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Clinical Trial Results:
A Phase III Randomized, Double-Blind, Active-Comparator Controlled Clinical Trial to Study the Safety, Tolerability, and Immunogenicity of V419 in Healthy Infants When Given at 2, 3, 4, and 12 Months (V419-007-03)

Summary
EudraCT number	2010-021490-37
Trial protocol	BE FI DE
Global end of trial date	03 Mar 2013

Results information
Results version number	v2(current)
This version publication date	15 Nov 2019
First version publication date	02 Aug 2015
Other versions	v1
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

V419-007

ISRCTN number

US NCT number

NCT01341639

WHO universal trial number (UTN)

Sponsor organisation name

Merck Sharp & Dohme Corp.

Sponsor organisation address

2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033

Public contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com

Scientific contact

Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com

Is trial part of an agreed paediatric investigation plan (PIP)

Yes

EMA paediatric investigation plan number(s)

EMEA-000394-PIP01-08

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

03 Mar 2013

Is this the analysis of the primary completion data?

Yes

Primary completion date

03 Mar 2013

Global end of trial reached?

Yes

Global end of trial date

03 Mar 2013

Was the trial ended prematurely?

Main objective of the trial

This study determined whether participants who receive the vaccine V419 at 2, 3, 4, and 12 months of age have an acceptable immune response to the vaccine. The study also determined whether the immune response to V419 is similar to that of participants who receive a licensed vaccine control.

Protection of trial subjects

This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.

Background therapy

Evidence for comparator

Actual start date of recruitment

26 May 2011

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 94

Country: Number of subjects enrolled

Finland: 892

Country: Number of subjects enrolled

Germany: 264

Worldwide total number of subjects

1250

EEA total number of subjects

1250

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

1250

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Healthy infants 46 to 74 days old were enrolled in this study.

Period 1 title

Infant Series

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

PR5I

Arm description

The PR5I group received V419, Prevenar 13™, and RotaTeq™ at 2, 3, and 4 months; followed by V419 and ProQuad™ at 12 months, and Prevenar 13™ and ProQuad™ at 13 months.

Arm type

Experimental

Investigational medicinal product name

V419

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

V419 (Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus, Haemophilus b Conjugate [MeningococcalOuter Membrane Protein Complex], and Hepatitis B [Recombinant] Vaccine) 0.5 mL intramuscular injection at 2, 3, 4, and 12 months of age.

Investigational medicinal product name

Prevenar 13

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Prevenar 13 0.5 mL intramuscular injection at 2, 3, 4,and 13 months of age

Investigational medicinal product name

RotaTeq

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

RotaTeq (pentavalent combination live vaccine of 5 human-bovine reassortant rotavirus strains) 2 mL oral dose at 2, 3, and 4 months of age

Investigational medicinal product name

ProQuad™

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

ProQuad™ 0.5 mL subcutaneous injection at 12 and 13 months of age

INFANRIX™ hexa

Arm description

The INFANRIX™ hexa group received INFANRIX™ hexa, Prevenar 13™, and RotaTeq™ at 2, 3, and 4 months; followed by INFANRIX™ hexa and ProQuad™ at 12 months; and Prevenar 13™ and ProQuad™ at 13 months.

Arm type

Active comparator

Investigational medicinal product name

INFANRIX™ hexa

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

INFANRIX™ hexa 0.5 mL intramuscular injection at 2, 3, 4, and 12 months of age.

Investigational medicinal product name

ProQuad™

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

ProQuad™ 0.5 mL subcutaneous injection at 12 and 13 months of age

Investigational medicinal product name

RotaTeq

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

RotaTeq (pentavalent combination live vaccine of 5 human-bovine reassortant rotavirus strains) 2 mL oral dose at 2, 3, and 4 months of age

Number of subjects in period 1	PR5I	INFANRIX™ hexa
Started	628	622
Site 0048 Excluded	611	606
Treated	610	605
Completed	599	590
Not completed	29	32
Consent withdrawn by subject	11	8
Not Vaccinated	-	1
Adverse event, non-fatal	-	5
Site 0048 Participants	17	16
Lost to follow-up	-	2
Protocol deviation	1	-

Period 2 title

Interim Period

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

PR5I

Arm description

The PR5I group received V419, Prevenar 13™, and RotaTeq™ at 2, 3, and 4 months; followed by V419 and ProQuad™ at 12 months, and Prevenar 13™ and ProQuad™ at 13 months.

Arm type

Experimental

Investigational medicinal product name

V419

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Investigational medicinal product name

Prevenar 13

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Prevenar 13 0.5 mL intramuscular injection at 2, 3, 4,and 13 months of age

Investigational medicinal product name

RotaTeq

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

RotaTeq (pentavalent combination live vaccine of 5 human-bovine reassortant rotavirus strains) 2 mL oral dose at 2, 3, and 4 months of age

Investigational medicinal product name

ProQuad™

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

ProQuad™ 0.5 mL subcutaneous injection at 12 and 13 months of age

INFANRIX™ hexa

Arm description

Arm type

Active comparator

Investigational medicinal product name

INFANRIX™ hexa

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

INFANRIX™ hexa 0.5 mL intramuscular injection at 2, 3, 4, and 12 months of age.

Investigational medicinal product name

ProQuad™

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

ProQuad™ 0.5 mL subcutaneous injection at 12 and 13 months of age

Investigational medicinal product name

RotaTeq

Investigational medicinal product code

Other name

Pharmaceutical forms

Oral solution

Routes of administration

Oral use

Dosage and administration details

RotaTeq (pentavalent combination live vaccine of 5 human-bovine reassortant rotavirus strains) 2 mL oral dose at 2, 3, and 4 months of age

Number of subjects in period 2	PR5I	INFANRIX™ hexa
Started	599	590
Completed	591	581
Not completed	8	9
Consent withdrawn by subject	6	7
Physician decision	-	1
Lost to follow-up	2	-
Protocol deviation	-	1

Period 3 title

Toddler Dose

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

PR5I

Arm description

The PR5I group received V419, Prevenar 13™, and RotaTeq™ at 2, 3, and 4 months; followed by V419 and ProQuad™ at 12 months, and Prevenar 13™ and ProQuad™ at 13 months.

Arm type

Experimental

Investigational medicinal product name

V419

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Investigational medicinal product name

Prevenar 13

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Prevenar 13 0.5 mL intramuscular injection at 2, 3, 4,and 13 months of age

Investigational medicinal product name

RotaTeq

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder, Injection

Routes of administration

Intramuscular use

Dosage and administration details

RotaTeq (pentavalent combination live vaccine of 5 human-bovine reassortant rotavirus strains) 2 mL oral dose at 2, 3, and 4 months of age

Investigational medicinal product name

ProQuad™

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

ProQuad™ 0.5 mL subcutaneous injection at 12 and 13 months of age

INFANRIX™ hexa

Arm description

Arm type

Active comparator

Investigational medicinal product name

INFANRIX™ hexa

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

INFANRIX™ hexa 0.5 mL intramuscular injection at 2, 3, 4, and 12 months of age.

Investigational medicinal product name

RotaTeq

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder, Injection

Routes of administration

Intramuscular use

Dosage and administration details

RotaTeq (pentavalent combination live vaccine of 5 human-bovine reassortant rotavirus strains) 2 mL oral dose at 2, 3, and 4 months of age

Investigational medicinal product name

ProQuad™

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

ProQuad™ 0.5 mL subcutaneous injection at 12 and 13 months of age

Number of subjects in period 3	PR5I	INFANRIX™ hexa
Started	590	582
Completed	539	548
Not completed	51	35
Transferred to other arm/group	1	-
Did not receive ProQuad	50	35
Joined	0	1
Transferred in from other group/arm	-	1

Period 4 title

Post-Treatment

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

PR5I

Arm description

The PR5I group received V419, Prevenar 13™, and RotaTeq™ at 2, 3, and 4 months; followed by V419 and ProQuad™ at 12 months, and Prevenar 13™ and ProQuad™ at 13 months.

Arm type

Experimental

Investigational medicinal product name

V419

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Investigational medicinal product name

Prevenar 13

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

Prevenar 13 0.5 mL intramuscular injection at 2, 3, 4,and 13 months of age

Investigational medicinal product name

RotaTeq

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder, Injection

Routes of administration

Intramuscular use

Dosage and administration details

RotaTeq (pentavalent combination live vaccine of 5 human-bovine reassortant rotavirus strains) 2 mL oral dose at 2, 3, and 4 months of age

Investigational medicinal product name

ProQuad™

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

ProQuad™ 0.5 mL subcutaneous injection at 12 and 13 months of age

INFANRIX™ hexa

Arm description

Arm type

Active comparator

Investigational medicinal product name

INFANRIX™ hexa

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Intramuscular use

Dosage and administration details

INFANRIX™ hexa 0.5 mL intramuscular injection at 2, 3, 4, and 12 months of age.

Investigational medicinal product name

RotaTeq

Investigational medicinal product code

Other name

Pharmaceutical forms

Inhalation powder, Injection

Routes of administration

Intramuscular use

Dosage and administration details

RotaTeq (pentavalent combination live vaccine of 5 human-bovine reassortant rotavirus strains) 2 mL oral dose at 2, 3, and 4 months of age

Investigational medicinal product name

ProQuad™

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

ProQuad™ 0.5 mL subcutaneous injection at 12 and 13 months of age

Number of subjects in period 4	PR5I	INFANRIX™ hexa
Started	539	548
Completed	539	545
Not completed	0	3
Consent withdrawn by subject	-	1
Adverse event, non-fatal	-	2

Baseline characteristics

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Subject analysis set title

PR5I

Subject analysis set type

Per protocol

Subject analysis set description

The PR5I group received V419, Prevenar 13™, and RotaTeq™ at 2, 3, and 4 months; followed by V419 and ProQuad™ at 12 months, and Prevenar 13™ and ProQuad™ at 13 months. All randomized participants excluding participants from site 0048.

Subject analysis set title

INFANRIX™ hexa

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis sets values	PR5I	INFANRIX™ hexa
Number of subjects	611	606
Age Categorical
Units: Subjects
In utero	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0
Newborns (0-27 days)	0	0
Infants and toddlers (28 days-23 months)	611	606
Children (2-11 years)	0	0
Adolescents (12-17 years)	0	0
Adults (18-64 years)	0	0
From 65-84 years	0	0
85 years and over	0	0
Age Continuous
Units:
	62 ( 46 )	62 ( 46 )
Gender Categorical
Units: Subjects
Female	291	290
Male	320	316
Age Continuous
Units: Days
arithmetic mean (standard deviation)	61.4 ( 6.9 )	61.5 ( 6.9 )

End points

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Reporting group title

PR5I

Reporting group description

The PR5I group received V419, Prevenar 13™, and RotaTeq™ at 2, 3, and 4 months; followed by V419 and ProQuad™ at 12 months, and Prevenar 13™ and ProQuad™ at 13 months.

Reporting group title

INFANRIX™ hexa

Reporting group description

Reporting group title

PR5I

Reporting group description

The PR5I group received V419, Prevenar 13™, and RotaTeq™ at 2, 3, and 4 months; followed by V419 and ProQuad™ at 12 months, and Prevenar 13™ and ProQuad™ at 13 months.

Reporting group title

INFANRIX™ hexa

Reporting group description

Reporting group title

PR5I

Reporting group description

The PR5I group received V419, Prevenar 13™, and RotaTeq™ at 2, 3, and 4 months; followed by V419 and ProQuad™ at 12 months, and Prevenar 13™ and ProQuad™ at 13 months.

Reporting group title

INFANRIX™ hexa

Reporting group description

Reporting group title

PR5I

Reporting group description

The PR5I group received V419, Prevenar 13™, and RotaTeq™ at 2, 3, and 4 months; followed by V419 and ProQuad™ at 12 months, and Prevenar 13™ and ProQuad™ at 13 months.

Reporting group title

INFANRIX™ hexa

Reporting group description

Subject analysis set title

PR5I

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

INFANRIX™ hexa

Subject analysis set type

Per protocol

Subject analysis set description

Primary: Percentage of participants vaccinated with PR5I with acceptable antibody (Ab) response to Haemophilus influenzae type b, diphtheria, tetanus, and poliovirus types 1, 2 & 3, at 5 months

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End point title

Percentage of participants vaccinated with PR5I with acceptable antibody (Ab) response to Haemophilus influenzae type b, diphtheria, tetanus, and poliovirus types 1, 2 & 3, at 5 months ^[1]

End point description

Antibody titres in the PR5I group were measured by Radioimmunoassay (RIA) for Haemophilus influenzae type b (PRP), Micrometabolic inhibition test (MIT) for diphtheria & poliovirus, and Enzyme-Linked Immunosorbent Assay (ELISA) for tetanus. 95% confidence interval (CI) were calculated based on the exact binomial method by Clopper and Pearson. The immune response to PR5I vaccine was considered as acceptable if the lower bounds of the 2-sided 95% CI for the response rates were greater than the predetermined lower CI limits for PRP, diphtheria (80%), tetanus (90%), and IPV1, 2 & 3 (90%). The population analyzed was all participants in the PR5I group who met inclusion criteria, were not protocol violators, received vaccinations within acceptable day ranges, and who had serology results within revised windows (RW) of Days 28 to 51 Post-Dose 3. Participants from site 0048 were excluded.

End point type

Primary

End point timeframe

One month after post-dose 3 of PRI5 (5 months old)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical comparisons between treatment groups were neither planned nor performed for this primary endpoint.

End point values	PR5I
Number of subjects analysed	550
Units: Percentage of participants
number (confidence interval 95%)
Anti-PRP ≥0.15 μg/mL (n=550)	98.36 (96.92 to 99.25)
Anti-Diphtheria ≥0.01 IU/mL (n=542)	99.82 (98.98 to 100)
Anti-Tetanus ≥0.01 IU/mL (n=538)	100 (99.32 to 100)
Anti-IPV1 ≥8 (1/dil) (n=547)	100 (99.33 to 100)
Anti-IPV2 ≥8 (1/dil) (n=547)	99.82 (98.99 to 100)
Anti-IPV3 ≥8 (1/dil) (n=545)	100 (99.33 to 100)

No statistical analyses for this end point

Primary: Percentage of participants vaccinated with PR5I with acceptable Ab response or seroresponse rates to all antigens contained in the PR5I vaccine one month after the toddler dose at 13 months

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End point title

Percentage of participants vaccinated with PR5I with acceptable Ab response or seroresponse rates to all antigens contained in the PR5I vaccine one month after the toddler dose at 13 months ^[2]

End point description

Antibody titres in the PR5I group were measured by RIA for PRP, MIT for diphtheria & poliovirus, enhanced Chemiluminescence assay (ECi)) for Hepatitis B surface antigen (HBsAg) and ELISA for tetanus, Pertussis toxoid (PT), Filamentous haemagglutinin (FHA), Fimbriae types 2 & 3 (FIM) & Pertactin (PRN). 95% confidence interval (CI) were calculated based on the exact binomial method by Clopper and Pearson. The immune response to PR5I vaccine was considered as acceptable if the lower bounds of the 2-sided 95% CI for the response rates were greater than the lower CI limits for PRP, PT, FHA, FIM, and PRN (75%); Diphtheria (80%); HBsAG, IPV 1, 2, 3 (90%). The population analyzed was all participants in the PR5I group who met inclusion criteria, were not protocol violators, received vaccinations within acceptable day ranges, and who had serology results within RW of Days 28 to 51 Post-Toddler dose. Participants from site 0048 were excluded.

End point type

Primary

End point timeframe

One month after toddler dose of PRI5 (13 months old)

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Statistical comparisons between treatment groups were neither planned nor performed for this primary endpoint.

End point values	PR5I
Number of subjects analysed	551
Units: Percentage of participants
number (confidence interval 95%)
Anti-PRP ≥1.0 μg/mL (n=439)	94.99 (92.51 to 96.83)
Anti-Diphtheria ≥0.1 IU/mL (n=531)	99.81 (98.96 to 100)
Anti-Tetanus ≥0.1 IU/mL (n=528)	100 (99.30 to 100)
Anti-IPV1 ≥8 (1/dil) (n=538)	99.81 (98.97 to 100)
Anti-IPV2 ≥8 (1/dil) (n=538)	100 (99.32 to 100)
Anti-IPV3 ≥8 (1/dil) (n=541)	100 (99.32 to 100)
Anti-HBsAg ≥10 mIU/mL(n=551)	99.64 (98.70 to 99.96)
Anti-PT seroresponse (n=543)	99.82 (98.98 to 100)
Anti-FHA seroresponse (n=542)	97.23 (95.48 to 98.44)
Anti-FIM seroresponse (n=508)	99.61 (98.59 to 99.95)
Anti-PRN seroresponse (n=543)	98.90 (97.61 to 99.59)

No statistical analyses for this end point

Primary: Percentage of participants vaccinated with PR5I compared with INFANRIX™ hexa with acceptable Ab response to Haemophilus influenzae type b, diphtheria, tetanus, and poliovirus types 1, 2 & 3, at 5 months

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End point title

Percentage of participants vaccinated with PR5I compared with INFANRIX™ hexa with acceptable Ab response to Haemophilus influenzae type b, diphtheria, tetanus, and poliovirus types 1, 2 & 3, at 5 months

End point description

Antibody titres were measured by RIA for PRP, MIT for diphtheria & poliovirus, and ELISA for tetanus. Percentage of participants with an Ab titre ≥0.15 μg/mL for Hib) (PRP); ≥0.01 IU/mL; for diphtheria & tetanus; ≥8 (1/dil) for inactivated poliovirus types 1, 2 & 3 (IPV1, 2 & 3) are reported. The estimated response rates are based on the method by Miettinen and Nurminen stratified by country. The population analyzed was all participants who met inclusion criteria, were not protocol violators, received vaccinations within acceptable day ranges, and who had serology results within RW of Days 28 to 51 Post-Dose 3. Participants from site 0048 were excluded.

End point type

Primary

End point timeframe

One month after post-dose 3 of PRI5 (5 months old)

End point values	PR5I	INFANRIX™ hexa
Number of subjects analysed	550	530
Units: Percentage of participants
number (not applicable)
Anti-PRP ≥0.15 μg/mL (n=550,521)	98.36	86.99
Anti-Diphtheria ≥0.01 IU/mL (n=542,517)	99.81	99.81
Anti-Tetanus ≥0.01 IU/mL (n=538,519)	100	100
Anti-IPV1 ≥8 (1/dil) (n=547,528)	100	99.81
Anti-IPV2 ≥8 (1/dil) (n=547,530)	99.82	99.62
Anti-IPV3 ≥8 (1/dil) (n=545,525)	100	100

Difference in percentages: PRP

Statistical analysis description

PR5I minus INFANRIX™ hexa

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1080

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[3]

P-value

< 0.001 ^[4]

Method

Miettinen & Nurminen

Parameter type

Difference in percentages

Point estimate

11.37

Confidence interval

level

95%

sides

2-sided

lower limit

8.44

upper limit

14.68

Notes
[3] - If the lower bound of the 95% CI was greater than -10% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
[4] - 1-sided

Difference in percentages: Diphtheria

Statistical analysis description

PR5I minus INFANRIX™ hexa

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1080

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[5]

P-value

< 0.001 ^[6]

Method

Miettinen & Nurminen

Parameter type

Difference in percentages

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.95

upper limit

0.96

Notes
[5] - If the lower bound of the 95% CI was greater than -10% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate
[6] - 1-sided

Difference in percentages: Tetanus

Statistical analysis description

PR5I minus INFANRIX™ hexa

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1080

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[7]

P-value

< 0.001 ^[8]

Method

Miettinen & Nurminen

Parameter type

Difference in percentages

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.71

upper limit

0.74

Notes
[7] - If the lower bound of the 95% CI was greater than -5% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
[8] - 1-sided

Difference in percentages: IPV1

Statistical analysis description

PR5I minus INFANRIX™ hexa

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1080

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[9]

P-value

< 0.001 ^[10]

Method

Miettinen & Nurminen

Parameter type

Difference in percentages

Point estimate

0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.51

upper limit

1.07

Notes
[9] - If the lower bound of the 95% CI was greater than -5% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
[10] - 1-sided

Difference in percentages: IPV2

Statistical analysis description

PR5I minus INFANRIX™ hexa

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1080

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[11]

P-value

< 0.001 ^[12]

Method

Miettinen & Nurminen

Parameter type

Difference in percentages

Point estimate

0.19

Confidence interval

level

95%

sides

2-sided

lower limit

-0.69

upper limit

1.21

Notes
[11] - If the lower bound of the 95% CI was greater than -5% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
[12] - 1-sided

Difference in percentages: IPV3

Statistical analysis description

PR5I minus INFANRIX™ hexa

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1080

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[13]

P-value

< 0.001 ^[14]

Method

Miettinen & Nurminen

Parameter type

Difference in percentages

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.7

upper limit

0.73

Notes
[13] - If the lower bound of the 95% CI was greater than -5% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
[14] - 1-sided

Primary: Percentage of participants vaccinated with PR5I compared with INFANRIX™ hexa with acceptable Ab response rates to Hepatitis B and seroresponse to Pertussis antigens Pt, FHA and PRN one month after the toddler dose at 13 months old

Top of page

End point title

Percentage of participants vaccinated with PR5I compared with INFANRIX™ hexa with acceptable Ab response rates to Hepatitis B and seroresponse to Pertussis antigens Pt, FHA and PRN one month after the toddler dose at 13 months old

End point description

Antibody titres were measured by ECi for HBsAg and ELISA for PT, FHA, & PRN. Percentage of participants with an Ab titre ≥10 mIU/mL HBsAg; ≥8 (1/dil) for IPV1, 2 & 3, and seroresponse to PT, FHA, and PRN are reported. The estimated response rates are based on the method by Miettinen and Nurminen stratified by country. The population analyzed was all participants who met inclusion criteria, were not protocol violators, received vaccinations within acceptable day ranges, and who had serology results within RW of Days 28 to 51 Post-Toddler dose. Participants from site 0048 were excluded.

End point type

Primary

End point timeframe

One month after toddler dose of PRI5 (13 months old)

End point values	PR5I	INFANRIX™ hexa
Number of subjects analysed	551	531
Units: Percentage of participants
number (not applicable)
Anti-HBsAg ≥10 mIU/mL (n=551, 531)	99.64	99.06
Anti-PT seroresponse (n=543, 523)	99.82	98.49
Anti-FHA seroresponse (n=542, 524)	97.22	99.81
Anti-PRN seroresponse (n=543, 523)	98.89	98.86

Difference in percentages: HBsAg

Statistical analysis description

PR5I minus INFANRIX™ hexa

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1082

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[15]

P-value

< 0.001 ^[16]

Method

Miettinen & Nurminen

Parameter type

Difference in percentages

Point estimate

0.58

Confidence interval

level

95%

sides

2-sided

lower limit

-0.49

upper limit

1.85

Notes
[15] - If the lower bound of the 95% CI was greater than -10% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
[16] - 1-sided

Difference in percentages: PT

Statistical analysis description

PR5I minus INFANRIX™ hexa

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1082

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[17]

P-value

< 0.001 ^[18]

Method

Miettinen & Nurminen

Parameter type

Difference in percentages

Point estimate

1.33

Confidence interval

level

95%

sides

2-sided

lower limit

0.32

upper limit

2.86

Notes
[17] - If the lower bound of the 95% CI was greater than -10% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
[18] - 1-sided

Difference in percentages: FHA

Statistical analysis description

PR5I minus INFANRIX™ hexa

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1082

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[19]

P-value

< 0.001 ^[20]

Method

Miettinen & Nurminen

Parameter type

Difference in percentages

Point estimate

-2.59

Confidence interval

level

95%

sides

2-sided

lower limit

-4.39

upper limit

-1.29

Notes
[19] - If the lower bound of the 95% CI was greater than -10% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
[20] - 1-sided

Difference in percentages: PRN

Statistical analysis description

PR5I minus INFANRIX™ hexa

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1082

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[21]

P-value

< 0.001 ^[22]

Method

Miettinen & Nurminen

Parameter type

Difference in percentages

Point estimate

0.03

Confidence interval

level

95%

sides

2-sided

lower limit

-1.4

upper limit

1.52

Notes
[21] - If the lower bound of the 95% CI was greater than -10% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
[22] - 1-sided

Secondary: Percentage of participants vaccinated with PR5I with acceptable Ab response to measles, mumps, rubella and varicella one month after the toddler dose of ProQuad at 13 months old

Top of page

End point title

Percentage of participants vaccinated with PR5I with acceptable Ab response to measles, mumps, rubella and varicella one month after the toddler dose of ProQuad at 13 months old

End point description

Ab titres were measured by ELISA, excepting the Ab to varicella which was determined by glycoprotein ELISA. Percentage of participants with an Ab titre ≥255 mIU/mL for measles, ≥10 Ab units/mL for mumps, ≥10 IU/mL for rubella, and ≥5 gpELISA units/mL for varicella are reported. 95% CI were calculated based on the exact binomial method by Clopper and Pearson. The immune response to ProQuad vaccine was considered as acceptable if the lower bounds of the 2-sided 95% CI for the response rates were greater than the predetermined lower CI limits: 90% for measles, mumps & rubella, and 76% for varicella. The population analyzed was all participants in the PR5I group who met inclusion criteria, were not protocol violators, received vaccinations within acceptable day ranges, and who had serology results within RW of Days 28 to 51 Post-Toddler dose. Participants from site 0048 were excluded. Participants in the INFANRIX™ hexa group were not analyzed for this outcome measure.

End point type

Secondary

End point timeframe

One month after toddler dose of PRI5 (13 months old)

End point values	PR5I
Number of subjects analysed	467
Units: Percentage of participants
number (confidence interval 95%)
Anti-Measles ≥255 mIU/mL	96.15 (93.98 to 97.70)
Anti-Mumps ≥10 Ab units/mL	94.86 (92.45 to 96.68)
Anti-Rubella ≥10 IU/mL	98.29 (96.65 to 99.26)
Anti-Varicella ≥5 gpELISA units/mL	97.64 (95.82 to 98.82)

No statistical analyses for this end point

Secondary: Percentage of participants vaccinated with PR5I compared with INFANRIX™ hexa with acceptable Ab response to measles, mumps, rubella and varicella one month after the toddler dose of ProQuad at 13 months old

Top of page

End point title

Percentage of participants vaccinated with PR5I compared with INFANRIX™ hexa with acceptable Ab response to measles, mumps, rubella and varicella one month after the toddler dose of ProQuad at 13 months old

End point description

End point type

Secondary

End point timeframe

One month after toddler dose of PRI5 (13 months old)

End point values	PR5I	INFANRIX™ hexa
Number of subjects analysed	467	474
Units: Percentage of participants
number (not applicable)
Anti-Measles ≥255 mIU/mL	96.15	96.41
Anti-Mumps ≥10 Ab units/mL	94.86	91.78
Anti-Rubella ≥10 IU/mL	98.28	97.89
Anti-Varicella ≥5 gpELISA units/mL	97.64	97.66

Difference in percentages: Measles

Statistical analysis description

PR5I minus INFANRIX™ hexa

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

941

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[23]

P-value

< 0.001 ^[24]

Method

Miettinen & Nurminen

Parameter type

Difference in percentages

Point estimate

-0.26

Confidence interval

level

95%

sides

2-sided

lower limit

-2.82

upper limit

2.25

Notes
[23] - If the lower bound of the 95% CI was greater than -5% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
[24] - 1-sided

Difference in percentages: Mumps

Statistical analysis description

PR5I minus INFANRIX™ hexa

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

941

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[25]

P-value

< 0.001 ^[26]

Method

Miettinen & Nurminen

Parameter type

Difference in percentages

Point estimate

3.07

Confidence interval

level

95%

sides

2-sided

lower limit

-0.12

upper limit

6.4

Notes
[25] - If the lower bound of the 95% CI was greater than -5% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
[26] - 1-sided

Difference in percentages: Rubella

Statistical analysis description

PR5I minus INFANRIX™ hexa

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

941

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[27]

P-value

< 0.001 ^[28]

Method

Miettinen & Nurminen

Parameter type

Difference in percentages

Point estimate

0.39

Confidence interval

level

95%

sides

2-sided

lower limit

-1.5

upper limit

2.34

Notes
[27] - If the lower bound of the 95% CI was greater than -5% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
[28] - 1-sided

Difference in percentages: Varicella

Statistical analysis description

PR5I minus INFANRIX™ hexa

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

941

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[29]

P-value

< 0.001 ^[30]

Method

Miettinen & Nurminen

Parameter type

Difference in percentages

Point estimate

-0.02

Confidence interval

level

95%

sides

2-sided

lower limit

-2.11

upper limit

2.06

Notes
[29] - If the lower bound of the 95% CI was greater than -10% (non-inferiority margin), it was concluded that PR5I group response rate was non-inferior to INFANRIX hexa group response rate.
[30] - 1-sided

Secondary: Percentage of participants with injection-site and systemic adverse events (AEs) from Day 1 to Day 15 after any vaccination

Top of page

End point title

Percentage of participants with injection-site and systemic adverse events (AEs) from Day 1 to Day 15 after any vaccination

End point description

Global safety was assessed by measuring injection-site and systemic AEs reported daily on the Vaccination Report Card (VRC) by the parent(s) or legal representative from Day 1 to Day 15 (D1-D15) after each hexavalent vaccination. Solicited injection-site and systemic AEs were reported daily from Day 1 to Day 5 (D1-D5) after each hexavalent vaccination. AEs at injection sites were always considered as vaccine-related (Injection-Site Reactions (ISRs)). The investigator assessed whether systemic AEs were related (V-related) or not to the vaccine. All AEs (related and unrelated) are reported. The population analyzed was all randomised participants who received at least 1 vaccination and who had safety follow-up. Participants from site 0048 were excluded.

End point type

Secondary

End point timeframe

Day 1 to Day 15 after any vaccination

End point values	PR5I	INFANRIX™ hexa
Number of subjects analysed	610	603
Units: Percentage of participants
number (not applicable)
At least 1 ISR or systemic AE (D1-D15)	98.9	99.5
At least 1 ISR or V-related systemic AE (D1-D15)	98.5	98.8
At least 1 ISR (D1-D15)	92.1	91.0
At least 1 solicited ISR (D1-D5)	90.8	89.9
At least 1 systemic AE (D1-D15)	98.4	99.3
At least 1 V-related systemic AE (D1-D15)	95.6	96.5
At least 1 solicited systemic AE (D1-D5)	97.0	98.5
At least 1 V-related solicited systemic AE (D1-D5)	94.9	96.2

Risk difference: ISRs or systemic AEs

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[31]

Method

Parameter type

Risk difference (RD)

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-1.9

upper limit

0.4

Notes
[31] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Risk difference: ISRs or V-related sys. AEs

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[32]

Method

Parameter type

Risk difference (RD)

Point estimate

-0.3

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

1.1

Notes
[32] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Risk difference: At least 1 ISR

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[33]

Method

Parameter type

Risk difference (RD)

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.1

upper limit

4.3

Notes
[33] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Risk difference: At least 1 solicited ISR

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[34]

Method

Parameter type

Risk difference (RD)

Point estimate

0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

4.3

Notes
[34] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Risk difference: At least 1 systemic AE

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[35]

Method

Parameter type

Risk difference (RD)

Point estimate

-1

Confidence interval

level

95%

sides

2-sided

lower limit

-2.4

upper limit

0.3

Notes
[35] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Risk difference: At least 1 V-related sys. AE

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[36]

Method

Parameter type

Risk difference (RD)

Point estimate

-0.9

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

1.3

Notes
[36] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Risk difference: At least 1 solicited systemic AE

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[37]

Method

Parameter type

Risk difference (RD)

Point estimate

-1.5

Confidence interval

level

95%

sides

2-sided

lower limit

-3.3

upper limit

0.2

Notes
[37] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Risk difference: At least 1 V-related sol. sys. AE

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[38]

Method

Parameter type

Risk difference (RD)

Point estimate

-1.3

Confidence interval

level

95%

sides

2-sided

lower limit

-3.7

upper limit

1.1

Notes
[38] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Secondary: Percentage of participants reporting solicited ISRs from Day 1 to Day 5 after any vaccination

Top of page

End point title

Percentage of participants reporting solicited ISRs from Day 1 to Day 5 after any vaccination

End point description

Solicited ISRs were defined as injection-site erythema, injection-site pain, and injection-site swelling occurring from Day 1 (D1) to Day 5 (D5) after vaccination. AEs at injection sites were always considered as vaccine-related (Injection-Site Reactions (ISRs)). The population analyzed was all randomised participants who received at least 1 vaccination and who had safety follow-up. Participants from site 0048 were excluded.

End point type

Secondary

End point timeframe

Day 1 to Day 5 after any vaccination

End point values	PR5I	INFANRIX™ hexa
Number of subjects analysed	610	603
Units: Percentage of participants
number (not applicable)
Injection-site erythema	69.0	64.2
Injection-site pain	73.6	71.8
Injection-site swelling	56.9	52.9

Risk difference: Injection-site erythema

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[39]

Method

Parameter type

Risk difference (RD)

Point estimate

4.8

Confidence interval

level

95%

sides

2-sided

lower limit

-0.5

upper limit

10.1

Notes
[39] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Risk difference: Injection-site pain

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[40]

Method

Parameter type

Risk difference (RD)

Point estimate

1.8

Confidence interval

level

95%

sides

2-sided

lower limit

-3.2

upper limit

6.8

Notes
[40] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Risk difference: Injection-site swelling

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[41]

Method

Parameter type

Risk difference (RD)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-1.6

upper limit

9.6

Notes
[41] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Secondary: Percentage of participants reporting unsolicited ISRs from Day 1 to Day 15 after any vaccination

Top of page

End point title

Percentage of participants reporting unsolicited ISRs from Day 1 to Day 15 after any vaccination

End point description

Unsolicited ISRs with incidence ≥1% after any vaccination were reported daily on the VRC by the parent(s) or legal representative from (D1-D15). AEs at injection sites were always considered as vaccine-related ISRs. The population analyzed was all randomised participants who received at least 1 vaccination and who had safety follow-up. Participants from site 0048 were excluded.

End point type

Secondary

End point timeframe

Day 1 to Day 15 after any vaccination

End point values	PR5I	INFANRIX™ hexa
Number of subjects analysed	610	603
Units: Percentage of participants
number (not applicable)
Injection-site bruising	2.8	2.7
Injection-site haematoma	1.5	0.8
Injection-site haemorrhage	1.3	2.0
Injection-site induration	14.6	18.2
Injection-site nodule	1.3	1.5
Injection-site warmth	3.0	1.8

Risk difference: Injection-site bruising

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[42]

Method

Parameter type

Risk difference (RD)

Point estimate

0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.8

upper limit

2.1

Notes
[42] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Risk difference: Injection-site haematoma

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[43]

Method

Parameter type

Risk difference (RD)

Point estimate

0.6

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

2.1

Notes
[43] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Risk difference: Injection-site haemorrhage

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[44]

Method

Parameter type

Risk difference (RD)

Point estimate

-0.7

Confidence interval

level

95%

sides

2-sided

lower limit

-2.3

upper limit

0.8

Notes
[44] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Risk difference: Injection-site induration

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[45]

Method

Parameter type

Risk difference (RD)

Point estimate

-3.7

Confidence interval

level

95%

sides

2-sided

lower limit

-7.8

upper limit

0.5

Notes
[45] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Risk difference: Injection-site nodule

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[46]

Method

Parameter type

Risk difference (RD)

Point estimate

-0.2

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

1.3

Notes
[46] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Risk difference: Injection-site warmth

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[47]

Method

Parameter type

Risk difference (RD)

Point estimate

1.1

Confidence interval

level

95%

sides

2-sided

lower limit

-0.6

upper limit

Notes
[47] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Secondary: Percentage of participants reporting solicited systemic AE from Day 1 to Day 5 after any vaccination

Top of page

End point title

Percentage of participants reporting solicited systemic AE from Day 1 to Day 5 after any vaccination

End point description

Solicited systemic AEs were defined as crying, decreased appetite, irritability, pyrexia (rectal temperature ≥38.0°C), somnolence, and vomiting occurring from D1 to D5 after vaccination. The investigator assessed whether these systemic AEs were related or not to the vaccines. All (related and unrelated) AEs are reported. The population analyzed was all randomised participants who received at least 1 vaccination and who had safety follow-up. Participants from site 0048 were excluded.

End point type

Secondary

End point timeframe

Day 1 to Day 5 after any vaccination

End point values	PR5I	INFANRIX™ hexa
Number of subjects analysed	610	603
Units: Percentage of participants
number (not applicable)
Crying	85.4	87.9
Decreased appetite	63.9	67.0
Irritability	87.9	85.7
Pyrexia	71.5	73.1
Somnolence	76.9	80.1
Vomiting	31.8	31.0

Risk difference: Crying

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[48]

Method

Parameter type

Risk difference (RD)

Point estimate

-2.5

Confidence interval

level

95%

sides

2-sided

lower limit

-6.3

upper limit

1.4

Notes
[48] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Risk difference: Decreased appetite

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[49]

Method

Parameter type

Risk difference (RD)

Point estimate

-3.1

Confidence interval

level

95%

sides

2-sided

lower limit

-8.4

upper limit

2.3

Notes
[49] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Risk difference: Irritability

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[50]

Method

Parameter type

Risk difference (RD)

Point estimate

2.1

Confidence interval

level

95%

sides

2-sided

lower limit

-1.7

upper limit

Notes
[50] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Risk difference: Pyrexia

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[51]

Method

Parameter type

Risk difference (RD)

Point estimate

-1.7

Confidence interval

level

95%

sides

2-sided

lower limit

-6.7

upper limit

3.4

Notes
[51] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Risk difference: Somnolence

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[52]

Method

Parameter type

Risk difference (RD)

Point estimate

-3.2

Confidence interval

level

95%

sides

2-sided

lower limit

-7.8

upper limit

1.4

Notes
[52] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Risk difference: Vomiting

Statistical analysis description

PR5I minus INFANRIX™ hexa: Miettinen & Nurminen method

Comparison groups

PR5I v INFANRIX™ hexa

Number of subjects included in analysis

1213

Analysis specification

Pre-specified

Analysis type

other ^[53]

Method

Parameter type

Risk difference (RD)

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

-4.4

upper limit

Notes
[53] - If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.

Adverse events

Top of page

Timeframe for reporting adverse events

2 months after toddler dose (up to approximately age 14 months)

Adverse event reporting additional description

All Treated Participants. Participants from site 0048 were excluded.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

15.1

Reporting group title

INFANRIX hexa

Reporting group description

Reporting group title

PR5I

Reporting group description

The P R5I group received V419, Prevenar 13™, and RotaTeq™ at 2, 3, and 4 months; followed by V419 and ProQuad™ at 12 months, and Prevenar 13™ and ProQuad™ at 13 months.

Serious adverse events	INFANRIX hexa	PR5I
Total subjects affected by serious adverse events
subjects affected / exposed	22 / 605 (3.64%)	23 / 610 (3.77%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prolymphocytic leukaemia
subjects affected / exposed	0 / 605 (0.00%)	1 / 610 (0.16%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Abdominal injury
subjects affected / exposed	1 / 605 (0.17%)	0 / 610 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Concussion
subjects affected / exposed	1 / 605 (0.17%)	3 / 610 (0.49%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Skull fracture
subjects affected / exposed	0 / 605 (0.00%)	1 / 610 (0.16%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Subdural haematoma
subjects affected / exposed	0 / 605 (0.00%)	1 / 610 (0.16%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital, familial and genetic disorders
Benign familial neonatal convulsions
subjects affected / exposed	1 / 605 (0.17%)	0 / 610 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Convulsion
subjects affected / exposed	0 / 605 (0.00%)	1 / 610 (0.16%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Febrile convulsion
subjects affected / exposed	0 / 605 (0.00%)	1 / 610 (0.16%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	2 / 605 (0.33%)	2 / 610 (0.33%)
occurrences causally related to treatment / all	1 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Inguinal hernia
subjects affected / exposed	0 / 605 (0.00%)	1 / 610 (0.16%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Oesophagitis
subjects affected / exposed	1 / 605 (0.17%)	0 / 610 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Swollen tongue
subjects affected / exposed	1 / 605 (0.17%)	0 / 610 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Neuroendocrine cell hyperplasia of infancy
subjects affected / exposed	1 / 605 (0.17%)	0 / 610 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Muscle spasms
subjects affected / exposed	1 / 605 (0.17%)	0 / 610 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Bronchiolitis
subjects affected / exposed	2 / 605 (0.33%)	3 / 610 (0.49%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 605 (0.17%)	2 / 610 (0.33%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchitis viral
subjects affected / exposed	1 / 605 (0.17%)	0 / 610 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Exanthema subitum
subjects affected / exposed	0 / 605 (0.00%)	1 / 610 (0.16%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 605 (0.00%)	1 / 610 (0.16%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumococcal sepsis
subjects affected / exposed	1 / 605 (0.17%)	0 / 610 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 605 (0.00%)	1 / 610 (0.16%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	2 / 605 (0.33%)	2 / 610 (0.33%)
occurrences causally related to treatment / all	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	0 / 605 (0.00%)	1 / 610 (0.16%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory syncytial virus bronchiolitis
subjects affected / exposed	7 / 605 (1.16%)	3 / 610 (0.49%)
occurrences causally related to treatment / all	0 / 7	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	0 / 605 (0.00%)	1 / 610 (0.16%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Skin infection
subjects affected / exposed	1 / 605 (0.17%)	0 / 610 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urosepsis
subjects affected / exposed	0 / 605 (0.00%)	1 / 610 (0.16%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	INFANRIX hexa	PR5I
Total subjects affected by non serious adverse events
subjects affected / exposed	599 / 605 (99.01%)	603 / 610 (98.85%)
Nervous system disorders
Somnolence
subjects affected / exposed	485 / 605 (80.17%)	470 / 610 (77.05%)
occurrences all number	1058	1082
General disorders and administration site conditions
Crying
subjects affected / exposed	531 / 605 (87.77%)	523 / 610 (85.74%)
occurrences all number	1482	1543
Injection site erythema
subjects affected / exposed	430 / 605 (71.07%)	459 / 610 (75.25%)
occurrences all number	1517	1745
Injection site induration
subjects affected / exposed	127 / 605 (20.99%)	106 / 610 (17.38%)
occurrences all number	296	245
Injection site pain
subjects affected / exposed	456 / 605 (75.37%)	469 / 610 (76.89%)
occurrences all number	1637	1710
Injection site swelling
subjects affected / exposed	347 / 605 (57.36%)	384 / 610 (62.95%)
occurrences all number	1101	1214
Irritability
subjects affected / exposed	518 / 605 (85.62%)	537 / 610 (88.03%)
occurrences all number	1570	1639
Pyrexia
subjects affected / exposed	472 / 605 (78.02%)	471 / 610 (77.21%)
occurrences all number	1065	1072
Eye disorders
Conjunctivitis
subjects affected / exposed	32 / 605 (5.29%)	20 / 610 (3.28%)
occurrences all number	36	23
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	84 / 605 (13.88%)	98 / 610 (16.07%)
occurrences all number	113	129
Flatulence
subjects affected / exposed	39 / 605 (6.45%)	45 / 610 (7.38%)
occurrences all number	50	55
Vomiting
subjects affected / exposed	194 / 605 (32.07%)	205 / 610 (33.61%)
occurrences all number	333	328
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	38 / 605 (6.28%)	35 / 610 (5.74%)
occurrences all number	44	39
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	27 / 605 (4.46%)	35 / 610 (5.74%)
occurrences all number	32	42
Infections and infestations
Nasopharyngitis
subjects affected / exposed	35 / 605 (5.79%)	24 / 610 (3.93%)
occurrences all number	41	29
Otitis media
subjects affected / exposed	26 / 605 (4.30%)	32 / 610 (5.25%)
occurrences all number	30	33
Rhinitis
subjects affected / exposed	86 / 605 (14.21%)	82 / 610 (13.44%)
occurrences all number	101	102
Upper respiratory tract infection
subjects affected / exposed	76 / 605 (12.56%)	69 / 610 (11.31%)
occurrences all number	83	82
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	408 / 605 (67.44%)	401 / 610 (65.74%)
occurrences all number	718	752

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

10 Nov 2010

Amendment 1: The protocol template contained an error with respect to AE causality definitions in Table 3-3 of Section 3.4.5 Evaluating Adverse Events. Previously the protocol incorrectly grouped the "Possibly related" definition under the category of "No, there is not a reasonable possibility of vaccine relationship." The protocol was amended to correctly state the "Possibly related" definition under the category of "Yes, there is a reasonable possibility of vaccine relationship."

22 Dec 2010

Amendment 2: The primary reasons for this amendment were: 1) To revise the timing of when non-study vaccines could be received during the study; 2) the scale for grading injection-site pain and tenderness was revised to more directly reflect pain at the injection site; 3) the definition for a sub-responder to tetanus was redefined from a titer of < 0.01 IU/mL to < 0.1 IU/mL and 4) text regarding the analyses of serious adverse events within 7 and 14 days following any of doses 1 to 3 of PR5I or Control vaccines were added.

08 Jul 2011

Amendment 3: The primary reason for this amendment was to include administration of a second dose of ProQuad™ at the 13-month visit (Visit 6) in order to complete the series for ProQuad™, in alignment with the EU SmPC. In addition, the telephone contact at the end of the study (Visit 7) was extended to 28 days postvaccination to align with the recommended safety follow-up period for live virus vaccines.

08 Feb 2012

Amendment 4: The criterion for exclusion from the per-protocol immunogenicity analysis related to vaccine dosing was revised for clarity.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results:
A Phase III Randomized, Double-Blind, Active-Comparator Controlled Clinical Trial to Study the Safety, Tolerability, and Immunogenicity of V419 in Healthy Infants When Given at 2, 3, 4, and 12 Months (V419-007-03)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants vaccinated with PR5I with acceptable antibody (Ab) response to Haemophilus influenzae type b, diphtheria, tetanus, and poliovirus types 1, 2 & 3, at 5 months

Primary: Percentage of participants vaccinated with PR5I with acceptable antibody (Ab) response to Haemophilus influenzae type b, diphtheria, tetanus, and poliovirus types 1, 2 & 3, at 5 months

Primary: Percentage of participants vaccinated with PR5I with acceptable Ab response or seroresponse rates to all antigens contained in the PR5I vaccine one month after the toddler dose at 13 months

Primary: Percentage of participants vaccinated with PR5I with acceptable Ab response or seroresponse rates to all antigens contained in the PR5I vaccine one month after the toddler dose at 13 months

Primary: Percentage of participants vaccinated with PR5I compared with INFANRIX™ hexa with acceptable Ab response to Haemophilus influenzae type b, diphtheria, tetanus, and poliovirus types 1, 2 & 3, at 5 months

Primary: Percentage of participants vaccinated with PR5I compared with INFANRIX™ hexa with acceptable Ab response to Haemophilus influenzae type b, diphtheria, tetanus, and poliovirus types 1, 2 & 3, at 5 months

Primary: Percentage of participants vaccinated with PR5I compared with INFANRIX™ hexa with acceptable Ab response rates to Hepatitis B and seroresponse to Pertussis antigens Pt, FHA and PRN one month after the toddler dose at 13 months old

Primary: Percentage of participants vaccinated with PR5I compared with INFANRIX™ hexa with acceptable Ab response rates to Hepatitis B and seroresponse to Pertussis antigens Pt, FHA and PRN one month after the toddler dose at 13 months old

Secondary: Percentage of participants vaccinated with PR5I with acceptable Ab response to measles, mumps, rubella and varicella one month after the toddler dose of ProQuad at 13 months old

Secondary: Percentage of participants vaccinated with PR5I with acceptable Ab response to measles, mumps, rubella and varicella one month after the toddler dose of ProQuad at 13 months old

Secondary: Percentage of participants vaccinated with PR5I compared with INFANRIX™ hexa with acceptable Ab response to measles, mumps, rubella and varicella one month after the toddler dose of ProQuad at 13 months old

Secondary: Percentage of participants vaccinated with PR5I compared with INFANRIX™ hexa with acceptable Ab response to measles, mumps, rubella and varicella one month after the toddler dose of ProQuad at 13 months old

Secondary: Percentage of participants with injection-site and systemic adverse events (AEs) from Day 1 to Day 15 after any vaccination

Secondary: Percentage of participants with injection-site and systemic adverse events (AEs) from Day 1 to Day 15 after any vaccination

Secondary: Percentage of participants reporting solicited ISRs from Day 1 to Day 5 after any vaccination

Secondary: Percentage of participants reporting solicited ISRs from Day 1 to Day 5 after any vaccination

Secondary: Percentage of participants reporting unsolicited ISRs from Day 1 to Day 15 after any vaccination

Secondary: Percentage of participants reporting unsolicited ISRs from Day 1 to Day 15 after any vaccination

Secondary: Percentage of participants reporting solicited systemic AE from Day 1 to Day 5 after any vaccination

Secondary: Percentage of participants reporting solicited systemic AE from Day 1 to Day 5 after any vaccination

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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Clinical trials

Clinical Trial Results: A Phase III Randomized, Double-Blind, Active-Comparator Controlled Clinical Trial to Study the Safety, Tolerability, and Immunogenicity of V419 in Healthy Infants When Given at 2, 3, 4, and 12 Months (V419-007-03)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of participants vaccinated with PR5I with acceptable antibody (Ab) response to Haemophilus influenzae type b, diphtheria, tetanus, and poliovirus types 1, 2 & 3, at 5 months

Primary: Percentage of participants vaccinated with PR5I with acceptable antibody (Ab) response to Haemophilus influenzae type b, diphtheria, tetanus, and poliovirus types 1, 2 & 3, at 5 months

Primary: Percentage of participants vaccinated with PR5I with acceptable Ab response or seroresponse rates to all antigens contained in the PR5I vaccine one month after the toddler dose at 13 months

Primary: Percentage of participants vaccinated with PR5I with acceptable Ab response or seroresponse rates to all antigens contained in the PR5I vaccine one month after the toddler dose at 13 months

Primary: Percentage of participants vaccinated with PR5I compared with INFANRIX™ hexa with acceptable Ab response to Haemophilus influenzae type b, diphtheria, tetanus, and poliovirus types 1, 2 & 3, at 5 months

Primary: Percentage of participants vaccinated with PR5I compared with INFANRIX™ hexa with acceptable Ab response to Haemophilus influenzae type b, diphtheria, tetanus, and poliovirus types 1, 2 & 3, at 5 months

Primary: Percentage of participants vaccinated with PR5I compared with INFANRIX™ hexa with acceptable Ab response rates to Hepatitis B and seroresponse to Pertussis antigens Pt, FHA and PRN one month after the toddler dose at 13 months old

Primary: Percentage of participants vaccinated with PR5I compared with INFANRIX™ hexa with acceptable Ab response rates to Hepatitis B and seroresponse to Pertussis antigens Pt, FHA and PRN one month after the toddler dose at 13 months old

Secondary: Percentage of participants vaccinated with PR5I with acceptable Ab response to measles, mumps, rubella and varicella one month after the toddler dose of ProQuad at 13 months old

Secondary: Percentage of participants vaccinated with PR5I with acceptable Ab response to measles, mumps, rubella and varicella one month after the toddler dose of ProQuad at 13 months old

Secondary: Percentage of participants vaccinated with PR5I compared with INFANRIX™ hexa with acceptable Ab response to measles, mumps, rubella and varicella one month after the toddler dose of ProQuad at 13 months old

Secondary: Percentage of participants vaccinated with PR5I compared with INFANRIX™ hexa with acceptable Ab response to measles, mumps, rubella and varicella one month after the toddler dose of ProQuad at 13 months old

Secondary: Percentage of participants with injection-site and systemic adverse events (AEs) from Day 1 to Day 15 after any vaccination

Secondary: Percentage of participants with injection-site and systemic adverse events (AEs) from Day 1 to Day 15 after any vaccination

Secondary: Percentage of participants reporting solicited ISRs from Day 1 to Day 5 after any vaccination

Secondary: Percentage of participants reporting solicited ISRs from Day 1 to Day 5 after any vaccination

Secondary: Percentage of participants reporting unsolicited ISRs from Day 1 to Day 15 after any vaccination

Secondary: Percentage of participants reporting unsolicited ISRs from Day 1 to Day 15 after any vaccination

Secondary: Percentage of participants reporting solicited systemic AE from Day 1 to Day 5 after any vaccination

Secondary: Percentage of participants reporting solicited systemic AE from Day 1 to Day 5 after any vaccination

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase III Randomized, Double-Blind, Active-Comparator Controlled Clinical Trial to Study the Safety, Tolerability, and Immunogenicity of V419 in Healthy Infants When Given at 2, 3, 4, and 12 Months (V419-007-03)