and between Days 28-48 post-dose 5]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years to 6 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Aged ≥ 4 and < 7 years from date of birth at the time of study vaccination

• Signed and dated Investigational Review Board (IRB)-approved informed consent from a parent or legally authorized representative. Signed and dated IRB-approved assent from subject if required by IRB

• Judged to be in good health on the basis of reported medical history and physical examination

• Able and willing to attend the scheduled visits and to comply with the study procedures

• Has documented complete infant series and the 4th dose of DAPTACEL® or Pentacel™ in Study P3T06 (i.e., 4 previous administrations of DAPTACEL® or Pentacel™).

Exclusion Criteria:

• Received a 5th dose of DTaP-containing vaccine

• 1. For subjects in the DAPTACEL® arm: Received a 4th dose of Inactivated Poliovirus Vaccine (IPV) vaccine and/or a 2nd dose of Measles, Mumps, and Rubella (MMR) vaccine scheduled at 4 to 6 years of age.

1. For subjects in the Pentacel™ arm: Received a 2nd dose of MMR vaccine scheduled at 4 to 6 years of age

• Severe hypersensitivity to any component of the vaccine such as an anaphylactic reaction observed following a previous vaccination

• Serious underlying chronic disease, including, but not limited to:·Diabetes mellitus; malignancy; cardiopulmonary disease; renal, endocrinologic, or hepatic dysfunction; or hematologic disorder·Unstable or evolving neurologic disorders that may predispose the subject to seizures or neurologic deterioration. These may include progressive neurologic disorders (e.g., infantile spasms, uncontrolled progressive encephalopathy) and encephalopathy within 7 days following previous vaccination

• Known or suspected primary or acquired disease of the immune system

• Administration of immune globulin, other blood products within the last 3 months, injected or oral corticosteroids or other immunomodulator therapy within 6 weeks prior to study vaccination. Individuals on a tapering dose schedule of oral steroids lasting < 7 days may be included in the trial as long as they have not received more than 1 course within the last 2 weeks prior to enrollment

• Had allergy shots started or had changes in regimen or dosing of allergy shots within 4 weeks prior to study vaccination

• Receipt of any other vaccine within 30 days prior to study vaccination, or planning to receive another vaccine within 30 days before the Visit 2 blood draw (if applicable)

• Any other condition which, in the opinion of the investigator, would pose a health risk to the subject or interfere with the evaluation of the vaccine

• Enrolled in another vaccine trial

• Personal history of physician-diagnosed or laboratory-confirmed pertussis disease within the past 30 months

• Known or suspected allergy to any of the vaccines or vaccine components intended for use in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Fayetteville	Arkansas	United States
2		Jonesboro	Arkansas	United States
3		Little Rock	Arkansas	United States
4		Fountain Valley	California	United States
5		Centennial	Colorado	United States
6		Norwich	Connecticut	United States
7		Marietta	Georgia	United States
8		Bardstown,	Kentucky	United States
9		Bossier City	Louisiana	United States
10		Rochester	New York	United States
11		Pembroke	North Carolina	United States
12		Sylva	North Carolina	United States
13		Norristown	Pennsylvania	United States
14		Pittsburgh	Pennsylvania	United States	15213
15		Pittsburgh	Pennsylvania	United States	15241
16		Kingsport	Tennessee	United States
17		Fort Worth	Texas	United States
18		San Antonio	Texas	United States
19		Provo	Utah	United States
20		Spokane	Washington	United States
21		LaCrosse	Wisconsin	United States
22		Marshfield	Wisconsin	United States

Sponsors and Collaborators

• Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Director, Sanofi Pasteur Inc.

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT00258895
• Other Study ID Numbers: P3T11
• First Posted: Nov 28, 2005
• Last Update Posted: Apr 14, 2016
• Last Verified: Apr 1, 2016

• Keywords provided by Sanofi Pasteur, a Sanofi Company: DAPTACEL®; Pentacel™; Diphtheria; Tetanus; Pertussis; Whooping cough; Acellular Pertussis Vaccine Adsorbed
• Additional relevant MeSH terms: Whooping Cough; Tetanus; Diphtheria

Study Results

Participant Flow

Recruitment Details	Participants were enrolled from 30 March 2005 to 02 March 2006 at 22 US sites.
Pre-assignment Detail	A total of 649 participants who met the inclusion and exclusion criteria were enrolled and vaccinated.

Arm/Group Title	DAPTACEL®-Primed	Pentacel®-Primed
Arm/Group Description	Participants received Daptacel in Study P3T06; and a fifth dose of DAPTACEL® vaccine concurrently with a fourth dose of inactivated poliovirus vaccine in this study.	Participants received Pentacel in Study P3T06, received a fifth dose of DAPTACEL® vaccine after 4 doses of Pentacel® vaccine in this study.
Period Title: Overall Study
STARTED	487	162
COMPLETED	477	159
NOT COMPLETED	10	3

Baseline Characteristics

Arm/Group Title	DAPTACEL®-Primed	Pentacel®-Primed	Total
Arm/Group Description	Participants received Daptacel in Study P3T06; and a fifth dose of DAPTACEL® vaccine concurrently with a fourth dose of inactivated poliovirus vaccine in this study.	Participants received Pentacel in Study P3T06, received a fifth dose of DAPTACEL® vaccine after 4 doses of Pentacel® vaccine in this study.	Total of all reporting groups
Overall Participants	487	162	649
Age (Count of Participants)
<=18 years	487 100%	162 100%	649 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	4.1 (0.14)	4.1 (0.16)	4.1 (0.14)
Sex: Female, Male (Count of Participants)
Female	244 50.1%	83 51.2%	327 50.4%
Male	243 49.9%	79 48.8%	322 49.6%
Region of Enrollment (participants) [Number]
United States	487 100%	162 100%	649 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Reporting Solicited Local or Systemic Reactions Post-Dose 5 of DAPTACEL® Vaccination
Time Frame	0 to 7 days Post-Dose 5

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	DAPTACEL®-Primed	Pentacel®-Primed
Arm/Group Description	Participants received Daptacel in Study P3T06; and a fifth dose of DAPTACEL® vaccine concurrently with a fourth dose of inactivated poliovirus vaccine in this study.	Participants received Pentacel in Study P3T06, received a fifth dose of DAPTACEL® vaccine after 4 doses of Pentacel® vaccine in this study.
Measure Participants	485	162
Any Solicited Local Reaction - Dose 5	75 15.4%	70 43.2%
Any Redness (> 5 mm)	36 7.4%	24 14.8%
Grade 3 Redness (> 50 mm)	16 3.3%	9 5.6%
Any Swelling (> 5 mm)	24 4.9%	14 8.6%
Grade 3 Swelling (> 50 mm)	8 1.6%	1 0.6%
Any Tenderness	62 12.7%	55 34%
Grade 3 Tenderness (Incapacitating)	2 0.4%	0 0%
Any Change in Limb Circumference (> 5 mm)	39 8%	32 19.8%
Grade 3 Change in Limb Circumference (> 40 mm)	2 0.4%	0 0%
Any Functional Impairment	20 4.1%	12 7.4%
Grade 3 Functional Impairment (Incapacitating)	0 0%	0 0%
Any Solicited Systemic Reaction - Dose 5	55 11.3%	45 27.8%
Any Fever (≥ 38.0 ºC)	8 1.6%	6 3.7%
Grade 3 Fever (> 39.5 ºC)	0 0%	1 0.6%
Any Irritability	36 7.4%	28 17.3%
Grade 3 Irritability (Incapacitating)	0 0%	0 0%
Any Crying	15 3.1%	11 6.8%
Grade 3 Crying (Incapacitating)	0 0%	0 0%
Any Lethargy	22 4.5%	17 10.5%
Grade 3 Lethargy (Incapacitating)	1 0.2%	1 0.6%
Any Anorexia	16 3.3%	14 8.6%
Grade 3 Anorexia (skipped 2 meals)	1 0.2%	1 0.6%
Any Vomiting (per 24 hours)	4 0.8%	4 2.5%
Grade 3 Vomiting (≥ 3 episodes)	1 0.2%	0 0%
Any Diarrhea (per 24 hours)	8 1.6%	6 3.7%
Grade 3 Diarrhea (> 5 diarrhea stools)	0 0%	0 0%
Any Rash	10 2.1%	5 3.1%

2. Primary Outcome

Title	Percentage of Participants With Anti-Pertussis 4-Fold Rises Post-Dose 5 of DAPTACEL® Vaccination
Description	Anti-Pertussis (anti-Pertussis, anti-Filamentous Haemagglutinin, anti-Fimbriae, and anti-Pertactin) Fold-rise is calculated as post-Dose 5/pre-Dose 5 titer.
Time Frame	Day 28 to 48 Post-dose 5

Outcome Measure Data

Analysis Population Description

The anti-Pertussis 4-fold rises were evaluated in the per-protocol immunology population.

Arm/Group Title	DAPTACEL®-Primed	Pentacel®-Primed
Arm/Group Description	Participants received Daptacel in Study P3T06; and a fifth dose of DAPTACEL® vaccine concurrently with a fourth dose of inactivated poliovirus vaccine in this study.	Participants received Pentacel in Study P3T06, received a fifth dose of DAPTACEL® vaccine after 4 doses of Pentacel® vaccine in this study.
Measure Participants	251	80
Anti-Pertussis (EU/mL)	92 18.9%	98 60.5%
Anti-Filamentous Haemagglutinin (EU/mL)	89 18.3%	89 54.9%
Anti-Fimbriae Types 2 and 3 (EU/mL)	90 18.5%	96 59.3%
Anti-Pertactin (EU/mL)	94 19.3%	95 58.6%

3. Primary Outcome

Title	Percentage of Participants With Anti-Pertussis Booster Response Post-Dose 5 of DAPTACEL® Vaccination
Description	Booster response calculation: If pre-Dose 5 titer < 4x limit of quantitation (LOQ) a 4-fold rise of post-Dose 5/pre-Dose 5. If pre-Dose 5 titer ≥ 4x LOQ a 2-fold rise of post-Dose 5/pre-Dose 5.
Time Frame	Day 28 to 48 Post-Dose 5

Outcome Measure Data

Analysis Population Description

The anti-pertussis booster response was assessed in the per-protocol immunogenicity population.

Arm/Group Title	DAPTACEL®-Primed	Pentacel®-Primed
Arm/Group Description	Participants received Daptacel in Study P3T06; and a fifth dose of DAPTACEL® vaccine concurrently with a fourth dose of inactivated poliovirus vaccine in this study.	Participants received Pentacel in Study P3T06, received a fifth dose of DAPTACEL® vaccine after 4 doses of Pentacel® vaccine in this study.
Measure Participants	251	80
Anti-Pertussis (EU/mL)	96 19.7%	99 61.1%
Anti-Fillamentous Haemagglutinin (EU/mL)	93 19.1%	96 59.3%
Anti-Fimbriae Types 2 and 3 (EU/mL)	96 19.7%	99 61.1%
Anti-Pertactin (EU/mL)	97 19.9%	96 59.3%

4. Primary Outcome

Title	Percentage of Participants With Anti-Diphtheria and Anti-Tetanus Toxoids Responses Pre- and Post-Dose 5 of DAPTACEL® Vaccination.
Time Frame	Day 0 and between Days 28-48 Post-dose 5

Outcome Measure Data

Analysis Population Description

Antibody responses were assessed for each of the antigens in DAPTACEL vaccine in the per-protocol immunogenicity population.

Arm/Group Title	DAPTACEL®-Primed	Pentacel®-Primed
Arm/Group Description	Participants received Daptacel in Study P3T06; and a fifth dose of DAPTACEL® vaccine concurrently with a fourth dose of inactivated poliovirus vaccine in this study.	Participants received Pentacel in Study P3T06, received a fifth dose of DAPTACEL® vaccine after 4 doses of Pentacel® vaccine in this study.
Measure Participants	251	81
Anti-Diphtheria (IU/mL) ≥ 0.01 Pre-dose 5	99 20.3%	99 61.1%
Anti-Diphtheria (IU/mL) ≥ 0.1 Pre-dose 5	47 9.7%	50 30.9%
Anti-Diptheria (IU/mL) ≥ 1.0 Pre-dose 5	1 0.2%	1 0.6%
Anti-Diphtheria (IU/mL) ≥ 0.1 Post-dose 5	100 20.5%	100 61.7%
Anti-Diphtheria (IU/mL) ≥ 1.0 Post-dose 5	100 20.5%	100 61.7%
Anti-Tetanus (IU/mL) ≥ 0.01 Pre-dose 5	100 20.5%	99 61.1%
Anti-Tetanus (IU/mL) ≥ 0.1 Pre-dose 5	85 17.5%	82 50.6%
Anti-Tetanus (IU/mL) ≥ 1.0 Pre-dose 5	20 4.1%	12 7.4%
Anti-Tetanus (IU/mL) ≥ 0.1 Post-dose 5	100 20.5%	100 61.7%
Anti-Tetanus (IU/mL) ≥ 1.0 Post-dose 5	99 20.3%	98 60.5%

5. Primary Outcome

Title	Geometric Mean Titers (GMTs) of Anti-Pertussis, Anti-Diphtheria, and Anti-Tetanus Toxoids Pre- and Post-dose 5 of DAPTACEL® Vaccination
Time Frame	Day 0 and between Days 28-48 post-dose 5

Outcome Measure Data

Analysis Population Description

GMTs were assessed for each of the antigens in DAPTACEL vaccine in the per-protocol immunogenicity population.

Arm/Group Title	DAPTACEL®-Primed	Pentacel®-Primed
Arm/Group Description	Participants received Daptacel in Study P3T06; and a fifth dose of DAPTACEL® vaccine concurrently with a fourth dose of inactivated poliovirus vaccine in this study.	Participants received Pentacel in Study P3T06, received a fifth dose of DAPTACEL® vaccine after 4 doses of Pentacel® vaccine in this study.
Measure Participants	255	81
Anti-Pertussis (EU/mL) Pre-Dose	7.67	9.80
Anti-Pertussis (EU/mL) Post-Dose	154.32	180.77
Anti-Filamentous Haemagglutinin (EU/mL) Pre-Dose	5.03	7.52
Anti-Filamentous Haemagglutinin (EU/mL) Post-Dose	82.11	120.03
Anti-Fimbriae Types 2 and 3 (EU/mL) Pre-dose	24.45	34.50
Anti-Fimbriae Types 2 and 3 (EU/mL) Post-dose	450.56	649.86
Anti-Pertactin (EU/mL) Pre-dose	15.62	9.16
Anti-Pertactin (EU/mL) Post-dose	229.59	148.80
Anti-Diphtheria (IU/mL) Pre-dose	0.11	0.11
Anti-Diphtheria (IU/mL) Post-dose	19.59	22.56
Anti-Tetanus (IU/mL) Pre-dose	0.38	0.27
Anti-Tetanus (IU/mL) Post-dose	6.21	4.47

Adverse Events

Time Frame	Adverse events data were collected from the day of vaccination for 6 months post-vaccination.
Arm/Group Title	DAPTACEL®-Primed		Pentacel®-Primed
Arm/Group Description	Participants received Daptacel in Study P3T06; and a fifth dose of DAPTACEL® vaccine concurrently with a fourth dose of inactivated poliovirus vaccine in this study.		Participants received Pentacel in Study P3T06, received a fifth dose of DAPTACEL® vaccine after 4 doses of Pentacel® vaccine in this study.
All Cause Mortality
	DAPTACEL®-Primed		Pentacel®-Primed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	DAPTACEL®-Primed		Pentacel®-Primed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/487 (1%)		3/162 (1.9%)
Blood and lymphatic system disorders
Thrombocytopenic purpura	0/487 (0%)	0	1/162 (0.6%)	1
Cardiac disorders
Supraventricular tachycardia	0/487 (0%)	0	1/162 (0.6%)	1
Infections and infestations
Gastroenteritis NOS	0/487 (0%)	0	2/162 (1.2%)	2
Otitis media NOS	1/487 (0.2%)	1	0/162 (0%)	0
Pneumonia respiratory syncytial viral	1/487 (0.2%)	1	0/162 (0%)	0
Injury, poisoning and procedural complications
Head injury	1/487 (0.2%)	1	0/162 (0%)	0
Skull fracture NOS	1/487 (0.2%)	1	0/162 (0%)	0
Metabolism and nutrition disorders
Dehydration	0/487 (0%)	0	1/162 (0.6%)	1
Psychiatric disorders
Staring	1/487 (0.2%)	1	0/162 (0%)	0
Respiratory, thoracic and mediastinal disorders
Hypoxia	1/487 (0.2%)	1	0/162 (0%)	0
Bronchospasm NOS	1/487 (0.2%)	1	0/162 (0%)	0
Skin and subcutaneous tissue disorders
Asthma NOS	2/487 (0.4%)	2	0/162 (0%)	0
Other (Not Including Serious) Adverse Events
	DAPTACEL®-Primed		Pentacel®-Primed
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	62/487 (12.7%)		55/162 (34%)
Gastrointestinal disorders
Lethargy	22/487 (4.5%)		17/162 (10.5%)
General disorders
Injection site redness	36/487 (7.4%)		24/162 (14.8%)
Injection site swelling	24/487 (4.9%)		14/162 (8.6%)
Injection site tenderness	62/487 (12.7%)		55/162 (34%)
Infections and infestations
Otitis media NOS	24/487 (4.9%)		9/162 (5.6%)
Upper respiratory tract infection NOS	34/487 (7%)		7/162 (4.3%)
Musculoskeletal and connective tissue disorders
Anorexia	16/487 (3.3%)		14/162 (8.6%)
Psychiatric disorders
Irritability	36/487 (7.4%)		28/162 (17.3%)
Crying	15/487 (3.1%)		11/162 (6.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.