Study of DTaP-IPV-Hep B-PRP~T Combined Vaccine Compared to Infanrix®Hexa in Healthy Peruvian Infants

• ClinicalTrials.gov Identifier: NCT00831753
• Recruitment Status: Completed
• First Posted: January 29, 2009
• Results First Posted: April 2, 2014
• Last Update Posted: May 13, 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: Single (Outcomes Assessor); Primary Purpose: Prevention
• Conditions: Diphtheria; Tetanus; Pertussis; Haemophilus Influenzae Type b; Hepatitis B
• Interventions: Biological: DTaP IPV HB PRP~T vaccine; Biological: DTaP-HB-IPV and Haemophilus influenzae type b
• Enrollment: 263

Participant Flow

Recruitment Details	Participants were enrolled from 23 May 2008 to 18 July 2008 at 1 clinical center in Peru.
Pre-assignment Details	A total of 263 participants who met the inclusion and exclusion criteria were randomized and vaccinated in the study.

Arm/Group Title	DTaP-IPV-Hep B-PRP~T Group	Infanrix Hexa™ Group
Arm/Group Description	All participants received a 3-dose primary series of diphtheria, tetanus, pertussis (2-component acellular), recombinant hepatitis B (Hep B) Hansenula polymorpha and inactivated poliomyelitis vaccine (IPV) adsorbed, and Haemophilus influenzae type b (Hib) vaccine, polyribosyl ribitol phosphate conjugated to tetanus protein (DTaP-IPV-Hep B-PRP~T) combined vaccine. A dose at 2, 4, and 6 months of age, respectively.	All participants received a 3-dose primary series of Infanrix hexa™ vaccine, with 1 dose each at 2, 4, and 6 months of age, respectively.
Period Title: Overall Study
Started	132	131
Completed	132	131
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		DTaP-IPV-Hep B-PRP~T Group	Infanrix Hexa™ Group	Total
Arm/Group Description		All participants received a 3-dose primary series of diphtheria, tetanus, pertussis (2-component acellular), recombinant hepatitis B (Hep B) Hansenula polymorpha and inactivated poliomyelitis vaccine (IPV) adsorbed, and Haemophilus influenzae type b (Hib) vaccine, polyribosyl ribitol phosphate conjugated to tetanus protein (DTaP-IPV-Hep B-PRP~T) combined vaccine. A dose at 2, 4, and 6 months of age, respectively.	All participants received a 3-dose primary series of Infanrix hexa™ vaccine, with 1 dose each at 2, 4, and 6 months of age, respectively.	Total of all reporting groups
Overall Number of Baseline Participants		132	131	263
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	132 participants	131 participants	263 participants
	<=18 years	132 100.0%	131 100.0%	263 100.0%
	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	132 participants	131 participants	263 participants
		1.75 (0.132)	1.72 (0.123)	1.74 (0.128)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	132 participants	131 participants	263 participants
	Female	58 43.9%	74 56.5%	132 50.2%
	Male	74 56.1%	57 43.5%	131 49.8%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
Peru	Number Analyzed	132 participants	131 participants	263 participants
		132	131	263

Outcome Measures

1. Primary Outcome

Title	Number of Participants Achieving Seroprotection for Anti Hep-B After a Primary Series of Vaccination With Either DTaP-IPV-Hep B-PRP~T or Infanrix Hexa™
Description	Anti-hepatitis B (Hep B) antibodies were measured by chemiluminescence detection. Seroprotection was defined as a titer ≥ 10 mIU/mL.
Time Frame	Day 150 (1 month after dose 3)

Outcome Measure Data

Analysis Population Description

Seroprotection against Hep B was assessed in all participants who did not have any protocol violation that might have interfered with primary criteria evaluation (Per-Protocol Population).

Arm/Group Title	DTaP-IPV-Hep B-PRP~T Group	Infanrix Hexa™ Group
Arm/Group Description:	All participants received a 3-dose primary series of diphtheria, tetanus, pertussis (2-component acellular), recombinant hepatitis B (Hep B) Hansenula polymorpha and inactivated poliomyelitis vaccine (IPV) adsorbed, and Haemophilus influenzae type b (Hib) vaccine, polyribosyl ribitol phosphate conjugated to tetanus protein (DTaP-IPV-Hep B-PRP~T) combined vaccine. A dose at 2, 4, and 6 months of age, respectively.	All participants received a 3-dose primary series of Infanrix hexa™ vaccine, with 1 dose each at 2, 4, and 6 months of age, respectively.
Overall Number of Participants Analyzed	132	130
Measure Type: Number; Unit of Measure: Participants
	131	130

2. Primary Outcome

Title	Number of Participants Achieving Seroprotection to Vaccine Antigens After a Primary Series Vaccination With Either DTaP-IPV-Hep B-PRP~T or Infanrix Hexa™ Vaccine.
Description	Antibody titers were measured by chemiluminescence detection for hepatitis B (Hep B), by Farr type radioimmunoassay for Haemophilus influenzae type b (PRP), and by toxin neutralization test for diphtheria. Seroprotection criteria were defined as: Criteria 1: Anti-Hep B titer ≥ 10 mIU/mL; Anti-PRP titer ≥ 0.15 µg/mL; Anti-diphtheria titer ≥ 0.01 IU/mL. Criteria 2: Anti-Hep B titer ≥ 100 mIU/mL; Anti-PRP titer ≥ 1 µg/mL; Anti-diphtheria titer or ≥ 0.1 IU/mL.
Time Frame	Day 150 (1 month after dose 3)

Outcome Measure Data

Analysis Population Description

Seroprotection was assessed in all participants who did not have any protocol violation that might have interfered with primary criteria evaluation (Per-Protocol Population).

Arm/Group Title	DTaP-IPV-Hep B-PRP~T Group	Infanrix Hexa™ Group
Arm/Group Description:	All participants received a 3-dose primary series of diphtheria, tetanus, pertussis (2-component acellular), recombinant hepatitis B (Hep B) Hansenula polymorpha and inactivated poliomyelitis vaccine (IPV) adsorbed, and Haemophilus influenzae type b (Hib) vaccine, polyribosyl ribitol phosphate conjugated to tetanus protein (DTaP-IPV-Hep B-PRP~T) combined vaccine. A dose at 2, 4, and 6 months of age, respectively.	All participants received a 3-dose primary series of Infanrix hexa™ vaccine, with 1 dose each at 2, 4, and 6 months of age, respectively.
Overall Number of Participants Analyzed	132	130
Measure Type: Number; Unit of Measure: Participants
Anti-Hep B (Criteria 1)	131	130
Anti-Hep B (Criteria 2)	124	129
Anti-PRP (Criteria 1)	132	129
Anti-PRP (Criteria 2)	112	109
Anti-Diphtheria (Criteria 1)	126	130
Anti-Diphtheria (Criteria 2)	77	85

3. Secondary Outcome

Title	Geometric Mean Titers (GMTs) of Antibodies to Vaccine Antigens After a Primary Series of Vaccination With Either DTaP-IPV-Hep B-PRP~T or Infanrix Hexa™ Vaccine.
Description	Antibody titers were measured by chemiluminescence detection for hepatitis B (Hep B), by Farr type radioimmunoassay for Haemophilus influenzae type b (PRP), and by toxin neutralization test for diphtheria.
Time Frame	Day 150 (1 month after dose 3)

Outcome Measure Data

Analysis Population Description

Antibody GMTs were assessed in all participants who did not have any protocol violation that might have interfered with primary criteria evaluation (Per-Protocol Population).

Arm/Group Title	DTaP-IPV-Hep B-PRP~T Group	Infanrix Hexa™ Group
Arm/Group Description:	All participants received a 3-dose primary series of diphtheria, tetanus, pertussis (2-component acellular), recombinant hepatitis B (Hep B) Hansenula polymorpha and inactivated poliomyelitis vaccine (IPV) adsorbed, and Haemophilus influenzae type b (Hib) vaccine, polyribosyl ribitol phosphate conjugated to tetanus protein (DTaP-IPV-Hep B-PRP~T) combined vaccine. A dose at 2, 4, and 6 months of age, respectively.	All participants received a 3-dose primary series of Infanrix hexa™ vaccine, with 1 dose each at 2, 4, and 6 months of age, respectively.
Overall Number of Participants Analyzed	132	130
Geometric Mean (95% Confidence Interval); Unit of Measure: Titers (1/dilutions)
Anti Hep B	986; (764 to 1270)	1139; (961 to 1350)
Anti PRP	5.22; (4.04 to 6.73)	3.93; (3.17 to 4.89)
Anti Diphtheria	0.156; (0.119 to 0.204)	0.192; (0.154 to 0.239)

4. Secondary Outcome

Title	Number of Participants Reporting Solicited Injection Site or Solicited Systemic Reactions After Vaccination With Either DTaP-IPV-Hep B-PRP~T or Infanrix Hexa™ Vaccine.
Description	Solicited Injection Site Reactions: Pain, Erythema, Swelling. Solicited Systemic Reactions: Pyrexia (Temperature), Vomiting, Crying, Somnolence, Anorexia, Irritability. Grade 3 reactions were defined as: Pain, cries when injected limb is moved or movement of injected limb is reduced; Erythema and Swelling ≥ 5 cm; Pyrexia > 39.5ºC; Vomiting ≥ 6 episodes per 24 hour or requiring parenteral hydration; Crying, > 3 hours; Somnolence, sleeping most of the time or difficult to wake up; Anorexia refuses ≥ 3 feeds/meals or refuses most feeds/meals; Irritability inconsolable.
Time Frame	Day 0 up to Day 7 after each injection

Outcome Measure Data

Analysis Population Description

Solicited reactions were assessed in all participants who received at least one dose of investigational or control vaccine, according to the vaccine actually received (Safety Analysis Population).

Arm/Group Title	DTaP-IPV-Hep B-PRP~T Group	Infanrix Hexa™ Group
Arm/Group Description:	All participants received a 3-dose primary series of diphtheria, tetanus, pertussis (2-component acellular), recombinant hepatitis B (Hep B) Hansenula polymorpha and inactivated poliomyelitis vaccine (IPV) adsorbed, and Haemophilus influenzae type b (Hib) vaccine, polyribosyl ribitol phosphate conjugated to tetanus protein (DTaP-IPV-Hep B-PRP~T) combined vaccine. A dose at 2, 4, and 6 months of age, respectively.	All participants received a 3-dose primary series of Infanrix hexa™ vaccine, with 1 dose each at 2, 4, and 6 months of age, respectively.
Overall Number of Participants Analyzed	132	131
Measure Type: Number; Unit of Measure: Participants
Pain Post Injection 1	82	71
Pain Post Injection 2	68	68
Pain Post Injection 3	53	55
Grade 3 Pain Post Any Injection	10	6
Erythema Post Injection 1	32	16
Erythema Post Injection 2	48	30
ErythemaPost Injection 3	45	46
Grade 3 Erythema Post Any Injection	3	5
Swelling Post Injection 1	34	12
Swelling Post Injection 2	26	24
Swelling Post Injection 3	28	32
Grade 3 Swelling Post Any Injection	3	2
Pyrexia Post Injection 1	11	11
Pyrexia Post Injection 2	21	17
Pyrexia Post Injection 3	18	18
Gade 3 Pyrexia Post Any Injection	0	3
Any Vomiting Post Injection 1	20	24
Any Vomiting Post Injection 2	8	6
Vomiting Post Injection 3	6	10
Grade 3 Vomiting Post Any Injection	0	0
Crying Post Injection 1	81	68
Crying Post Injection 2	57	52
Crying Post Injection 3	43	47
Grade 3 Crying Post Any Injection	1	1
Somnolence Post Injection 1	55	65
Somnolence Post Injection 2	41	37
Somnolence Post Injection 3	23	28
Grade 3 Somnolence Post Any Injection	2	2
Any Anorexia Post Injection 1	35	42
Anorexia Post Injection 2	24	22
Anorexia Post Injection 3	24	25
Grade 3 Anorexia Post Any Injection	0	1
Irritability Post Injection 1	85	81
Irritability Post Injection 2	63	65
Irritability Post Injection 3	40	55
Grade 3 Irritability Post Any Injection	2	1

Adverse Events

Time Frame	Adverse events data were collected from Day 0 after the first injection to up to 30 days after each injection.
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	DTaP-IPV-Hep B-PRP~T Group		Infanrix Hexa™ Group
Arm/Group Description	All participants received a 3-dose primary series of diphtheria, tetanus, pertussis (2-component acellular), recombinant hepatitis B (Hep B) Hansenula polymorpha and inactivated poliomyelitis vaccine (IPV) adsorbed, and Haemophilus influenzae type b (Hib) vaccine, polyribosyl ribitol phosphate conjugated to tetanus protein (DTaP-IPV-Hep B-PRP~T) combined vaccine. A dose at 2, 4, and 6 months of age, respectively.		All participants received a 3-dose primary series of Infanrix hexa™ vaccine, with 1 dose each at 2, 4, and 6 months of age, respectively.
All-Cause Mortality
	DTaP-IPV-Hep B-PRP~T Group		Infanrix Hexa™ Group
	Affected / at Risk (%)		Affected / at Risk (%)
Total	--/--		--/--
Serious Adverse Events
	DTaP-IPV-Hep B-PRP~T Group		Infanrix Hexa™ Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/132 (2.27%)		2/131 (1.53%)
Hepatobiliary disorders
Hepatic Cyst * 1	0/132 (0.00%)	0	1/131 (0.76%)	1
Infections and infestations
Cellulitis * 1	1/132 (0.76%)	1	0/131 (0.00%)	0
Pneumonia Viral * 1	1/132 (0.76%)	1	0/131 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Bronchial Obstruction * 1	1/132 (0.76%)	1	1/131 (0.76%)	1
* Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 10.0
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5.00%
	DTaP-IPV-Hep B-PRP~T Group		Infanrix Hexa™ Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	102/132 (77.27%)		106/131 (80.92%)
Gastrointestinal disorders
Abdominal Pain * 1	38/132 (28.79%)	61	44/131 (33.59%)	65
Diarrhea * 1	17/132 (12.88%)	19	18/131 (13.74%)	21
Vomiting † 1	29/132 (21.97%)	29	32/131 (24.43%)	32
General disorders
Injection Site Hemorrhage * 1	8/132 (6.06%)	9	4/131 (3.05%)	4
Injection Site Pain † 1	102/132 (77.27%)	102	101/131 (77.10%)	101
Injection Site Erythema † 1	78/132 (59.09%)	78	66/131 (50.38%)	66
Injection Site Swelling † 1	54/132 (40.91%)	54	52/131 (39.69%)	52
Irritability † 1	100/132 (75.76%)	100	98/131 (74.81%)	98
Pyrexia † 1	37/132 (28.03%)	37	36/131 (27.48%)	36
Pyrexia * 1	11/132 (8.33%)	13	7/131 (5.34%)	7
Infections and infestations
Nasopharyngitis * 1	62/132 (46.97%)	78	80/131 (61.07%)	118
Pharyngitis * 1	11/132 (8.33%)	11	15/131 (11.45%)	15
Anorexia † 1	54/132 (40.91%)	54	58/131 (44.27%)	58
Nervous system disorders
Somnolence † 1	73/132 (55.30%)	73	82/131 (62.60%)	82
Psychiatric disorders
Crying † 1	100/132 (75.76%)	100	93/131 (70.99%)	93
Respiratory, thoracic and mediastinal disorders
Bronchospasm * 1	13/132 (9.85%)	14	12/131 (9.16%)	14
Cough * 1	14/132 (10.61%)	16	18/131 (13.74%)	24
Skin and subcutaneous tissue disorders
Dermatitis * 1	9/132 (6.82%)	9	6/131 (4.58%)	6
Dermatitis Diaper * 1	14/132 (10.61%)	15	10/131 (7.63%)	10
† Indicates events were collected by systematic assessment; * Indicates events were collected by non-systematic assessment; 1 Term from vocabulary, MedDRA 10.0

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: NCT00831753
• Other Study ID Numbers: A3L17
• First Submitted: January 27, 2009
• First Posted: January 29, 2009
• Results First Submitted: February 14, 2014
• Results First Posted: April 2, 2014
• Last Update Posted: May 13, 2016