Wyeth Study To Evaluate a 13-valent Pneumococcal Conjugate Vaccine in Infants

• Sponsor: Wyeth is now a wholly owned subsidiary of Pfizer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00464945
• Collaborator: (none)
• Enrollment: 269
• Locations: 9
• Arms: 2
• Duration (Months): 15
• Patients Per Site: 29.9
• Patients Per Site Per Month: 2

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the safety, tolerability and immunogenicity of manufacturing scale 13-valent pneumococcal conjugate (13vPnC) vaccine compared to pilot scale 13vPnC in healthy infants when given with routine pediatric vaccines.

Condition or Disease	Intervention/Treatment	Phase
Pneumococcal Vaccines	Biological: 13-valent Pneumococcal Conjugate Vaccine	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 269 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Phase 3, Randomised,Active-Controlled ,Double-Blind Trial Evaluating the Safety, Tolerability, and Immunogenicity of Manufacturing Scale 13-valent Pneumococcal Conjugate Vaccine
• Study Start Date: Jun 1, 2007
• Actual Primary Completion Date: Sep 1, 2008
• Actual Study Completion Date: Sep 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1	Biological: 13-valent Pneumococcal Conjugate Vaccine; 1 dose at 2,3,4 and 12 months of age
Active Comparator: 2	Biological: 13-valent Pneumococcal Conjugate Vaccine; 1 dose at 2,3,4 and 12 months of age

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Achieving Antibody Level ≥0.35μg/mL in 13vPnC Manufacturing Scale Group Relative to 13vPnC Pilot Scale Group After the 3-Dose Infant Series [One month after 3-dose infant series (5 months of age)]

   Percentages of participants achieving WHO predefined antibody threshold ≥0.35μg/mL along with the corresponding 95% CI for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) are presented.

2. Percentage of Participants Reporting Pre-Specified Local Reactions [During the 4-day period after each dose]

   Local reactions were reported using an electronic diary. Tenderness was scaled as Any (tenderness present); Significant(Sig) (present and interfered with limb movement). Induration and erythema were scaled as Any (induration or erythema present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (Mod) (2.5 to 7.0 cm); Severe (> 7.0 cm). Participants may be represented in more than 1 category.

3. Percentage of Participants Reporting Pre-Specified Systemic Events (Infant Series) [During the 4-day period after each dose]

   Systemic events (fever ≥ 38 degrees Celsius [C] but ≤ 39 C, fever >39 C but ≤ 40 C, fever > 40 C, decreased appetite, irritability, increased sleep, decreased sleep, use of medication (Meds)to prevent symptoms (sx), and use of medication to treat symptoms) were collected using an electronic diary. Participants may be represented in more than 1 category.

4. Percentage of Participants Reporting Pre-Specified Systemic Events (Toddler Series) [During the 4-day period after toddler dose]

   Systemic events (fever ≥ 38 degrees Celsius [C] but ≤ 39 C, fever >39 C but ≤ 40 C, fever > 40 C), decreased appetite, irritability, increased sleep, decreased sleep, use of medication to prevent symptoms, and use of medication to treat symptoms) were collected using an electronic diary. Participants may be represented in more than 1 category.

5. Geometric Mean Antibody Concentration in 13vPnC Manufacturing Scale Group Relative to 13vPnC Pilot Scale Group After the 3-Dose Infant Series [One month after 3-dose infant series (5 months of age)]

   Antibody concentration/geometric mean concentration (GMC) as measured by enzyme-linked immunosorbent assay (ELISA) for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (Serotypes 1, 3, 5, 6A, 7F, and 19A) are presented.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 41 Days to 99 Days
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion criteria:

1. Aged 2 months (42 to 98 days) at time of enrollment.

2. Available for entire study period and whose parent/legal guardian can be reached by telephone.

3. Healthy infant as determined by medical history, physical examination, and judgment of the investigator.

4. Parent/legal guardian must be able to complete all relevant study procedures during study participation.

Exclusion criteria:

1. Previous vaccination with licensed or investigational pneumococcal, Hib conjugate, diphtheria, tetanus, pertussis, or polio vaccines.

2. A previous anaphylactic reaction to any vaccine or vaccine-related component.

3. Contraindication to vaccination with Hib conjugate, diphtheria, tetanus, pertussis, polio, hepatitis B, measles, mumps, rubella, or pneumococcal vaccines.

4. Bleeding diathesis or condition associated with prolonged bleeding time that would contraindicate intramuscular injection.

5. Known or suspected immune deficiency or suppression.

6. History of culture-proven invasive disease caused by S pneumoniae.

7. Major known congenital malformation or serious chronic disorders.

8. Significant neurological disorder or history of seizure including febrile seizure, or significant stable or evolving disorders such as cerebral palsy, encephalopathy, hydrocephalus, or other significant disorders. Does not include resolving syndromes due to birth trauma such as Erb palsy.

9. Receipt of blood products or gamma-globulin (including hepatitis B immunoglobulin and monoclonal antibodies; eg, Synagis®).

10. Participation in another investigational or interventional trial. Participation in purely observational studies is acceptable.

11. Infant who is a direct descendant (child or grandchild) of a member of the study site personnel.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Torun	Bydgoszcz	Poland	87-100
2		Siemianowice Slaskie	Krakow	Poland	41-103
3		Lubartowie	Lublin	Poland	21-100
4		Krakow		Poland	30-663
5		Krakow		Poland	31-442
6		Lodz		Poland	91-347
7		Lodz		Poland	93-338
8		Lublin		Poland	20-044
9		Warszawa		Poland	01-184

Sponsors and Collaborators

• Wyeth is now a wholly owned subsidiary of Pfizer

Investigators

• Study Director: Medical Monitor, Wyeth is now a wholly owned subsidiary of Pfizer
• Principal Investigator: Trial Manager, For Poland, [e-mail]

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Wyeth is now a wholly owned subsidiary of Pfizer
• ClinicalTrials.gov Identifier: NCT00464945
• Other Study ID Numbers: 6096A1-3000
• First Posted: Apr 24, 2007
• Last Update Posted: Aug 15, 2012
• Last Verified: Jul 1, 2012

• Additional relevant MeSH terms: Heptavalent Pneumococcal Conjugate Vaccine

Study Results

Participant Flow

Recruitment Details	Participants were recruited in Poland from June 2007 to August 2007.
Pre-assignment Detail	Participants were enrolled into the study according to inclusion/exclusion criteria without a screening period.

Arm/Group Title	13vPnC Manufacturing	13vPnC Pilot
Arm/Group Description	Participants received one single 0.5mL manufacturing scale dose of 13-valent pneumococcal conjugate vaccine (13vPnC) coadministered with combined diphtheria, tetanus, and acellular pertussis inactivated poliovirus, and hemophilus influenza type b vaccine (DTaP-IPV-Hib) and hepatitis B virus vaccine (HBV) at 2 months (infant series, dose 1). Participants received one single 0.5mL manufacturing scale dose of 13vPnC coadministered with DTaP-IPV-Hib at 3 and 4 months (infant series, dose 2 and 3). Participants received one single 0.5mL manufacturing scale dose of 13vPnC coadministered with measles, mumps, and rubella vaccine (MMR) and 12 months of age (toddler dose).	Participants received one single 0.5mL pilot scale dose of 13-valent pneumococcal conjugate vaccine (13vPnC) coadministered with combined diphtheria, tetanus, and acellular pertussis inactivated poliovirus, and hemophilus influenza type b vaccine (DTaP-IPV-Hib) and hepatitis B virus vaccine (HBV) at 2 months (infant series, dose 1). Participants received one single 0.5mL pilot scale dose of 13vPnC coadministered with DTaP-IPV-Hib at 3 and 4 months (infant series, dose 2 and 3). Participants received one single 0.5mL pilot scale dose of 13vPnC coadministered with measles, mumps, and rubella vaccine (MMR) and 12 months of age (toddler dose).
Period Title: Infant Series
STARTED	135	134
Vaccinated Dose 1	134	134
Vaccinated Dose 2	132	133
Vaccinated Dose 3	132	133
COMPLETED	131	133
NOT COMPLETED	4	1
Period Title: Infant Series
STARTED	131	133
COMPLETED	131	131
NOT COMPLETED	0	2
Period Title: Infant Series
STARTED	131	131
COMPLETED	131	130
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	13vPnC Manufacturing	13vPnC Pilot	Total
Arm/Group Description	Participants received one single 0.5mL manufacturing scale dose of 13-valent pneumococcal conjugate vaccine (13vPnC) coadministered with combined diphtheria, tetanus, and acellular pertussis inactivated poliovirus, and hemophilus influenza type b vaccine (DTaP-IPV-Hib) and hepatitis B virus vaccine (HBV) at 2 months (infant series, dose 1). Participants received one single 0.5mL manufacturing scale dose of 13vPnC coadministered with DTaP-IPV-Hib at 3 and 4 months (infant series, dose 2 and 3). Participants received one single 0.5mL manufacturing scale dose of 13vPnC coadministered with measles, mumps, and rubella vaccine (MMR) and 12 months of age (toddler dose).	Participants received one single 0.5mL pilot scale dose of 13-valent pneumococcal conjugate vaccine (13vPnC) coadministered with combined diphtheria, tetanus, and acellular pertussis inactivated poliovirus, and hemophilus influenza type b vaccine (DTaP-IPV-Hib) and hepatitis B virus vaccine (HBV) at 2 months (infant series, dose 1). Participants received one single 0.5mL pilot scale dose of 13vPnC coadministered with DTaP-IPV-Hib at 3 and 4 months (infant series, dose 2 and 3). Participants received one single 0.5mL pilot scale dose of 13vPnC coadministered with measles, mumps, and rubella vaccine (MMR) and 12 months of age (toddler dose).	Total of all reporting groups
Overall Participants	135	134	269
Age (months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [months]	2.1 (0.6)	2.1 (0.5)	2.1 (0.5)
Sex: Female, Male (Count of Participants)
Female	65 48.1%	67 50%	132 49.1%
Male	70 51.9%	67 50%	137 50.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Achieving Antibody Level ≥0.35μg/mL in 13vPnC Manufacturing Scale Group Relative to 13vPnC Pilot Scale Group After the 3-Dose Infant Series
Description	Percentages of participants achieving WHO predefined antibody threshold ≥0.35μg/mL along with the corresponding 95% CI for the 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (serotypes 1, 3, 5, 6A, 7F, and 19A) are presented.
Time Frame	One month after 3-dose infant series (5 months of age)

Outcome Measure Data

Analysis Population Description

Evaluable immunogenicity (per protocol) population consisting of eligible participants who adhered to protocol requirements, had valid and determinate assay results, and had no other major protocol violations.

Arm/Group Title	13vPnC Manufacturing	13vPnC Pilot
Arm/Group Description	Participants received one single 0.5mL manufacturing scale dose of 13-valent pneumococcal conjugate vaccine (13vPnC) coadministered with combined diphtheria, tetanus, and acellular pertussis inactivated poliovirus, and hemophilus influenza type b vaccine (DTaP-IPV-Hib) and hepatitis B virus vaccine (HBV) at 2 months (infant series, dose 1). Participants received one single 0.5mL manufacturing scale dose of 13vPnC coadministered with DTaP-IPV-Hib at 3 and 4 months (infant series, dose 2 and 3). Participants received one single 0.5mL manufacturing scale dose of 13vPnC coadministered with measles, mumps, and rubella vaccine (MMR) and 12 months of age (toddler dose).	Participants received one single 0.5mL pilot scale dose of 13-valent pneumococcal conjugate vaccine (13vPnC) coadministered with combined diphtheria, tetanus, and acellular pertussis inactivated poliovirus, and hemophilus influenza type b vaccine (DTaP-IPV-Hib) and hepatitis B virus vaccine (HBV) at 2 months (infant series, dose 1). Participants received one single 0.5mL pilot scale dose of 13vPnC coadministered with DTaP-IPV-Hib at 3 and 4 months (infant series, dose 2 and 3). Participants received one single 0.5mL pilot scale dose of 13vPnC coadministered with measles, mumps, and rubella vaccine (MMR) and 12 months of age (toddler dose).
Measure Participants	128	131
Common Serotypes-Serotype 4	97.7 72.4%	96.9 72.3%
Common Serotypes-Serotype 6B	77.3 57.3%	74.0 55.2%
Common Serotypes-Serotype 9V	98.4 72.9%	96.2 71.8%
Common Serotypes-Serotype 14	92.9 68.8%	94.5 70.5%
Common Serotypes-Serotype 18C	96.1 71.2%	93.1 69.5%
Common Serotypes-Serotype 19F	98.4 72.9%	97.7 72.9%
Common Serotypes-Serotype 23F	82.8 61.3%	81.7 61%
Additional Serotypes-Serotype 1	93.0 68.9%	90.8 67.8%
Additional Serotypes-Serotype 3	93.7 69.4%	95.4 71.2%
Additional Serotypes-Serotype 5	90.6 67.1%	88.5 66%
Additional Serotypes-Serotype 6A	85.2 63.1%	86.3 64.4%
Additional Serotypes-Serotype 7F	100.0 74.1%	100.0 74.6%
Additional Serotypes-Serotype 19A	99.2 73.5%	99.2 74%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 4 the difference in percentages between the two groups (13vPnC Manufacturing - 13vPnC Pilot) was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.7
	Confidence Interval	() 95%; -3.9 to 5.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 6B the difference in percentages between the two groups (13vPnC Manufacturing - 13vPnC Pilot) was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	3.3
	Confidence Interval	() 95%; -7.3 to 13.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 9V the difference in percentages between the two groups (13vPnC Manufacturing - 13vPnC Pilot) was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	2.3
	Confidence Interval	() 95%; -2.1 to 7.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 14 the difference in percentages between the two groups (13vPnC Manufacturing - 13vPnC Pilot) was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-1.6
	Confidence Interval	() 95%; -8.2 to 4.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 18C the difference in percentages between the two groups (13vPnC Manufacturing - 13vPnC Pilot) was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	3.0
	Confidence Interval	() 95%; -2.8 to 9.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 19F the difference in percentages between the two groups (13vPnC Manufacturing - 13vPnC Pilot) was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.7
	Confidence Interval	() 95%; -3.5 to 5.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 23F the difference in percentages between the two groups (13vPnC Manufacturing - 13vPnC Pilot) was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	1.1
	Confidence Interval	() 95%; -8.4 to 10.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 1 the difference in percentages between the two groups (13vPnC Manufacturing - 13vPnC Pilot) was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	2.1
	Confidence Interval	() 95%; -4.8 to 9.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 3 the difference in percentages between the two groups (13vPnC Manufacturing - 13vPnC Pilot) was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-1.7
	Confidence Interval	() 95%; -7.9 to 4.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 5 the difference in percentages between the two groups (13vPnC Manufacturing - 13vPnC Pilot) was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	2.1
	Confidence Interval	() 95%; -5.6 to 9.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 6A the difference in percentages between the two groups (13vPnC Manufacturing - 13vPnC Pilot) was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-1.1
	Confidence Interval	() 95%; -9.9 to 7.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 7F the difference in percentages between the two groups (13vPnC Manufacturing - 13vPnC Pilot) was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	0.0
	Confidence Interval	() 95%; -3.0 to 2.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 19A the difference in percentages between the two groups (13vPnC Manufacturing - 13vPnC Pilot) was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-0.0
	Confidence Interval	() 95%; -3.6 to 3.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percentage of Participants Reporting Pre-Specified Local Reactions
Description	Local reactions were reported using an electronic diary. Tenderness was scaled as Any (tenderness present); Significant(Sig) (present and interfered with limb movement). Induration and erythema were scaled as Any (induration or erythema present); Mild (0.5 centimeters [cm] to 2.0 cm); Moderate (Mod) (2.5 to 7.0 cm); Severe (> 7.0 cm). Participants may be represented in more than 1 category.
Time Frame	During the 4-day period after each dose

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least 1 dose of vaccine; (n) = number of participants reporting yes for at least 1 day or no for all days.

Arm/Group Title	13vPnC Manufacturing Dose 1	13vPnC Pilot Dose 1	13vPnC Manufacturing Dose 2	13vPnC Pilot Dose 2	13vPnC Manufacturing Dose 3	13vPnC Pilot Dose 3	13vPnC Manufacturing Toddler Dose	13vPnC Pilot Toddler Dose
Arm/Group Description	Participants received one single 0.5mL manufacturing scale dose of 13-valent pneumococcal conjugate vaccine (13vPnC) coadministered with combined diphtheria, tetanus, and acellular pertussis inactivated poliovirus, and hemophilus influenza type b vaccine (DTaP-IPV-Hib) and hepatitis B virus vaccine (HBV) at 2 months (infant series, dose 1).	Participants received one single 0.5mL pilot scale dose of 13-valent pneumococcal conjugate vaccine (13vPnC) coadministered with combined diphtheria, tetanus, and acellular pertussis inactivated poliovirus, and hemophilus influenza type b vaccine (DTaP-IPV-Hib) and hepatitis B virus vaccine (HBV) at 2 months (infant series, dose 1).	Participants received one single 0.5mL manufacturing scale dose of 13vPnC coadministered with DTaP-IPV-Hib at 3 and 4 months (infant series, dose 2 and 3).	Participants received one single 0.5mL pilot scale dose of 13vPnC coadministered with DTaP-IPV-Hib at 3 and 4 months (infant series, dose 2 and 3).	Participants received one single 0.5mL manufacturing scale dose of 13vPnC coadministered with DTaP-IPV-Hib at 3 and 4 months (infant series, dose 2 and 3).	Participants received one single 0.5mL pilot scale dose of 13vPnC coadministered with DTaP-IPV-Hib at 3 and 4 months (infant series, dose 2 and 3).	Participants received one single 0.5mL manufacturing scale dose of 13vPnC coadministered with measles, mumps, and rubella vaccine (MMR) and 12 months of age (toddler dose).	Participants received one single 0.5mL pilot scale dose of 13vPnC coadministered with measles, mumps, and rubella vaccine (MMR) and 12 months of age (toddler dose).
Measure Participants	134	134	132	133	132	133	131	131
Tenderness-Any (n=133,130,128,128,124,119,115,117)	18.8 13.9%	20.0 14.9%	20.3 7.5%	17.2 NaN	15.3 NaN	12.6 NaN	24.3 NaN	29.1 NaN
Tenderness-Sig (n=131,129,128,128,124,119,112,114)	0.8 0.6%	3.9 2.9%	1.6 0.6%	3.1 NaN	1.6 NaN	0.0 NaN	1.8 NaN	3.5 NaN
Swelling-Any (n=132,130,129,129,126,122,113,115)	25.0 18.5%	20.0 14.9%	30.2 11.2%	27.1 NaN	29.4 NaN	30.3 NaN	22.1 NaN	26.1 NaN
Swelling-Mild (n=132,130,129,129,126,121,113,115)	22.7 16.8%	17.7 13.2%	29.5 11%	25.6 NaN	27.0 NaN	25.6 NaN	22.1 NaN	25.2 NaN
Swelling-Mod (n=132,129,128,128,124,120,113,114)	6.1 4.5%	7.0 5.2%	8.6 3.2%	8.6 NaN	8.9 NaN	13.3 NaN	8.8 NaN	8.8 NaN
Swelling-Severe(n=131,129,128,128,124,119,112,113)	0.0 0%	0.0 0%	0.0 0%	0.0 NaN	0.0 NaN	0.0 NaN	0.0 NaN	0.0 NaN
Redness-Any (n=132,131,129,131,125,123,115,116)	28.8 21.3%	24.4 18.2%	37.2 13.8%	33.6 NaN	40.0 NaN	34.1 NaN	37.4 NaN	42.2 NaN
Redness-Mild (n=132,131,129,131,125,123,115,115)	28.8 21.3%	22.9 17.1%	36.4 13.5%	33.6 NaN	38.4 NaN	33.3 NaN	33.9 NaN	36.5 NaN
Redness-Mod (n=131,129,128,128,124,119,113,114)	0.0 0%	1.6 1.2%	3.1 1.2%	1.6 NaN	5.6 NaN	3.4 NaN	10.6 NaN	12.3 NaN
Redness-Severe(n=131,129,128,128,124,119,112,113)	0.0 0%	0.0 0%	0.0 0%	0.0 NaN	0.0 NaN	0.0 NaN	0.0 NaN	0.9 NaN

3. Primary Outcome

Title	Percentage of Participants Reporting Pre-Specified Systemic Events (Infant Series)
Description	Systemic events (fever ≥ 38 degrees Celsius [C] but ≤ 39 C, fever >39 C but ≤ 40 C, fever > 40 C, decreased appetite, irritability, increased sleep, decreased sleep, use of medication (Meds)to prevent symptoms (sx), and use of medication to treat symptoms) were collected using an electronic diary. Participants may be represented in more than 1 category.
Time Frame	During the 4-day period after each dose

Outcome Measure Data

Analysis Population Description

The safety population included all participants (268) who received at least 1 dose of vaccine; (n) = number of participants reporting yes for at least 1 day or no for all days.

Arm/Group Title	13vPnC Manufacturing Dose 1	13vPnC Pilot Dose 1	13vPnC Manufacturing Dose 2	13vPnC Pilot Dose 2	13vPnC Manufacturing Dose 3	13vPnC Pilot Dose 3
Arm/Group Description	Participants received one single 0.5mL manufacturing scale dose of 13-valent pneumococcal conjugate vaccine (13vPnC) coadministered with combined diphtheria, tetanus, and acellular pertussis inactivated poliovirus, and hemophilus influenza type b vaccine (DTaP-IPV-Hib) and hepatitis B virus vaccine (HBV) at 2 months (infant series, dose 1).	Participants received one single 0.5mL pilot scale dose of 13-valent pneumococcal conjugate vaccine (13vPnC) coadministered with combined diphtheria, tetanus, and acellular pertussis inactivated poliovirus, and hemophilus influenza type b vaccine (DTaP-IPV-Hib) and hepatitis B virus vaccine (HBV) at 2 months (infant series, dose 1).	Participants received one single 0.5mL manufacturing scale dose of 13vPnC coadministered with DTaP-IPV-Hib at 3 and 4 months (infant series, dose 2 and 3).	Participants received one single 0.5mL pilot scale dose of 13vPnC coadministered with DTaP-IPV-Hib at 3 and 4 months (infant series, dose 2 and 3).	Participants received one single 0.5mL manufacturing scale dose of 13vPnC coadministered with DTaP-IPV-Hib at 3 and 4 months (infant series, dose 2 and 3).	Participants received one single 0.5mL pilot scale dose of 13vPnC coadministered with DTaP-IPV-Hib at 3 and 4 months (infant series, dose 2 and 3).
Measure Participants	134	134	132	133	132	133
Fever ≥38°C but ≤39°C (n=132,130,129,130,124,121)	18.2 13.5%	19.2 14.3%	16.3 6.1%	20.0 NaN	11.3 NaN	17.4 NaN
Fever >39°C but ≤40°C (n=131,129,128,128,124,119)	0.8 0.6%	0.8 0.6%	0.8 0.3%	1.6 NaN	0.0 NaN	3.4 NaN
Fever >40°C (n=131,129,128,128,124,119)	0.0 0%	0.0 0%	0.0 0%	0.0 NaN	0.0 NaN	0.0 NaN
Decreased appetite (n=133,129,129,128,125,121)	20.3 15%	24.0 17.9%	14.7 5.5%	15.6 NaN	16.8 NaN	19.0 NaN
Irritability (n=134,131,130,131,127,123)	50.0 37%	51.9 38.7%	53.8 20%	49.6 NaN	41.7 NaN	37.4 NaN
Increased sleep (n=132,129,128,129124,121)	41.7 30.9%	39.5 29.5%	25.0 9.3%	29.5 NaN	20.2 NaN	30.6 NaN
Decreased sleep (n=132,130,129,129,124,123)	27.3 20.2%	32.3 24.1%	24.0 8.9%	20.9 NaN	18.5 NaN	19.5 NaN
Meds to treat sx (n=132,130,128,128,124,123)	12.9 9.6%	17.7 13.2%	13.3 4.9%	14.1 NaN	8.9 NaN	14.6 NaN
Meds to prevent sx (n=132,130,128,129124,121)	12.9 9.6%	9.2 6.9%	11.7 4.3%	10.1 NaN	10.5 NaN	8.3 NaN

4. Primary Outcome

Title	Percentage of Participants Reporting Pre-Specified Systemic Events (Toddler Series)
Description	Systemic events (fever ≥ 38 degrees Celsius [C] but ≤ 39 C, fever >39 C but ≤ 40 C, fever > 40 C), decreased appetite, irritability, increased sleep, decreased sleep, use of medication to prevent symptoms, and use of medication to treat symptoms) were collected using an electronic diary. Participants may be represented in more than 1 category.
Time Frame	During the 4-day period after toddler dose

Outcome Measure Data

Analysis Population Description

The safety population included all participants who received at least 1 dose of vaccine; (n) = number of participants reporting yes for at least 1 day or no for all days.

Arm/Group Title	13vPnC Manufacturing	13vPnC Pilot
Arm/Group Description	Participants received one single 0.5mL manufacturing scale dose of 13vPnC coadministered with measles, mumps, and rubella vaccine (MMR) and 12 months of age (toddler dose).	Participants received one single 0.5mL pilot scale dose of 13vPnC coadministered with measles, mumps, and rubella vaccine (MMR) and 12 months of age (toddler dose).
Measure Participants	131	131
Fever ≥38°C but ≤39°C (n=114,114)	14.0 10.4%	13.2 9.9%
Fever >39°C but ≤40°C (n=112,113)	0.9 0.7%	0.9 0.7%
Fever >40°C (n=112,113)	0.0 0%	0.0 0%
Decreased appetite (n=115,117)	20.9 15.5%	23.1 17.2%
Irritability (n=119,123)	40.3 29.9%	44.7 33.4%
Increased sleep (n=114,119)	18.4 13.6%	16.8 12.5%
Decreased sleep (n=116,117)	13.8 10.2%	13.7 10.2%
Medication to treat symptoms (n=113,115)	17.7 13.1%	17.4 13%
Medication to prevent symptoms (n=114,114)	12.3 9.1%	12.3 9.2%

5. Primary Outcome

Title	Geometric Mean Antibody Concentration in 13vPnC Manufacturing Scale Group Relative to 13vPnC Pilot Scale Group After the 3-Dose Infant Series
Description	Antibody concentration/geometric mean concentration (GMC) as measured by enzyme-linked immunosorbent assay (ELISA) for 7 common pneumococcal serotypes (serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional pneumococcal serotypes specific to 13vPnC (Serotypes 1, 3, 5, 6A, 7F, and 19A) are presented.
Time Frame	One month after 3-dose infant series (5 months of age)

Outcome Measure Data

Analysis Population Description

Evaluable immunogenicity (per protocol) population were participants who adhered to the protocol requirements, had valid and determinate assay results, and had no other major protocol violations.

Arm/Group Title	13vPnC Manufacturing	13vPnC Pilot
Arm/Group Description	Participants received one single 0.5mL manufacturing scale dose of 13vPnC coadministered with Infanrix hexa at 2, 3, 4 months (infant series) and 12 months of age (toddler dose).	Participants received one single 0.5mL pilot scale dose of 13vPnC coadministered with Infanrix hexa at 2, 3, 4 months (infant series) and 12 months of age (toddler dose).
Measure Participants	128	131
Common Serotypes-Serotype 4	2.09	1.55
Common Serotypes - Serotype 6B	0.80	0.83
Common Serotypes - Serotype 9V	1.28	1.21
Common Serotypes - Serotype 14	2.15	2.30
Common Serotypes - Serotype 18C	1.60	1.51
Common Serotypes - Serotype 19F	1.60	1.64
Common Serotypes - Serotype 23F	0.82	0.92
Additional Serotypes - Serotype 1	1.42	1.29
Additional Serotypes - Serotype 3	1.20	1.21
Additional Serotypes - Serotype 5	0.96	1.00
Additional Serotypes - Serotype 6A	0.87	1.05
Additional Serotypes - Serotype 7F	2.00	2.14
Additional Serotypes - Serotype 19A	2.19	2.31

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 4 the GMC ratio was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.35
	Confidence Interval	() 95%; 1.10 to 1.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 6B the GMC ratio was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.96
	Confidence Interval	() 95%; 0.70 to 1.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 9V the GMC ratio was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.05
	Confidence Interval	() 95%; 0.89 to 1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 14 the GMC ratio was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.93
	Confidence Interval	() 95%; 0.71 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 18C the GMC ratio was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.06
	Confidence Interval	() 95%; 0.86 to 1.30
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 19F the GMC ratio was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.98
	Confidence Interval	() 95%; 0.81 to 1.17
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 23F the GMC ratio was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.90
	Confidence Interval	() 95%; 0.70 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 1 the GMC ratio was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.10
	Confidence Interval	() 95%; 0.88 to 1.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 3 the GMC ratio was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	1.00
	Confidence Interval	() 95%; 0.83 to 1.20
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 5 the GMC ratio was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.95
	Confidence Interval	() 95%; 0.79 to 1.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 6A the GMC ratio was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.83
	Confidence Interval	() 95%; 0.66 to 1.05
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 7F the GMC ratio was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.93
	Confidence Interval	() 95%; 0.79 to 1.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	13vPnC Manufacturing, 13vPnC Pilot
	Comments	For serotype 19A the GMC ratio was calculated
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.95
	Confidence Interval	() 95%; 0.79 to 1.13
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Arm/Group Title	13vPnC Manufacturing Infant Series		13vPnC Pilot Infant Series		13vPnC Manufacturing Post-Infant Series		13vPnC Pilot Post-Infant Series		13vPnC Manufacturing Toddler Series		13vPnC Pilot Toddler Series
Arm/Group Description	Participants received one single 0.5mL manufacturing scale dose of 13-valent pneumococcal conjugate vaccine (13vPnC) coadministered with combined diphtheria, tetanus, and acellular pertussis inactivated poliovirus, and hemophilus influenza type b vaccine (DTaP-IPV-Hib) and hepatitis B virus vaccine (HBV) at 2 months (infant series, dose 1). Participants received one single 0.5mL manufacturing scale dose of 13vPnC coadministered with DTaP-IPV-Hib at 3 and 4 months (infant series, dose 2 and 3).		Participants received one single 0.5mL pilot scale dose of 13-valent pneumococcal conjugate vaccine (13vPnC) coadministered with combined diphtheria, tetanus, and acellular pertussis inactivated poliovirus, and hemophilus influenza type b vaccine (DTaP-IPV-Hib) and hepatitis B virus vaccine (HBV) at 2 months (infant series, dose 1). Participants received one single 0.5mL pilot scale dose of 13vPnC coadministered with DTaP-IPV-Hib at 3 and 4 months (infant series, dose 2 and 3).		Participants received one single 0.5mL manufacturing scale dose of 13-valent pneumococcal conjugate vaccine (13vPnC) coadministered with combined diphtheria, tetanus, and acellular pertussis inactivated poliovirus, and hemophilus influenza type b vaccine (DTaP-IPV-Hib) and hepatitis B virus vaccine (HBV) at 2 months (infant series, dose 1). Participants received one single 0.5mL manufacturing scale dose of 13vPnC coadministered with DTaP-IPV-Hib at 3 and 4 months (infant series, dose 2 and 3). Assessment done at 5 months of age, 1 month after infant series.		Participants received one single 0.5mL pilot scale dose of 13-valent pneumococcal conjugate vaccine (13vPnC) coadministered with combined diphtheria, tetanus, and acellular pertussis inactivated poliovirus, and hemophilus influenza type b vaccine (DTaP-IPV-Hib) and hepatitis B virus vaccine (HBV) at 2 months (infant series, dose 1). Participants received one single 0.5mL pilot scale dose of 13vPnC coadministered with DTaP-IPV-Hib at 3 and 4 months (infant series, dose 2 and 3). Assessment done at 5 months of age, 1 month after infant series.		Participants received one single 0.5mL manufacturing scale dose of 13vPnC coadministered with measles, mumps, and rubella vaccine (MMR) and 12 months of age (toddler dose).		Participants received one single 0.5mL pilot scale dose of 13vPnC coadministered with measles, mumps, and rubella vaccine (MMR) and 12 months of age (toddler dose).
All Cause Mortality
	13vPnC Manufacturing Infant Series		13vPnC Pilot Infant Series		13vPnC Manufacturing Post-Infant Series		13vPnC Pilot Post-Infant Series		13vPnC Manufacturing Toddler Series		13vPnC Pilot Toddler Series
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	13vPnC Manufacturing Infant Series		13vPnC Pilot Infant Series		13vPnC Manufacturing Post-Infant Series		13vPnC Pilot Post-Infant Series		13vPnC Manufacturing Toddler Series		13vPnC Pilot Toddler Series
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/134 (3%)		2/134 (1.5%)		10/134 (7.5%)		11/134 (8.2%)		0/131 (0%)		1/131 (0.8%)
Eye disorders
Conjunctivitis	0/134 (0%)		0/134 (0%)		0/134 (0%)		1/134 (0.7%)		0/131 (0%)		0/131 (0%)
Gastrointestinal disorders
Diarrhoea	0/134 (0%)		1/134 (0.7%)		2/134 (1.5%)		1/134 (0.7%)		0/131 (0%)		0/131 (0%)
Gastroesophageal reflux disease	0/134 (0%)		0/134 (0%)		0/134 (0%)		1/134 (0.7%)		0/131 (0%)		0/131 (0%)
General disorders
Pyrexia	0/134 (0%)		0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Infections and infestations
Bronchitis	1/134 (0.7%)		0/134 (0%)		1/134 (0.7%)		2/134 (1.5%)		0/131 (0%)		0/131 (0%)
Bronchopneumonia	0/134 (0%)		0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Enterocolitis infectious	0/134 (0%)		0/134 (0%)		0/134 (0%)		1/134 (0.7%)		0/131 (0%)		0/131 (0%)
Gastroenteritis	0/134 (0%)		0/134 (0%)		3/134 (2.2%)		4/134 (3%)		0/131 (0%)		1/131 (0.8%)
Infectious mononucleosis	0/134 (0%)		0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Laryngitis	1/134 (0.7%)		0/134 (0%)		2/134 (1.5%)		1/134 (0.7%)		0/131 (0%)		0/131 (0%)
Nasopharyngitis	0/134 (0%)		0/134 (0%)		0/134 (0%)		1/134 (0.7%)		0/131 (0%)		0/131 (0%)
Otitis media	0/134 (0%)		0/134 (0%)		0/134 (0%)		1/134 (0.7%)		0/131 (0%)		0/131 (0%)
Pharyngitis	0/134 (0%)		0/134 (0%)		0/134 (0%)		1/134 (0.7%)		0/131 (0%)		0/131 (0%)
Pneumonia	1/134 (0.7%)		0/134 (0%)		2/134 (1.5%)		3/134 (2.2%)		0/131 (0%)		0/131 (0%)
Pneumonia primary atypical	0/134 (0%)		0/134 (0%)		0/134 (0%)		1/134 (0.7%)		0/131 (0%)		0/131 (0%)
Respiratory tract infection	1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Rotavirus infection	0/134 (0%)		0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Sepsis	1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Upper respiratory tract infection	0/134 (0%)		1/134 (0.7%)		1/134 (0.7%)		2/134 (1.5%)		0/131 (0%)		0/131 (0%)
Metabolism and nutrition disorders
Dehydration	0/134 (0%)		0/134 (0%)		0/134 (0%)		1/134 (0.7%)		0/131 (0%)		0/131 (0%)
Psychiatric disorders
Crying	0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	0/134 (0%)		0/134 (0%)		2/134 (1.5%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Bronchospasm	1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Other (Not Including Serious) Adverse Events
	13vPnC Manufacturing Infant Series		13vPnC Pilot Infant Series		13vPnC Manufacturing Post-Infant Series		13vPnC Pilot Post-Infant Series		13vPnC Manufacturing Toddler Series		13vPnC Pilot Toddler Series
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	70/134 (52.2%)		68/134 (50.7%)		3/134 (2.2%)		7/134 (5.2%)		48/131 (36.6%)		55/131 (42%)
Blood and lymphatic system disorders
Anaemia	2/134 (1.5%)		2/134 (1.5%)		0/134 (0%)		2/134 (1.5%)		0/131 (0%)		0/131 (0%)
Iron deficiency anaemia	0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Lymphadenitis	0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		1/131 (0.8%)
Congenital, familial and genetic disorders
Hip dysplasia	1/134 (0.7%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Atrial septal defect	0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Dacryostenosis congenital	1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Hydrocele	1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Plagiocephaly	1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Eye disorders
Conjunctivitis	5/134 (3.7%)		4/134 (3%)		0/134 (0%)		0/134 (0%)		1/131 (0.8%)		0/131 (0%)
Dacryostenosis acquired	0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Eyelid oedema	0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Gastrointestinal disorders
Diarrhoea	4/134 (3%)		3/134 (2.2%)		0/134 (0%)		0/134 (0%)		3/131 (2.3%)		1/131 (0.8%)
Dyspepsia	1/134 (0.7%)		4/134 (3%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Constipation	1/134 (0.7%)		2/134 (1.5%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Abdominal pain	1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Enlarged uvula	1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Frequent bowel movements	1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Infantile colic	1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Infrequent bowel movements	0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Teething	1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Gastrooesophageal reflux disease	0/134 (0%)		0/134 (0%)		1/134 (0.7%)		1/134 (0.7%)		0/131 (0%)		0/131 (0%)
Vomiting	0/134 (0%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		1/131 (0.8%)
General disorders
Pyrexia	2/134 (1.5%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		2/131 (1.5%)		0/131 (0%)
Irritability	0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Malaise	0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Fever ≥38°C but ≤39°C	24/132 (18.2%)		25/130 (19.2%)		0/134 (0%)		0/134 (0%)		16/114 (14%)		15/114 (13.2%)
Fever ≥38°C but ≤39°C	21/129 (16.3%)		26/130 (20%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Fever ≥38°C but ≤39°C	14/124 (11.3%)		21/121 (17.4%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Fever >39°C but ≤40°C	1/131 (0.8%)		1/129 (0.8%)		0/134 (0%)		0/134 (0%)		1/112 (0.9%)		1/113 (0.9%)
Fever >39°C but ≤40°C	1/128 (0.8%)		2/128 (1.6%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Fever >39°C but ≤40°C	0/124 (0%)		4/119 (3.4%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Fever >40°C	0/131 (0%)		0/129 (0%)		0/134 (0%)		0/134 (0%)		0/112 (0%)		0/113 (0%)
Fever >40°C	0/128 (0%)		0/128 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Fever >40°C	0/124 (0%)		0/119 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Decreased appetite	27/133 (20.3%)		31/129 (24%)		0/134 (0%)		0/134 (0%)		24/115 (20.9%)		27/117 (23.1%)
Decreased appetite	19/129 (14.7%)		20/128 (15.6%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Decreased appetite	21/125 (16.8%)		23/121 (19%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Irritability	67/134 (50%)		68/131 (51.9%)		0/134 (0%)		0/134 (0%)		48/119 (40.3%)		55/123 (44.7%)
Irritability	70/130 (53.8%)		65/131 (49.6%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Irritability	53/127 (41.7%)		46/123 (37.4%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Increased sleep	55/132 (41.7%)		51/129 (39.5%)		0/134 (0%)		0/134 (0%)		21/114 (18.4%)		20/119 (16.8%)
Increased sleep	32/128 (25%)		38/129 (29.5%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Increased sleep	25/124 (20.2%)		37/121 (30.6%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Decreased sleep	36/132 (27.3%)		42/130 (32.3%)		0/134 (0%)		0/134 (0%)		16/116 (13.8%)		16/117 (13.7%)
Decreased sleep	31/129 (24%)		27/129 (20.9%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Decreased sleep	23/124 (18.5%)		24/123 (19.5%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Immune system disorders
Food allergy	0/134 (0%)		0/134 (0%)		0/134 (0%)		1/134 (0.7%)		0/131 (0%)		0/131 (0%)
Milk allergy	0/134 (0%)		0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Infections and infestations
Rhinitis	12/134 (9%)		10/134 (7.5%)		0/134 (0%)		0/134 (0%)		1/131 (0.8%)		2/131 (1.5%)
Pharyngitis	9/134 (6.7%)		10/134 (7.5%)		0/134 (0%)		0/134 (0%)		5/131 (3.8%)		5/131 (3.8%)
Upper respiratory tract infection	8/134 (6%)		11/134 (8.2%)		0/134 (0%)		0/134 (0%)		2/131 (1.5%)		1/131 (0.8%)
Nasopharyngitis	8/134 (6%)		9/134 (6.7%)		0/134 (0%)		0/134 (0%)		1/131 (0.8%)		2/131 (1.5%)
Bronchitis	5/134 (3.7%)		7/134 (5.2%)		0/134 (0%)		0/134 (0%)		1/131 (0.8%)		2/131 (1.5%)
Candidiasis	2/134 (1.5%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Ear infection	2/134 (1.5%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Exanthema subitum	2/134 (1.5%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		1/131 (0.8%)
Viral infection	2/134 (1.5%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		1/131 (0.8%)		3/131 (2.3%)
Bronchopneumonia	1/134 (0.7%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Gastrointestinal infection	1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Lower respiratory tract infection	1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Oral candidiasis	0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Tonsillitis	1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Gastroenteritis	0/134 (0%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		2/131 (1.5%)		2/131 (1.5%)
Laryngitis	0/134 (0%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		2/131 (1.5%)		0/131 (0%)
Urinary tract infection	0/134 (0%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		1/131 (0.8%)		1/131 (0.8%)
Otitis media acute	0/134 (0%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		1/131 (0.8%)
Respiratory tract infection	0/134 (0%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		1/131 (0.8%)		0/131 (0%)
Injury, poisoning and procedural complications
Corneal abrasion	1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Musculoskeletal and connective tissue disorders
Rickets	1/134 (0.7%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Posture abnormal	1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Nervous system disorders
Hypertonia	0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Hypotonia	0/134 (0%)		0/134 (0%)		0/134 (0%)		1/134 (0.7%)		0/131 (0%)		0/131 (0%)
Poor quality sleep	0/134 (0%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		1/131 (0.8%)
Psychiatric disorders
Crying	0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Psychomotor retardation	0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Reproductive system and breast disorders
Posthitis	0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea	2/134 (1.5%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Asthma	0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Cough	0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		1/131 (0.8%)
Dysphonia	0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Skin and subcutaneous tissue disorders
Rash	2/134 (1.5%)		2/134 (1.5%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Dermatitis atopic	1/134 (0.7%)		2/134 (1.5%)		1/134 (0.7%)		0/134 (0%)		1/131 (0.8%)		1/131 (0.8%)
Dermatitis	1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		1/131 (0.8%)
Eczema	0/134 (0%)		1/134 (0.7%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Dermatitis allergic	0/134 (0%)		0/134 (0%)		0/134 (0%)		2/134 (1.5%)		1/131 (0.8%)		0/131 (0%)
Tenderness (Any)	25/133 (18.8%)		26/130 (20%)		0/134 (0%)		0/134 (0%)		28/115 (24.3%)		34/117 (29.1%)
Tenderness (Any)	26/128 (20.3%)		22/128 (17.2%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Tenderness (Any)	19/124 (15.3%)		15/119 (12.6%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Tenderness (Significant)	1/131 (0.8%)		5/129 (3.9%)		0/134 (0%)		0/134 (0%)		2/112 (1.8%)		4/114 (3.5%)
Tenderness (Significant)	2/128 (1.6%)		4/128 (3.1%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Tenderness (Significant)	2/124 (1.6%)		0/119 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Induration (Any)	33/132 (25%)		26/130 (20%)		0/134 (0%)		0/134 (0%)		25/113 (22.1%)		30/115 (26.1%)
Induration (Any)	39/129 (30.2%)		35/129 (27.1%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Induration (Any)	37/126 (29.4%)		37/122 (30.3%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Induration (Mild)	30/132 (22.7%)		23/130 (17.7%)		0/134 (0%)		0/134 (0%)		25/113 (22.1%)		29/115 (25.2%)
Induration (Mild)	38/129 (29.5%)		33/129 (25.6%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Induration(Mild)	34/126 (27%)		31/121 (25.6%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Induration (Moderate)	8/132 (6.1%)		9/129 (7%)		0/134 (0%)		0/134 (0%)		10/113 (8.8%)		10/114 (8.8%)
Induration (Moderate)	11/128 (8.6%)		11/128 (8.6%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Induration (Moderate)	11/124 (8.9%)		16/120 (13.3%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Induration (Severe)	0/131 (0%)		0/129 (0%)		0/134 (0%)		0/134 (0%)		0/112 (0%)		0/113 (0%)
Induration (Severe)	0/128 (0%)		0/128 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Induration (Severe)	0/124 (0%)		0/119 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Erythema (Any)	38/132 (28.8%)		32/131 (24.4%)		0/134 (0%)		0/134 (0%)		43/115 (37.4%)		49/116 (42.2%)
Erythema (Any)	48/129 (37.2%)		44/131 (33.6%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Erythema (Any)	50/125 (40%)		42/123 (34.1%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Erythema (Mild)	38/132 (28.8%)		30/131 (22.9%)		0/134 (0%)		0/134 (0%)		39/115 (33.9%)		42/115 (36.5%)
Erythema (Mild)	47/129 (36.4%)		44/131 (33.6%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Erythema (Mild)	48/125 (38.4%)		41/123 (33.3%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Erythema (Moderate)	0/131 (0%)		2/129 (1.6%)		0/134 (0%)		0/134 (0%)		12/113 (10.6%)		14/114 (12.3%)
Erythema (Moderate)	4/128 (3.1%)		2/128 (1.6%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Erythema (Moderate)	7/124 (5.6%)		4/119 (3.4%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Erythema (Severe)	0/131 (0%)		0/129 (0%)		0/134 (0%)		0/134 (0%)		0/112 (0%)		1/113 (0.9%)
Erythema (Severe)	0/128 (0%)		0/128 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)
Erythema (Severe)	0/124 (0%)		0/119 (0%)		0/134 (0%)		0/134 (0%)		0/131 (0%)		0/131 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The PIs agreed to allow the sponsor 60 days to review and require changes to presentations or publications but only to protect confidential information and intellectual property, and for the sponsor to file a patent application, as applicable. The PIs also agreed for data to be presented first as a joint, multi-center publication.