Safety, Tolerability, and Immunogenicity of V419 in Healt... | NCT01480258

ID	Type	Description	Link
2010-021491-28	EudraCT Number
V419-008	Other Identifier	Merck

Name	Class
Merck Sharp & Dohme LLC	INDUSTRY

Safety, Tolerability, and Immunogenicity of V419 in Healt... | NCT01480258 | Trialant

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
PR5I	Experimental	Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.	Biological: PR5I Biological: Rotavirus vaccine Biological: Prevenar 13™
INFANRIX™ hexa	Active Comparator	Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.	Biological: Rotavirus vaccine Biological: Prevenar 13™ Biological: INFANRIX™ hexa

Interventions

Name	Type	Description	Arm Group Labels	Other Names
PR5I	Biological	DTaP-HB-IPV-Hib (Diphtheria, tetanus, pertussis [acellular, component], hepatitis B [recombinant DNA], polio virus [inactivated], and Haemophilus influenza type b conjugate vaccine [adsorbed]) Vaccine 0.5 mL intramuscular injection at 2, 4, and 11 to 12 months of age. Injection is to be administered in the upper anterolateral thigh, separate limb from the concomitant vaccine. PR5I is a liquid suspension hexavalent vaccine.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Acceptability of Antibody (Ab) Response or Seroresponse Rates to All Antigens Contained in PR5I Vaccine One Month After the Toddler Dose of PR5I (11 to 12 Months of Age)	Acceptability response rates were defined as Ab titre ≥1.0 μg/mL for Haemophilus influenzae type b (Hib) (polyribosylribitol phosphate, PRP); ≥10 mIU/mL for Hepatitis (HBsAg); ≥0.1 IU/mL for diphtheria and tetanus; ≥8 (1/dil) for inactive poliovirus type (IPV) 1, 2 & 3, and percentage of pertussis seroresponder participants (Pertussis toxoid [PT], Filamentous haemagglutinin [FHA], Fimbriae types 2 & 3 [FIM] and Pertactin [PRN]) 1 month Post-Toddler dose of PR5I. Seroresponse was defined: (1) If pre-Dose 1 Ab concentration (cc) was \	1 month after Toddler dose of PR51 (post-toddler dose)

Secondary Outcomes

Measure	Description	Time Frame
Non-inferiority of Antibody (Ab) Response Rate to Haemophilus Influenzae Type b (PRP) One Month After the 2nd Dose of PR5I (4 Months of Age) as Compared With INFANRIX Hexa	Percentage of participants with an Ab titre ≥1.0 μg/mL for Hib (polyribosylribitol phosphate, PRP) measured by radioimmunoassay (RIA) 1 month post-infant dose 2 of PR5I or INFANRIX hexa.	1 month after the 2nd dose (post-infant dose 2)

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
27288217	Derived	Silfverdal SA, Icardi G, Vesikari T, Flores SA, Pagnoni MF, Xu J, Liu GF, Stek JE, Boisnard F, Thomas S, Ziani E, Lee AW. A Phase III randomized, double-blind, clinical trial of an investigational hexavalent vaccine given at 2, 4, and 11-12 months. Vaccine. 2016 Jul 19;34(33):3810-6. doi: 10.1016/j.vaccine.2016.05.054. Epub 2016 Jun 18.

Arm/Group Information

ID	Title	Description
FG000	PR5I	Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
FG001	INFANRIX™ Hexa	Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

Periods

Title

Milestones

Reasons Not Completed

Infant Series

Type	Comment	Milestone Data
STARTED		FG000656 subjects FG001659 subjects
Vaccinated		FG000653 subjects FG001659 subjects
COMPLETED		FG000649 subjects FG001651 subjects
NOT COMPLETED		FG0007 subjects FG0018 subjects

Type	Comment	Reasons
Protocol Violation		FG0002 subjects FG0010 subjects
Physician Decision		FG0000 subjects FG001

Interim Period

Type	Comment	Milestone Data
STARTED		FG000649 subjects FG001651 subjects
COMPLETED		FG000639 subjects FG001

Toddler Dose

Type	Comment	Milestone Data
STARTED		FG000639 subjects FG001642 subjects
COMPLETED		FG000639 subjects FG001

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	PR5I	Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	Acceptability of Antibody (Ab) Response or Seroresponse Rates to All Antigens Contained in PR5I Vaccine One Month After the Toddler Dose of PR5I (11 to 12 Months of Age)	Acceptability response rates were defined as Ab titre ≥1.0 μg/mL for Haemophilus influenzae type b (Hib) (polyribosylribitol phosphate, PRP); ≥10 mIU/mL for Hepatitis (HBsAg); ≥0.1 IU/mL for diphtheria and tetanus; ≥8 (1/dil) for inactive poliovirus type (IPV) 1, 2 & 3, and percentage of pertussis seroresponder participants (Pertussis toxoid [PT], Filamentous haemagglutinin [FHA], Fimbriae types 2 & 3 [FIM] and Pertactin [PRN]) 1 month Post-Toddler dose of PR5I. Seroresponse was defined: (1) If pre-Dose 1 Ab concentration (cc) was \	Participants who met the inclusion criteria, were not protocol violators, received PR51 vaccinations within acceptable day ranges, and had a blood draw sample window of Days 28 to 51 following the Toddler dose. Participants receiving INFANRIX™ hexa were excluded from the acceptability analyses.	Posted		Number	95% Confidence Interval	Percentage of participants		1 month after Toddler dose of PR51 (post-toddler dose)

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	PR5I	Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Idiopathic thrombocytopenic purpura	Blood and lymphatic system disorders	MedDRA 16.0	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Senior Vice President, Global Clinical Development	Merck, Sharp & Dohme Corp.	1-800-672-6372		ClinicalTrialsDisclosure@merck.com

Condition Browse Module

ID	Term
D001424	Bacterial Infections
D014777	Virus Diseases
D004165	Diphtheria
D014917	Whooping Cough
D013742	Tetanus
D006509	Hepatitis B
D006192	Haemophilus Infections
D011051	Poliomyelitis

ID	Term
D001423	Bacterial Infections and Mycoses
D007239	Infections
D003354	Corynebacterium Infections
D000193	Actinomycetales Infections

Intervention Browse Module

ID	Term
C000617220	Vaxelis
D022243	Rotavirus Vaccines
C538862	13-valent pneumococcal vaccine

ID	Term
D014765	Viral Vaccines
D014612	Vaccines
D001688	Biological Products
D045424	Complex Mixtures

Type	Comment	Reasons
Lost to Follow-up		FG0000 subjects FG0012 subjects
Physician Decision		FG0001 subjects FG0010 subjects
Protocol Violation		FG0000 subjects FG0011 subjects
Withdrawal by Subject		FG0009 subjects FG0016 subjects

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

Finland

Title	Measurements
	BG000459 BG001460 BG002919

Italy

Title	Measurements
	BG000132 BG001132 BG002264

Sweden

Title	Measurements
	BG00065 BG00167 BG002132

ID	Title	Description
OG000	PR5I	Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
OG001	INFANRIX™ Hexa	Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

Title

Denominators

Categories

Anti-PRP ≥1.0 μg/mL

- ParticipantsOG000454
- ParticipantsOG0010

Title	Measurements
	OG00089.87(86.72 to 92.49)

Anti-HBsAg ≥10 mIU/mL

- ParticipantsOG000377
- ParticipantsOG0010

Title	Measurements
	OG00098.14(96.21 to 99.25)

Anti-Diphtheria ≥0.1 IU/mL

- ParticipantsOG000590
- ParticipantsOG0010

Title	Measurements
	OG00098.64(97.35 to 99.41)

Anti-Tetanus ≥0.1 IU/mL

- ParticipantsOG000589
- ParticipantsOG0010

Title	Measurements
	OG00099.83(99.06 to 100.00)

Anti-PT seroresponse

- ParticipantsOG000566
- ParticipantsOG0010

Title	Measurements
	OG00099.12(97.95 to 99.71)

Anti-FHA seroresponse

- ParticipantsOG000582
- ParticipantsOG0010

Title	Measurements
	OG00097.42(95.78 to 98.55)

Anti-FIM seroresponse

- ParticipantsOG000581
- ParticipantsOG0010

Title	Measurements
	OG00098.28(96.86 to 99.17)

Anti-PRN seroresponse

- ParticipantsOG000582
- ParticipantsOG0010

Title	Measurements
	OG00096.91(95.16 to 98.16)

Anti-IPV1 ≥1:8 dilution

- ParticipantsOG000591
- ParticipantsOG0010

Title	Measurements
	OG00099.32(98.28 to 99.82)

Anti-IPV2 ≥1:8 dilution

- ParticipantsOG000591
- ParticipantsOG0010

Title	Measurements
	OG00099.83(99.06 to 100.00)

Anti-IPV3 ≥1:8 dilution

- ParticipantsOG000590
- ParticipantsOG0010

Title	Measurements
	OG00099.49(98.52 to 99.90)

Group IDs	Group Description	Statistical Method	P-Value	P-Value Comment	Non-Inferiority Type	Non-Inferiority Comment
OG000	Anti-PRP ≥ 1.0 μg/mL	Clopper and Pearson	<0.001	One-sided p-value	Other	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 75%.
OG000	Anti-HBsAg ≥10 mIU/mL	Clopper and Pearson	<0.001	One-sided p-value	Other	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 75%.
OG000	Anti-Diphtheria ≥0.1 IU/mL	Clopper and Pearson	<0.001	One-sided p-value	Other	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 75%.
OG000	Anti-Tetanus ≥0.1 IU/mL	Clopper and Pearson	<0.001	One-sided p-value	Other	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 75%.
OG000	Anti-PT seroresponse	Clopper and Pearson	<0.001	One-sided p-value	Other	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 75%.
OG000	Anti-FHA seroresponse	Clopper and Pearson	<0.001	One-sided p-value	Other	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 75%.
OG000	Anti-FIM seroresponse	Clopper and Pearson	<0.001	One-sided p-value	Other	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 75%.
OG000	Anti-PRN seroresponse	Clopper and Pearson	<0.001	One-sided p-value	Other	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 75%.
OG000	Anti-IPV1 ≥1:8 dilution	Clopper and Pearson	<0.001	One-sided p-value	Other	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 75%.
OG000	Anti-IPV2 ≥1:8 dilution	Clopper and Pearson	<0.001	One-sided p-value	Other	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 75%.
OG000	Anti-IPV3 ≥1:8 dilution	Clopper and Pearson	<0.001	One-sided p-value	Other	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 75%.

Secondary

Non-inferiority of Antibody (Ab) Response Rate to Haemophilus Influenzae Type b (PRP) One Month After the 2nd Dose of PR5I (4 Months of Age) as Compared With INFANRIX Hexa

Percentage of participants with an Ab titre ≥1.0 μg/mL for Hib (polyribosylribitol phosphate, PRP) measured by radioimmunoassay (RIA) 1 month post-infant dose 2 of PR5I or INFANRIX hexa.

Participants who received 2nd dose in the Infant series and had a blood draw sample window of Days 28 to 51 post-infant dose 2.

Posted

Number

Percentage of participants

1 month after the 2nd dose (post-infant dose 2)

ID	Title	Description
OG000	PR5I	Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
OG001	INFANRIX™ Hexa	Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

Units	Counts
Participants	OG000609 OG001592

Title

Denominators

Categories

Title	Measurements
	OG00072.86 OG00126.66

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Miettinen & Nurminen		<0.001	Stratification by country.	Difference in percentages	46.20			2-Sided	95	41.05	51.06					Non-Inferiority	If the lower bound of the 95% confidence interval (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.

Secondary

Superiority of Antibody (Ab) Response Rates to Haemophilus Influenzae Type b (PRP) One Month After the 2nd Dose of PR5I (4 Months of Age) as Compared With INFANRIX Hexa

Percentage of participants with an Ab titre ≥1.0 μg/mL for Hib (polyribosylribitol phosphate, PRP) measured by RIA 1 month post-infant dose 2 of PR5I or INFANRIX hexa.

Participants who received 2nd dose in the Infant series and had a blood draw sample window of Days 28 to 51 post-infant dose 2.

Posted

Number

Percentage of participants

1 month after the 2nd dose (post-infant dose 2)

ID	Title	Description
OG000	PR5I	Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
OG001	INFANRIX™ Hexa	Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

Units	Counts
Participants	OG000609 OG001592

Title

Denominators

Categories

Title	Measurements
	OG00072.86 OG00126.66

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Miettinen & Nurminen	Stratification by country.	<0.001		Difference in percentages	46.20			2-Sided	95	41.05	51.06					Superiority	If the lower bound of the 95% CI was greater than 0, it was concluded that PR5I group response rate was superior to INFANRIX hexa group response rate.

Secondary

Non-inferiority Ab Response Rates to PR5I Antigens One Month After the Toddler Dose of PR5I (11 to 12 Months of Age) as Compared With INFANRIX Hexa

Percentage of participants with pre-specified Ab titre for PRP, HBsAg, diphtheria, tetanus, IPV1, 2 & 3, and percentage of pertussis seroresponder participants (PT, FHA, FIM and PRN) 1 month post-toddler dose were calculated based on the method by Miettinen and Nurminen stratified by country. Seroresponse was defined: (1) If pre-Dose 1 Ab cc was \

Participants who met the inclusion criteria, were not protocol violators, received vaccinations within acceptable day ranges, and had a blood draw sample window of Days 28 to 51 following the Toddler dose.

Posted

Number

Percentage of participants

1 month after Toddler dose (post-toddler dose)

ID	Title	Description
OG000	PR5I	Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
OG001	INFANRIX™ Hexa	Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

Units	Counts
Participants	OG000638 OG001642

Title

Denominators

Categories

Anti-PRP ≥1.0 μg/mL

- ParticipantsOG000454
- ParticipantsOG001478

Title	Measurements
	OG00089.80

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Non-inferiority for PRP	Miettinen & Nurminen with stratification	Statistical analysis was based on the Miettinen & Nurminen method stratified by country.	<0.001		Difference in percentages	-1.27			2-Sided	95	-5.13	2.52					Non-Inferiority	The estimate of the difference between PR5I & INFANRIX hexa groups in PRP response rate (based on Ab titre ≥1.0 μg/mL) was calculated with its 1-sided P-value & 2-sided 95% CI. 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.

Secondary

Non-inferiority of Rotavirus Response (Geometric Mean Titer, GMT) One Month After the 2nd Dose of Rotarix (4 Months of Age) Administered Concomitantly With PR5I Versus INFANRIX Hexa

Antibody titres expressed in units/mL were measured for Rotavirus IgA by Enzyme Immunoassay (EIA), 1 month after the 2nd dose of Rotarix, administered concomitantly with PR5I or INFANRIX hexa (Post-Dose 2). The 95% CI for GMT was based on the t-distribution of the natural log-transformed antibody titer.

Participants who received dose 2 of Rotarix.

Posted

Geometric Mean

95% Confidence Interval

Titre (units/mL)

1 month after the 2nd dose of Rotarix, administered concomitantly with PR5I or INFANRIX hexa (Post-Dose 2)

ID	Title	Description
OG000	PR5I	Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
OG001	INFANRIX™ Hexa	Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

Units	Counts
Participants	OG000160 OG001171

Title

Denominators

Categories

Title	Measurements
	OG00096.41(71.69 to 129.65) OG001122.24(92.48 to 161.58)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		ANCOVA		0.011		Geometric Mean Titre (GMT) ratio	0.80			2-Sided	95	0.54	1.20					Non-Inferiority	The estimate for anti-rotavirus IgA GMT ratio (PR5I group/INFANRIX hexa group) was calculated with its 1-sided P-value and 2-sided 95% CI. If the lower bound of the 95% CI for GMT ratio was greater than 0.50 (non-inferiority margin), it was concluded that the Rotarix antigen response in the PR5I group was not inferior to the Rotarix antigen response in the INFANRIX hexa group.

Secondary

Number of Participants Who Experienced an Adverse Event (AE) From Day 1 to Day 15 After Any Vaccination

Injection-site and systemic AEs were reported daily on the Vaccination Report Card (VRC) by the parent(s) or legal representative from Day 1 (D1) to D15 after each vaccination. Solicited injection site and systemic AEs were reported daily from D1 to D5 after each vaccination. AEs at injection sites were always considered as vaccine-related (V-related) (Injection-Site Reactions [ISRs]). The investigator had to assess whether systemic AEs were related or not to the vaccine. All AEs (related and unrelated) are displayed here.

All randomized participants who received at least 1 vaccination and who had safety follow-up.

Posted

Number

Percentage of participants

Solicited AEs: up to 5 days (Days 1-5 after any vaccination); unsolicited AEs: up to 15 days (Day 1-15 after any vaccination)

ID	Title	Description
OG000	PR5I	Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
OG001	INFANRIX™ Hexa	Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

Units	Counts
Participants	OG000653 OG001659

Title

Denominators

Categories

At least 1 ISR or systemic AE (D1-D15)

Title	Measurements
	OG00099.5 OG00199.2

At least 1 ISR or V-related systemic AE (D1-D15)

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	ISR or systemic AE					Risk Difference (RD)	0.3			2-Sided	95	-0.7	1.4					Other	The risk differences between groups (PR5I group - INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. The aim of the 95% CI was to investigate an overall trend and not any specific difference. If 0.0 was excluded from the 95% CI, the trend could not be ruled out.

Secondary

Percentage of Participants Reporting Solicited ISRs From D1 to D5 After Any Vaccination

Adverse events at injection sites were always considered as related to vaccine (Injection-Site Reactions [ISRs]). Solicited ISRs were defined as injection-site erythema, injection-site pain, and injection-site swelling occurring from D1 to D5 after vaccination.

All randomised participants who received at least 1 vaccination and who had safety follow-up.

Posted

Number

Percentage of participants

Up to 5 days (Day 1 to Day 5 following vaccination)

ID	Title	Description
OG000	PR5I	Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
OG001	INFANRIX™ Hexa	Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

Units	Counts
Participants	OG000653 OG001659

Title

Denominators

Categories

Injection-site erythema

Title	Measurements
	OG00068.6 OG00160.4

Injection-site pain

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Injection-site erythema					Risk Difference (RD)	8.2			2-Sided	95	3.0	13.3					Other	The risk differences between groups (PR5I group - INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. The aim of the 95% CI was to investigate whether an overall trend of risk differences existed. 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 D1 to D15 After Any Vaccination

Adverse events at injection sites were always considered as related to vaccine (Injection-Site Reactions {ISRs]). Unsolicited ISRs occurring from Day 1 (D1) to D15 after any vaccination were reported daily on the VRC by the parent(s) or legal representative. Unsolicited ISRs with incidence ≥1% are reported below.

All randomised participants who received at least 1 vaccination and who had safety follow-up.

Posted

Number

Percentage of participants

From D1 to D15 after any vaccination

ID	Title	Description
OG000	PR5I	Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
OG001	INFANRIX™ Hexa	Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

Units	Counts
Participants	OG000653 OG001659

Title

Denominators

Categories

Injection-site bruising

Title	Measurements
	OG0000.9 OG0012.0

Injection-site haemorrhage

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Injection-site bruising					Risk Difference (RD)	-1.1			2-Sided	95	-2.5	0.3					Other	The risk differences between groups (PR5I group - INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. The aim of the 95% CI was to investigate an overall trend and not any specific difference. If 0.0 was excluded from the 95% CI, the trend could not be ruled out.

Secondary

Percentage of Participants Reporting Solicited Adverse Events (AEs) From D1 to D5 After Any Vaccination

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 had to assess whether these systemic AEs were related or not to the vaccines. All (related and unrelated) are displayed here.

All randomised participants who received at least 1 vaccination and who had safety follow-up.

Posted

Number

Percentage of participants

Up to 5 days (from D1 to D5 after any vaccination)

ID	Title	Description
OG000	PR5I	Infant series: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: PR5I 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.
OG001	INFANRIX™ Hexa	Infant series: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 2 and 4 months of age, and rotavirus vaccine (either Rotarix™ 1.5 mL oral dose at 2 and 4 months of age [subset 1] or RotaTeq™ 2 mL oral dose at 2, 4 and 5 months of age [subset 2]). Toddler dose: INFANRIX™ hexa 0.5 mL injection + Prevenar 13™ 0.5 mL injection administered at 11 to 12 months of age.

Units	Counts
Participants	OG000653 OG001659

Title

Denominators

Categories

Crying

Title	Measurements
	OG00089.3 OG00187.1

Decreased appetite

Title	Measurements
	OG000

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	Crying					Risk Difference (RD)	2.2			2-Sided	95	-1.3	5.7					Other	The risk differences between groups (PR5I group - INFANRIX hexa group) and their 2-sided 95% CI were calculated for the above criteria based on the unstratified Miettinen & Nurminen method. The aim of the 95% CI was to investigate whether an overall trend of risk differences existed. If the 95% CI for the risk differences included 0.0, the numerical differences were not considered significant.