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Clinical Trial Results:
A phase III open-label randomised study, to evaluate the immunogenicity and safety of the concomitant administration of V419 (PR5I) given at 2, 3 and 4 months of age with two types of meningococcal serogroup C conjugate (MCC) vaccines given at 3 and 4 months of age, and followed by the administration at 12 months of age of a combined Haemophilus influenzae type b-MCC vaccine.

Summary
EudraCT number	2011-002413-11
Trial protocol	GB
Global end of trial date	27 Sep 2013

Results information
Results version number	v1
This version publication date	27 Apr 2016
First version publication date	02 Aug 2015
Other versions	v2

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

PRI01C

ISRCTN number

US NCT number

NCT01553279

WHO universal trial number (UTN)

Sponsor organisation name

Sanofi Pasteur MSD S.N.C.

Sponsor organisation address

162 avenue Jean Jaurès - CS 50712, Lyon Cedex 07, France, 69367

Public contact

Clinical Trials Disclosure, Sanofi Pasteur MSD S.N.C., ClinicalTrialsDisclosure@spmsd.com

Scientific contact

Clinical Trials Disclosure, Sanofi Pasteur MSD S.N.C., ClinicalTrialsDisclosure@spmsd.com

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

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

27 Sep 2013

Is this the analysis of the primary completion data?

Yes

Primary completion date

27 Sep 2013

Global end of trial reached?

Yes

Global end of trial date

27 Sep 2013

Was the trial ended prematurely?

Main objective of the trial

To evaluate the concomitant administration of PR5I with 2 types of MCC vaccines (MCC-TT and MCC-CRM) to healthy infants at 3 and 4 months of age in terms of antibody seroprotection rate (SPR) to MCC.

Protection of trial subjects

Healthy subjects with known or suspected hypersensitivity to any of the study vaccines’ component or history of a life-threatening reaction to a vaccine containing the same substances as the study vaccines were excluded. Vaccines were administered by qualified study personnel. After each vaccination, subjects were kept under observation for at least 30 minutes to ensure their safety. Adequate treatment provisions, including epinephrine, were to be available for immediate use if an anaphylactic or anaphylactoid reaction occurred.

Background therapy

Evidence for comparator

Actual start date of recruitment

30 Mar 2012

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 284

Worldwide total number of subjects

284

EEA total number of subjects

284

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)

284

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

Study subjects were enrolled in 11 active centres in the United Kingdom (UK).

Screening details

292 subjects were screened. 284 subjects were randomised. 282 subjects received all 3 doses of PR5I vaccine and all 2 doses of MCC vaccines (period 1). 281 subjects completed period 1 of the study. 5 subjects discontinued between periods 1 & 2. 276 subjects entered period 2 and received Hib-MCC vaccine. 266 subjects completed the study.

Period 1 title

Infant doses

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Blinding implementation details

Not applicable as this study was open-label. Serology tests were performed by laboratory staffs that were blinded for the group to which each subject was randomised.

Are arms mutually exclusive

Yes

MCC-TT (period 1)

Arm description

Subjects received: # 3 doses of PR5I vaccine (DTaP-HB-IPV-Hib = Diphtheria, Tetanus, Pertussis (acellular, component), Hepatitis B (rDNA), Poliomyelitis (inactivated) & Haemophilus influenzae type b conjugate vaccine (adsorbed)) by intramuscular (IM) route: dose 1 at 2 months of age (Visit 1, V1), dose 2 at 3 months of age (V2) & dose 3 at 4 months of age (V3). # 2 doses of MCC-TT vaccine (NeisVac-C® = Meningococcal group C polysaccharide Conjugate vaccine to tetanus toxoid) by IM route: dose 1 at 3 months of age (V2) & dose 2 at 4 months of age (V3). # As routine vaccination, subjects also received PCV-13 vaccine (Prevenar 13® = Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)) by IM route: dose 1 at 2 months of age (V1) & dose 2 at 4 months of age (V3). Subjects were blood sampled (i) before vaccination (V1), (ii) 1 month (28-44 days) Post-Dose 1 of MCC-TT vaccine (V3) & (iii) 1 month Post-Dose 2 of MCC-TT vaccine = 1 month Post-Dose 3 of PR5I vaccine (V4).

Arm type

Experimental

Investigational medicinal product name

PR5I vaccine

Investigational medicinal product code

DTaP-HB-IPV-Hib

Other name

V419

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, IM route (left thigh), 3 doses: dose 1 at 2 months of age (V1), dose 2 at 3 months of age (V2), and dose 3 at 4 months of age (V3).

Investigational medicinal product name

NeisVac-C®

Investigational medicinal product code

MCC-TT vaccine

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, IM route (right thigh, separated by at least 5 centimetres from PCV-13 vaccine injection-site), 2 doses: dose 1 at 3 months of age (V2), and dose 2 at 4 months of age (V3).

Investigational medicinal product name

Prevenar 13®

Investigational medicinal product code

PCV-13 vaccine

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, IM route (right thigh, separated by at least 5 centimetres from MCC-TT vaccine injection-site), 2 doses: dose 1 at 2 months of age (V1), and dose 2 at 4 months of age (V3).

MCC-CRM (period 1)

Arm description

Subjects received: # 3 doses of PR5I vaccine (DTaP-HB-IPV-Hib = Diphtheria, Tetanus, Pertussis (acellular, component), Hepatitis B (rDNA), Poliomyelitis (inactivated) & Haemophilus influenzae type b conjugate vaccine (adsorbed)) by IM route: dose 1 at 2 months of age (V1), dose 2 at 3 months of age (V2) & dose 3 at 4 months of age (V3). # 2 doses of MCC-CRM vaccine (Menjugate® = Meningococcal group C Conjugate vaccine to CRM-197) by IM route: dose 1 at 3 months of age (V2) & dose 2 at 4 months of age (V3). # As routine vaccination, subjects also received PCV-13 vaccine (Prevenar 13® = Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)) by IM route: dose 1 at 2 months of age (V1) & dose 2 at 4 months of age (V3). Subjects were blood sampled (i) before vaccination (V1), (ii) 1 month (28-44 days) Post-Dose 1 of MCC-CRM vaccine (V3) & (iii) 1 month Post-Dose 2 of MCC-CRM vaccine = 1 month Post-Dose 3 of PR5I vaccine (V4).

Arm type

Experimental

Investigational medicinal product name

PR5I vaccine

Investigational medicinal product code

DTaP-HB-IPV-Hib

Other name

V419

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, IM route (left thigh), 3 doses: dose 1 at 2 months of age (V1), dose 2 at 3 months of age (V2), and dose 3 at 4 months of age (V3).

Investigational medicinal product name

Menjugate®

Investigational medicinal product code

MCC-CRM vaccine

Other name

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, IM route (right thigh, separated by at least 5 centimetres from PCV-13 vaccine injection-site), 2 doses: dose 1 at 3 months of age (V2), and dose 2 at 4 months of age (V3).

Investigational medicinal product name

Prevenar 13®

Investigational medicinal product code

PCV-13 vaccine

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, IM route (right thigh, separated by at least 5 centimetres from MCC-CRM vaccine injection-site), 2 doses: dose 1 at 2 months of age (V1), and dose 2 at 4 months of age (V3).

Number of subjects in period 1	MCC-TT (period 1)	MCC-CRM (period 1)
Started	142	142
Completed	140	141
Not completed	2	1
Consent withdrawn by subject	1	1
Lost to follow-up	1	-

Period 2 title

Toddler dose

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Not blinded

Blinding implementation details

Not applicable as this study was open-label. Serology tests were performed by laboratory staffs that were blinded for the group to which each subject was randomised.

Are arms mutually exclusive

Yes

MCC-TT (period 2)

Arm description

# Subjects of the "MCC-TT (period 1)" group received 1 toddler dose of Hib-MCC vaccine (Menitorix® = Haemophilus influenzae type b and Meningococcal group C conjugate vaccine) by IM route at 12 months of age (V5). # As routine vaccination, subjects also received 1 dose of PCV-13 vaccine (Prevenar 13® = Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)) + 1 dose of MMR vaccine (M-M-RvaxPRO® = Measles, Mumps, and Rubella vaccine) by IM route at 12 months of age (V5). Subjects were blood sampled (i) before toddler dose of Hib-MCC vaccine = Pre Hib-MCC dose (V5), and (ii) 1 month (28-44 days) after toddler dose of Hib-MCC vaccine = Post Hib-MCC dose (V6).

Arm type

Experimental

Investigational medicinal product name

Menitorix®

Investigational medicinal product code

Hib-MCC vaccine

Other name

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, IM route (left thigh), 1 dose at 12 months of age (V5).

Investigational medicinal product name

Prevenar 13®

Investigational medicinal product code

PCV-13 vaccine

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, IM route (right thigh, separated by at least 5 centimetres from MMR vaccine injection-site), 1 dose at 12 months of age (V5).

Investigational medicinal product name

M-M-RvaxPRO®

Investigational medicinal product code

MMR vaccine

Other name

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, IM route (right thigh, separated by at least 5 centimetres from PCV-13 vaccine injection-site), 1 dose at 12 months of age (V5).

MCC-CRM (period 2)

Arm description

# Subjects of the "MCC-CRM (period 1)" group received 1 toddler dose of Hib-MCC vaccine (Menitorix® = Haemophilus influenzae type b and Meningococcal group C conjugate vaccine) by IM route at 12 months of age (V5). # As routine vaccination, subjects also received 1 dose of PCV-13 vaccine (Prevenar 13® = Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)) + 1 dose of MMR vaccine (M-M-RvaxPRO® = Measles, Mumps, and Rubella vaccine) by IM route at 12 months of age (V5). Subjects were blood sampled (i) before toddler dose of Hib-MCC vaccine = Pre Hib-MCC dose (V5), and (ii) 1 month (28-44 days) after toddler dose of Hib-MCC vaccine = Post Hib-MCC dose (V6).

Arm type

Experimental

Investigational medicinal product name

Menitorix®

Investigational medicinal product code

Hib-MCC vaccine

Other name

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, IM route (left thigh), 1 dose at 12 months of age (V5).

Investigational medicinal product name

Prevenar 13®

Investigational medicinal product code

PCV-13 vaccine

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, IM route (right thigh, separated by at least 5 centimetres from MMR vaccine injection-site), 1 dose at 12 months of age (V5).

Investigational medicinal product name

M-M-RvaxPRO®

Investigational medicinal product code

MMR vaccine

Other name

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, IM route (right thigh, separated by at least 5 centimetres from PCV-13 vaccine injection-site), 1 dose at 12 months of age (V5).

Number of subjects in period 2 ^[1]	MCC-TT (period 2)	MCC-CRM (period 2)
Started	137	139
Completed	134	132
Not completed	3	7
Consent withdrawn by subject	-	5
Lost to follow-up	3	2

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: # In the MCC-TT arm, 3 subjects discontinued the study between the Infant doses and the Toddler dose: 1 "lost of follow-up" and 2 "consent withdrawn by subject". # In the MCC-CRM arm, 2 subjects discontinued the study between the Infant doses and the Toddler dose: 2 "consent withdrawn by subject".

Baseline characteristics

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Reporting group title

MCC-TT (period 1)

Reporting group description

Reporting group title

MCC-CRM (period 1)

Reporting group description

Subjects received: # 3 doses of PR5I vaccine (DTaP-HB-IPV-Hib = Diphtheria, Tetanus, Pertussis (acellular, component), Hepatitis B (rDNA), Poliomyelitis (inactivated) & Haemophilus influenzae type b conjugate vaccine (adsorbed)) by IM route: dose 1 at 2 months of age (V1), dose 2 at 3 months of age (V2) & dose 3 at 4 months of age (V3). # 2 doses of MCC-CRM vaccine (Menjugate® = Meningococcal group C Conjugate vaccine to CRM-197) by IM route: dose 1 at 3 months of age (V2) & dose 2 at 4 months of age (V3). # As routine vaccination, subjects also received PCV-13 vaccine (Prevenar 13® = Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)) by IM route: dose 1 at 2 months of age (V1) & dose 2 at 4 months of age (V3). Subjects were blood sampled (i) before vaccination (V1), (ii) 1 month (28-44 days) Post-Dose 1 of MCC-CRM vaccine (V3) & (iii) 1 month Post-Dose 2 of MCC-CRM vaccine = 1 month Post-Dose 3 of PR5I vaccine (V4).

Reporting group values	MCC-TT (period 1)	MCC-CRM (period 1)	Total
Number of subjects	142	142	284
Age categorical
Age at Visit 1.
Units: Subjects
Infants and toddlers (mini: 47 days-maxi: 76 days)	142	142	284
Age continuous
Age in days calculated as (date of vaccination dose 1-date of birth)+1.
Units: days
arithmetic mean (standard deviation)	62.6 ( 6.7 )	61.6 ( 7.2 )	-
Gender categorical
Units: Subjects
Female	62	67	129
Male	80	75	155

End points

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Reporting group title

MCC-TT (period 1)

Reporting group description

Reporting group title

MCC-CRM (period 1)

Reporting group description

Subjects received: # 3 doses of PR5I vaccine (DTaP-HB-IPV-Hib = Diphtheria, Tetanus, Pertussis (acellular, component), Hepatitis B (rDNA), Poliomyelitis (inactivated) & Haemophilus influenzae type b conjugate vaccine (adsorbed)) by IM route: dose 1 at 2 months of age (V1), dose 2 at 3 months of age (V2) & dose 3 at 4 months of age (V3). # 2 doses of MCC-CRM vaccine (Menjugate® = Meningococcal group C Conjugate vaccine to CRM-197) by IM route: dose 1 at 3 months of age (V2) & dose 2 at 4 months of age (V3). # As routine vaccination, subjects also received PCV-13 vaccine (Prevenar 13® = Pneumococcal polysaccharide conjugate vaccine (13-valent, adsorbed)) by IM route: dose 1 at 2 months of age (V1) & dose 2 at 4 months of age (V3). Subjects were blood sampled (i) before vaccination (V1), (ii) 1 month (28-44 days) Post-Dose 1 of MCC-CRM vaccine (V3) & (iii) 1 month Post-Dose 2 of MCC-CRM vaccine = 1 month Post-Dose 3 of PR5I vaccine (V4).

Reporting group title

MCC-TT (period 2)

Reporting group description

Reporting group title

MCC-CRM (period 2)

Reporting group description

Subject analysis set title

Combined vaccine groups

Subject analysis set type

Sub-group analysis

Subject analysis set description

Combined vaccine groups = MCC-TT period 1 and MCC-CRM period 1 combined groups, i.e., all randomised subjects excluding those with protocol deviation which could interfere with the immunogenicity evaluation.

Primary: Acceptability of the seroprotection rate (SPR) to MCC 1 month Post-Dose 2 of MCC-TT or MCC-CRM vaccine administered concomitantly with PR5I vaccine (V4)

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End point title

Acceptability of the seroprotection rate (SPR) to MCC 1 month Post-Dose 2 of MCC-TT or MCC-CRM vaccine administered concomitantly with PR5I vaccine (V4) ^[1]

End point description

The SPR to MCC (proportion of subjects with anti-MCC antibody (Ab) titre ≥8 (1/dil)) was determined 1 month Post-Dose 2 of MCC-TT or MCC-CRM vaccine administered concomitantly with PR5I vaccine (V4). Anti-MCC Ab titres were measured by serum bactericidal antibody with rabbit complement (rSBA). Analysis was done on the Period 1 Per Protocol Set (PPS), i.e., all randomised subjects excluding those with protocol deviation which could interfere with the immunogenicity evaluation. Note: (N=***, ***) represents the number of assessed subjects in the "MCC-TT" and "MCC-CRM" groups, respectively.

End point type

Primary

End point timeframe

1 month Post-Dose 2 of MCC-TT or MCC-CRM vaccine administered concomitantly with PR5I vaccine (V4).

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: There was no comparison between groups in this end point. The SPR to MCC was considered as acceptable if the lower bounds of the 2-sided 95% CI for the response rates were greater than 90% (i.e., the prespecified acceptability threshold). Analysis was based on the 2-sided 95% CI with adjustment for multiplicity for single group proportion, calculated using the exact binomial method for binary variables as defined by D. Collet. Acceptability criteria were met for MCC in both groups.

End point values	MCC-TT (period 1)	MCC-CRM (period 1)
Number of subjects analysed	121	109
Units: Percentage of subjects
number (confidence interval 95%)
Anti-MCC ≥8 (1/dil) (N=121, 109)	100 (97 to 100)	99.1 (95 to 100)

No statistical analyses for this end point

Secondary: Acceptability of the SPR to Hib (PRP) 1 month Post-Dose 3 of PR5I vaccine administered concomitantly with MCC-TT or MCC-CRM vaccine (V4)

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End point title

Acceptability of the SPR to Hib (PRP) 1 month Post-Dose 3 of PR5I vaccine administered concomitantly with MCC-TT or MCC-CRM vaccine (V4)

End point description

The SPR to Hib (proportion of subjects with anti-polyribosylribitol phosphate (PRP) Ab titre ≥0.15 µg/mL) was determined 1 month Post-Dose 3 of PR5I vaccine administered concomitantly with MCC-TT or MCC-CRM vaccine (V4). Anti-PRP Ab titres were measured by radioimmunoassay (RIA). Analysis was done on the Period 1 Per Protocol Set (PPS), i.e., all randomised subjects excluding those with protocol deviation which could interfere with the immunogenicity evaluation. Acceptability of the SPR to Hib (based on anti-PRP Ab titre ≥0.15 µg/mL) analysis was based on the 2-sided 95% CI for single group proportion, calculated using the exact binomial method for binary variables as defined by D. Collet. If the lower bound of the 2-sided 95% CI was greater than 80% (i.e., the prespecified acceptability threshold), the SPR to Hib was considered as acceptable for the combined vaccine groups. Acceptability criterion was met.

End point type

Secondary

End point timeframe

1 month Post-Dose 3 of PR5I vaccine administered concomitantly with MCC-TT or MCC-CRM vaccine (V4).

End point values	Combined vaccine groups
Number of subjects analysed	175
Units: Percentage of subjects
number (confidence interval 95%)
Anti-PRP ≥0.15 µg/mL (N=175)	98.9 (95.9 to 99.9)

No statistical analyses for this end point

Secondary: Proportion of subjects with anti-MCC Ab titres ≥8 (1/dil) and ≥128 (1/dil) 1 month Post-Dose 1 and 2 of MCC-TT or MCC-CRM vaccine administered concomitantly with PR5I vaccine (V3 and V4)

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End point title

Proportion of subjects with anti-MCC Ab titres ≥8 (1/dil) and ≥128 (1/dil) 1 month Post-Dose 1 and 2 of MCC-TT or MCC-CRM vaccine administered concomitantly with PR5I vaccine (V3 and V4)

End point description

Proportion of subjects with anti-MCC Ab titres ≥8 (1/dil) and ≥128 (1/dil) was determined 1 month Post-Dose 1 and 2 of MCC-TT or MCC-CRM vaccine administered concomitantly with PR5I vaccine (V3 and V4). Anti-MCC Ab titres were measured by rSBA. Analysis was done on the Period 1 Per Protocol Set (PPS), i.e., all randomised subjects excluding those with protocol deviation which could interfere with the immunogenicity evaluation. Note: (N=***, ***) represents the number of assessed subjects in the "MCC-TT" and "MCC-CRM" groups, respectively.

End point type

Secondary

End point timeframe

1 month Post-Dose 1 and 2 of MCC-TT or MCC-CRM vaccine administered concomitantly with PR5I vaccine (V3 and V4).

End point values	MCC-TT (period 1)	MCC-CRM (period 1)
Number of subjects analysed	121	109
Units: Percentage of subjects
number (confidence interval 95%)
Post-dose 1 anti-MCC ≥8 (1/dil) (N=102, 84)	100 (96.4 to 100)	96.4 (89.9 to 99.3)
Post-dose 1 anti-MCC ≥128 (1/dil) (N=102, 84)	98 (93.1 to 99.8)	84.5 (75 to 91.5)
Post-dose 2 anti-MCC ≥8 (1/dil) (N=121, 109)	100 (97 to 100)	99.1 (95 to 100)
Post-dose 2 anti-MCC ≥128 (1/dil) (N=121, 109)	99.2 (95.5 to 100)	99.1 (95 to 100)

No statistical analyses for this end point

Secondary: Geometric Mean Titres (GMTs) for MCC 1 month Post-Dose 1 and 2 of MCC-TT or MCC-CRM vaccine administered concomitantly with PR5I vaccine (V3 and V4)

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End point title

Geometric Mean Titres (GMTs) for MCC 1 month Post-Dose 1 and 2 of MCC-TT or MCC-CRM vaccine administered concomitantly with PR5I vaccine (V3 and V4)

End point description

Anti-MCC Ab titres were measured by rSBA 1 month Post-Dose 1 and 2 of MCC-TT or MCC-CRM vaccine administered concomitantly with PR5I vaccine (V3 and V4). Ab titres are expressed in 1/dil. Analysis was done on the Period 1 Per Protocol Set (PPS), i.e., all randomised subjects excluding those with protocol deviation which could interfere with the immunogenicity evaluation. Note: (N=***, ***) represents the number of assessed subjects in the "MCC-TT" and "MCC-CRM" groups, respectively.

End point type

Secondary

End point timeframe

1 month Post-Dose 1 and 2 of MCC-TT or MCC-CRM vaccine administered concomitantly with PR5I vaccine (V3 and V4).

End point values	MCC-TT (period 1)	MCC-CRM (period 1)
Number of subjects analysed	121	109
Units: Titres
geometric mean (confidence interval 95%)
Post-Dose 1 anti-MCC GMT (N=102, 84)	1353 (1058.4 to 1729.6)	285 (201.5 to 403.1)
Post-Dose 2 anti-MCC GMT (N=121, 109)	2024.7 (1689.8 to 2425.9)	1077.4 (847.5 to 1369.8)

No statistical analyses for this end point

Secondary: Ab response rates for all PR5I antigens 1 month Post-Dose 3 of PR5I vaccine administered concomitantly with MCC-TT or MCC-CRM vaccine (V4)

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End point title

Ab response rates for all PR5I antigens 1 month Post-Dose 3 of PR5I vaccine administered concomitantly with MCC-TT or MCC-CRM vaccine (V4)

End point description

% of subjects with an Ab titre ≥0.15 µg/mL for Hib (PRP), ≥10 mIU/mL for Hepatitis B (HBsAg), ≥0.01 & ≥0.1 IU/mL for Diphtheria & Tetanus, ≥8 (1/dil) for Poliovirus types 1, 2 & 3, and % of pertussis seroresponder subjects (Pertussis toxoid (PT), Filamentous haemagglutinin (FHA), Fimbriae types 2 & 3 (FIM) & Pertactin (PRN)) 1 month Post-Dose 3 of PR5I administered concomitantly with MCC vaccines (V4). Seroresponse was defined: (1) If pre-vaccination Ab concentration (cc) was <LLOQ (lower limit of quantification), post-vaccination Ab cc was to be ≥LLOQ; (2) If pre-vaccination Ab cc was ≥LLOQ, post-vaccination Ab cc was to be ≥pre-immunisation levels. Ab titres were measured by RIA for PRP, enhanced Chemiluminescence assay (ECi) for HBsAg, micrometabolic inhibition test (MIT) for Diphtheria & Poliovirus, and Enzyme-Linked Immunosorbent Assay (ELISA) for Tetanus, PT, FHA, FIM & PRN. Analysis was done on the Period 1 PPS. Note: (N=***, ***) represents the number of assessed subjects.

End point type

Secondary

End point timeframe

1 month Post-Dose 3 of PR5I vaccine administered concomitantly with MCC-TT or MCC-CRM vaccine (V4).

End point values	MCC-TT (period 1)	MCC-CRM (period 1)
Number of subjects analysed	125	105
Units: Percentage of subjects
number (confidence interval 95%)
Anti-PRP ≥0.15 µg/mL (N=93, 82)	97.8 (92.4 to 99.7)	100 (95.6 to 100)
Anti-HBsAg ≥10 mIU/mL (N=93, 82)	96.8 (90.9 to 99.3)	96.3 (89.7 to 99.2)
Anti-Diphtheria ≥0.01 IU/mL (N=125, 104)	100 (97.1 to 100)	100 (96.5 to 100)
Anti-Diphtheria ≥0.1 IU/mL (N=125, 104)	68 (59.1 to 76.1)	74 (64.5 to 82.1)
Anti-Tetanus ≥0.01 IU/mL (N=122, 105)	100 (97 to 100)	100 (96.5 to 100)
Anti-Tetanus ≥0.1 IU/mL (N=122, 105)	100 (97 to 100)	100 (96.5 to 100)
Anti-PT seroresponse (N=100, 75)	99 (94.6 to 100)	100 (95.2 to 100)
Anti-FHA seroresponse (N=100, 74)	91 (83.6 to 95.8)	90.5 (81.5 to 96.1)
Anti-PRN seroresponse (N=100, 73)	95 (88.7 to 98.4)	90.4 (81.2 to 96.1)
Anti-FIM seroresponse (N=100, 75)	96 (90.1 to 98.9)	96 (88.8 to 99.2)
Anti-Polio 1 ≥8 (1/dil) (N=114, 95)	100 (96.8 to 100)	100 (96.2 to 100)
Anti-Polio 2 ≥8 (1/dil) (N=106, 89)	100 (96.6 to 100)	100 (95.9 to 100)
Anti-Polio 3 ≥8 (1/dil) (N=90, 74)	100 (96 to 100)	100 (95.1 to 100)

No statistical analyses for this end point

Secondary: Geometric Mean Titres (GMTs) for all PR5I antigens 1 month Post-Dose 3 of PR5I vaccine administered concomitantly with MCC-TT or MCC-CRM vaccine (V4)

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End point title

Geometric Mean Titres (GMTs) for all PR5I antigens 1 month Post-Dose 3 of PR5I vaccine administered concomitantly with MCC-TT or MCC-CRM vaccine (V4)

End point description

Ab titres were measured by RIA for Hib (PRP), ECi for HBsAg, MIT for Diphtheria & Poliovirus, and ELISA for Tetanus, PT, FHA, FIM & PRN 1 month Post-Dose 3 of PR5I vaccine administered concomitantly with MCC-TT or MCC-CRM vaccine (V4). Ab titres are expressed in µg/mL for Hib (PRP), mIU/mL for HBsAg, IU/mL for Diphtheria & Tetanus, ELISA units (EU)/mL for Pertussis (PT, FHA, FIM & PRN), and 1/dil for Poliovirus types 1, 2 & 3. Analysis was done on the Period 1 Per Protocol Set (PPS), i.e., all randomised subjects excluding those with protocol deviation which could interfere with the immunogenicity evaluation. Note: (N=***, ***) represents the number of assessed subjects in the "MCC-TT" and "MCC-CRM" groups, respectively.

End point type

Secondary

End point timeframe

1 month Post-Dose 3 of PR5I vaccine administered concomitantly with MCC-TT or MCC-CRM vaccine (V4).

End point values	MCC-TT (period 1)	MCC-CRM (period 1)
Number of subjects analysed	125	105
Units: Titres
geometric mean (confidence interval 95%)
Anti-PRP GMT (N=93, 82)	6.44 (4.7 to 8.83)	8.21 (6.08 to 11.09)
Anti-HBsAg GMT (N=93, 82)	195.1 (150.7 to 252.7)	247.7 (186.3 to 329.3)
Anti-Diphtheria GMT (N=125, 104)	0.198 (0.165 to 0.237)	0.22 (0.181 to 0.268)
Anti-Tetanus GMT (N=122, 105)	1.03 (0.9 to 1.17)	0.95 (0.82 to 1.1)
Anti-PT GMT (N=112, 89)	131.5 (117.2 to 147.6)	133.3 (118.3 to 150.2)
Anti-FHA GMT (N=112, 88)	50.4 (44.8 to 56.6)	50.1 (43.7 to 57.4)
Anti-PRN GMT (N=112, 87)	90.4 (73.2 to 111.7)	106.8 (83.7 to 136.3)
Anti-FIM GMT (N=112, 89)	401.7 (339.4 to 475.5)	441.7 (363.2 to 537.2)
Anti-Polio 1 GMT (N=114, 95)	214 (164.9 to 277.7)	257.9 (193.8 to 343.1)
Anti-Polio 2 GMT (N=106, 89)	385.2 (288.2 to 514.9)	400.6 (290.6 to 552.3)
Anti-Polio 3 GMT (N=90, 74)	502.2 (370.2 to 681.4)	405.1 (284.9 to 576)

No statistical analyses for this end point

Secondary: Proportion of subjects with anti-MCC Ab titres ≥8 (1/dil) and ≥128 (1/dil) before (Pre, V5) and 1 month after (Post, V6) Hib-MCC vaccine dose

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End point title

Proportion of subjects with anti-MCC Ab titres ≥8 (1/dil) and ≥128 (1/dil) before (Pre, V5) and 1 month after (Post, V6) Hib-MCC vaccine dose

End point description

Proportion of subjects with anti-MCC Ab titres ≥8 (1/dil) and ≥128 (1/dil) determined before (Pre Hib-MCC dose, V5) and 1 month after Hib-MCC vaccine toddler dose administration (Post Hib-MCC dose, V6). Anti-MCC Ab titres were measured by rSBA. Analysis was done on the Period 2 Per Protocol Set (PPS), i.e., all randomised subjects vaccinated in period 2, excluding those with protocol deviation which could interfere with the immunogenicity evaluation. Note: (N=***, ***) represents the number of assessed subjects in the "MCC-TT" and "MCC-CRM" groups, respectively.

End point type

Secondary

End point timeframe

Before (Pre Hib-MCC dose, V5) and 1 month after Hib-MCC vaccine toddler dose administration (Post Hib-MCC dose, V6).

End point values	MCC-TT (period 2)	MCC-CRM (period 2)
Number of subjects analysed	109	110
Units: Percentage of subjects
number (confidence interval 95%)
Pre Hib-MCC anti-MCC ≥8 (1/dil) (N=89, 94)	83.1 (73.7 to 90.2)	40.4 (30.4 to 51)
Pre Hib-MCC anti-MCC ≥128 (1/dil) (N=89, 94)	40.4 (30.2 to 51.4)	16 (9.2 to 25)
Post Hib-MCC anti-MCC ≥8 (1/dil) (N=109, 110)	100 (96.7 to 100)	97.3 (92.2 to 99.4)
Post Hib-MCC anti-MCC ≥128 (1/dil) (N=109, 110)	99.1 (95 to 100)	95.5 (89.7 to 98.5)

No statistical analyses for this end point

Secondary: Geometric Mean Titres (GMTs) for MCC before (Pre, V5) and 1 month after (Post, V6) Hib-MCC vaccine dose

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End point title

Geometric Mean Titres (GMTs) for MCC before (Pre, V5) and 1 month after (Post, V6) Hib-MCC vaccine dose

End point description

Anti-MCC Ab titres were measured by rSBA before (Pre Hib-MCC dose, V5) and 1 month after Hib-MCC vaccine toddler dose administration (Post Hib-MCC dose, V6). Ab titres are expressed in 1/dil. Analysis was done on the Period 2 Per Protocol Set (PPS), i.e., all randomised subjects vaccinated in period 2, excluding those with protocol deviation which could interfere with the immunogenicity evaluation. Note: (N=***, ***) represents the number of assessed subjects in the "MCC-TT" and "MCC-CRM" groups, respectively.

End point type

Secondary

End point timeframe

Before (Pre Hib-MCC dose, V5) and 1 month after Hib-MCC vaccine toddler dose administration (Post Hib-MCC dose, V6).

End point values	MCC-TT (period 2)	MCC-CRM (period 2)
Number of subjects analysed	109	110
Units: Titres
geometric mean (confidence interval 95%)
Pre Hib-MCC dose anti-MCC GMT (N=89, 94)	50.3 (34.4 to 73.4)	8.7 (5.9 to 12.9)
Post Hib-MCC dose anti-MCC GMT (N=109, 110)	3257.9 (2597.4 to 4086.3)	580.8 (432.7 to 779.5)

No statistical analyses for this end point

Secondary: Proportion of subjects with anti-PRP Ab titres ≥0.15 µg/mL and ≥1.0 µg/mL before (Pre, V5) and 1 month after (Post, V6) Hib-MCC vaccine dose

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End point title

Proportion of subjects with anti-PRP Ab titres ≥0.15 µg/mL and ≥1.0 µg/mL before (Pre, V5) and 1 month after (Post, V6) Hib-MCC vaccine dose

End point description

Proportion of subjects with anti-PRP Ab titres ≥0.15 µg/mL and ≥1.0 µg/mL determined before (Pre Hib-MCC dose, V5) and 1 month after Hib-MCC vaccine toddler dose administration (Post Hib-MCC dose, V6). Anti-PRP Ab titres were measured by radioimmunoassay (RIA). Analysis was done on the Period 2 Per Protocol Set (PPS), i.e., all randomised subjects vaccinated in period 2, excluding those with protocol deviation which could interfere with the immunogenicity evaluation. Note: (N=***, ***) represents the number of assessed subjects in the "MCC-TT" and "MCC-CRM" groups, respectively.

End point type

Secondary

End point timeframe

Before (Pre Hib-MCC dose, V5) and 1 month after Hib-MCC vaccine toddler dose administration (Post Hib-MCC dose, V6).

End point values	MCC-TT (period 2)	MCC-CRM (period 2)
Number of subjects analysed	110	106
Units: Percentage of subjects
number (confidence interval 95%)
Pre Hib-MCC anti-PRP ≥0.15 µg/mL (N=82, 87)	93.9 (86.3 to 98)	95.4 (88.6 to 98.7)
Pre Hib-MCC anti-PRP ≥1.0 µg/mL (N=82, 87)	54.9 (43.5 to 65.9)	56.3 (45.3 to 66.9)
Post Hib-MCC anti-PRP ≥0.15 µg/mL (N=110, 106)	100 (96.7 to 100)	100 (96.6 to 100)
Post Hib-MCC anti-PRP ≥1.0 µg/mL (N=110, 106)	99.1 (95 to 100)	100 (96.6 to 100)

No statistical analyses for this end point

Secondary: Geometric Mean Titres (GMTs) for Hib (PRP) before (Pre, V5) and 1 month after (Post, V6) Hib-MCC vaccine dose

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End point title

Geometric Mean Titres (GMTs) for Hib (PRP) before (Pre, V5) and 1 month after (Post, V6) Hib-MCC vaccine dose

End point description

Anti-PRP Ab titres were measured by RIA before (Pre Hib-MCC dose) and 1 month after Hib-MCC vaccine toddler dose administration (Post Hib-MCC dose). Ab titres are expressed in µg/mL. Analysis was done on the Period 2 Per Protocol Set (PPS), i.e., all randomised subjects vaccinated in period 2, excluding those with protocol deviation which could interfere with the immunogenicity evaluation. Note: (N=***, ***) represents the number of assessed subjects in the "MCC-TT" and "MCC-CRM" groups, respectively.

End point type

Secondary

End point timeframe

Before (Pre Hib-MCC dose) and 1 month after Hib-MCC toddler dose administration (Post Hib-MCC dose).

End point values	MCC-TT (period 2)	MCC-CRM (period 2)
Number of subjects analysed	110	106
Units: Titres
geometric mean (confidence interval 95%)
Pre Hib-MCC dose anti-PRP GMT (N=82, 87)	1.09 (0.81 to 1.45)	1.18 (0.9 to 1.55)
Post Hib-MCC dose anti-PRP GMT (N=110, 106)	100.19 (81.05 to 123.86)	121 (101.11 to 144.8)

No statistical analyses for this end point

Secondary: Global summary of safety from D1 to D15 after any infant dose vaccination (3 doses of PR5I vaccine and 2 doses of MCC-TT or MCC-CRM vaccine)

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End point title

Global summary of safety from D1 to D15 after any infant dose vaccination (3 doses of PR5I vaccine and 2 doses of MCC-TT or MCC-CRM vaccine)

End point description

Adverse events (AEs) were recorded as follows: 1/ From D1 to D5 after each vaccination: # temperature (at least 1 ≥38.0°C), # solicited injection-site adverse reactions (ISRs: erythema, pain, and swelling) by injection-site (PR5I or MCC vaccine), and # solicited systemic AEs (crying, decreased appetite, irritability, pyrexia, somnolence, and vomiting). 2/ From D1 to D15 after each vaccination: unsolicited ISRs (including erythema, pain, and swelling from D6 to D15) by injection-site (PR5I or MCC vaccine), and # unsolicited systemic AEs. AEs at injection sites were always considered as related to vaccine (ISRs). The investigator had to assess whether systemic AEs were vaccine-related systemic AEs or not. Analysis was done on the Period 1 Safety Set, i.e., all subjects who received at least 1 study vaccine during period 1 and who had safety follow-up data in period 1. Percentages of subjects reporting AEs that occurred after any infant dose vaccination are presented herafter.

End point type

Secondary

End point timeframe

From Day 1 (D1) to D15 after any infant dose vaccination (3 doses of PR5I vaccine and 2 doses of MCC-TT or MCC-CRM vaccine).

End point values	MCC-TT (period 1)	MCC-CRM (period 1)
Number of subjects analysed	142	142
Units: Percentage of subjects
number (confidence interval 95%)
At least 1 AE (D1-D15)	98.6 (95 to 99.8)	97.2 (92.9 to 99.2)
At least 1 vaccine-related AE (D1-D15)	98.6 (95 to 99.8)	96.5 (92 to 98.8)
At least 1 ISR at PR5I site (D1-D15)	88.7 (82.3 to 93.4)	87.3 (80.7 to 92.3)
At least 1 solicited ISR at PR5I site (D1-D5)	88.7 (82.3 to 93.4)	87.3 (80.7 to 92.3)
At least 1 unsolicited ISR at PR5I site (D1-D15)	6.3 (2.9 to 11.7)	11.3 (6.6 to 17.7)
At least 1 ISR at MCC site (D1-D15)	72.5 (64.4 to 79.7)	66.2 (57.8 to 73.9)
At least 1 solicited ISR at MCC site (D1-D5)	72.5 (64.4 to 79.7)	65.5 (57.1 to 73.3)
At least 1 unsolicited ISR at MCC site (D1-D15)	2.8 (0.8 to 7.1)	2.8 (0.8 to 7.1)
At least 1 systemic AE (D1-D15)	98.6 (95 to 99.8)	94.4 (89.2 to 97.5)
At least 1 vaccine-related systemic AE (D1-D15)	97.9 (94 to 99.6)	93.7 (88.3 to 97.1)
At least 1 solicited systemic AE (D1-D5)	97.2 (92.9 to 99.2)	93 (87.4 to 99.6)

No statistical analyses for this end point

Secondary: Percentage of subjects reporting ISRs at PR5I injection-site from D1 to D5 (solicited) or D1 to D15 (unsolicited) after any infant dose vaccination (3 doses of PR5I vaccine)

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End point title

Percentage of subjects reporting ISRs at PR5I injection-site from D1 to D5 (solicited) or D1 to D15 (unsolicited) after any infant dose vaccination (3 doses of PR5I vaccine)

End point description

ISRs occurring after any infant dose of PR5I vaccine (3 doses) were recorded as follows: # From D1 to D5 after each vaccination: solicited ISRs, i.e., erythema, pain, and swelling at PR5I injection-site. # From D1 to D15 after each vaccination: unsolicited ISRs (including erythema, pain, and swelling from D6 to D15) at PR5I injection-site. AEs at injection-site were always considered as related to vaccine (ISRs). The percentage of subjects presenting at least once the following ISRs that occurred after any infant dose vaccination is reported hereafter. Analysis was done on the Period 1 Safety Set, i.e., all subjects who received at least 1 study vaccine during period 1 and who had safety follow-up data in period 1.

End point type

Secondary

End point timeframe

# Solicited ISRs: from Day 1 (D1) to D5 after any infant dose of PR5I vaccine (3 doses). # Unsolicited ISRs: from Day 1 (D1) to D15 after any infant dose of PR5I vaccine (3 doses).

End point values	MCC-TT (period 1)	MCC-CRM (period 1)
Number of subjects analysed	142	142
Units: Percentage of subjects
number (not applicable)
Solicited injection-site erythema (D1-D5)	71.1	64.8
Solicited injection-site pain (D1-D5)	63.4	66.2
Solicited injection-site swelling (D1-D5)	51.4	47.2
Unsolicited injection-site bruising (D1-D15)	1.4	4.2
Unsolicited injection-site dermatitis (D1-D15)	0	0.7
Unsolicited injection-site erythema (D6-D15)	0	0.7
Unsolicited injection-site induration (D1-D15)	1.4	0.7
Unsolicited injection-site mass (D1-D15)	3.5	2.1
Unsolicited injection-site pain (D6-D15)	0	0.7
Unsolicited injection-site rash (D1-D15)	1.4	0.7
Unsolicited injection-site warmth (D1-D15)	0	2.1

No statistical analyses for this end point

Secondary: Percentage of subjects reporting ISRs at MCC-TT or MCC-CRM injection-site from D1 to D5 (solicited) or D1 to D15 (unsolicited) after any infant dose vaccination (2 doses of MCC-TT or MCC-CRM vaccine)

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End point title

Percentage of subjects reporting ISRs at MCC-TT or MCC-CRM injection-site from D1 to D5 (solicited) or D1 to D15 (unsolicited) after any infant dose vaccination (2 doses of MCC-TT or MCC-CRM vaccine)

End point description

ISRs occurring after any infant dose of MCC-TT or MCC-CRM vaccine (2 doses) were recorded as follows: # From D1 to D5: solicited ISRs, i.e., erythema, pain, and swelling at MCC injection-site. # From D1 to D15: unsolicited ISRs (including erythema, pain, and swelling from D6 to D15) at MCC injection-site. AEs at injection-site were always considered as related to vaccine (ISRs). The percentage of subjects presenting at least once the following ISRs that occurred after any infant dose vaccination is reported hereafter. Analysis was done on the Period 1 Safety Set, i.e., all subjects who received at least 1 study vaccine during period 1 and who had safety follow-up data in period 1.

End point type

Secondary

End point timeframe

# Solicited ISRs: from Day 1 (D1) to D5 after any infant dose of MCC-TT or MCC-CRM vaccine (2 doses). # Unsolicited ISRs: from Day 1 (D1) to D15 after any infant dose of MCC-TT or MCC-CRM vaccine (2 doses).

End point values	MCC-TT (period 1)	MCC-CRM (period 1)
Number of subjects analysed	142	142
Units: Percentage of subjects
number (not applicable)
Solicited injection-site erythema (D1-D5)	56.3	45.8
Solicited injection-site pain (D1-D5)	41.5	45.8
Solicited injection-site swelling (D1-D5)	35.9	28.2
Unsolicited injection-site bruising (D1-D15)	1.4	2.1
Unsolicited injection-site induration (D1-D15)	0.7	0
Unsolicited injection-site rash (D1-D15)	0.7	0
Unsolicited injection-site warmth (D1-D15)	0	0.7

No statistical analyses for this end point

Secondary: Percentage of subjects reporting solicited systemic adverse events (AEs) from D1 to D5 after any infant dose vaccination (3 doses of PR5I vaccine and 2 doses of MCC-TT or MCC-CRM vaccine)

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End point title

Percentage of subjects reporting solicited systemic adverse events (AEs) from D1 to D5 after any infant dose vaccination (3 doses of PR5I vaccine and 2 doses of MCC-TT or MCC-CRM vaccine)

End point description

Solicited systemic AEs (crying, decreased appetite, irritability, pyrexia, somnolence, and vomiting) were recorded from D1 to D5 after each vaccination. The investigator had to assess whether systemic AEs were vaccine-related systemic AEs or not. The percentage of subjects presenting at least once the following solicited systemic AEs (vaccine-related or not) that occurred after any infant dose vaccination is presented herafter. Analysis was done on the Period 1 Safety Set, i.e., all subjects who received at least 1 study vaccine during period 1 and who had safety follow-up data in period 1.

End point type

Secondary

End point timeframe

From Day 1 (D1) to D5 after any infant dose vaccination (3 doses of PR5I vaccine and 2 doses of MCC-TT or MCC-CRM vaccine).

End point values	MCC-TT (period 1)	MCC-CRM (period 1)
Number of subjects analysed	142	142
Units: Percentage of subjects
number (not applicable)
Crying (D1-D5)	85.9	81
Decreased appetite (D1-D5)	63.4	64.8
Irritability (D1-D5)	88	81
Pyrexia (D1-D5)	11.3	10.6
Somnolence (D1-D5)	81.7	78.9
Vomiting (D1-D5)	40.1	49.3

No statistical analyses for this end point

Secondary: Percentage of subjects reporting temperature ≥38.0°C, >38.5°C & >39.5°C from D1 to D5 after any infant dose vaccination (3 doses of PR5I vaccine and 2 doses of MCC-TT or MCC-CRM vaccine)

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End point title

Percentage of subjects reporting temperature ≥38.0°C, >38.5°C & >39.5°C from D1 to D5 after any infant dose vaccination (3 doses of PR5I vaccine and 2 doses of MCC-TT or MCC-CRM vaccine)

End point description

Maximum temperatures recorded with no adjustments to the measurement route were reported from D1 to D5 after any infant dose vaccination (3 doses of PR5I vaccine and 2 doses of MCC-TT or MCC-CRM vaccine). The percentage of subjects presenting at least once temperature ≥38.0°C, >38.5°C, and >39.5°C is presented hereafter. Analysis was done on the Period 1 Safety Set, i.e., all subjects who received at least 1 study vaccine during period 1 and who had safety follow-up data in period 1.

End point type

Secondary

End point timeframe

From Day 1 (D1) to D5 after any infant dose vaccination (3 doses of PR5I vaccine and 2 doses of MCC-TT or MCC-CRM vaccine).

End point values	MCC-TT (period 1)	MCC-CRM (period 1)
Number of subjects analysed	142	142
Units: Percentage of subjects
number (not applicable)
Temperature ≥38.0°C	11.3	10.6
Temperature >38.5°C	1.4	2.1
Temperature >39.5°C	0	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

# From D1 to D15 after each vaccination during Period 1: unsolicited non-serious systemic AEs. # From D1 to D15 after each vaccination: serious AEs (SAEs) and deaths, vaccine-related or not. # Throughout the study: deaths and vaccine-related SAEs.

Adverse event reporting additional description

Analysis of AEs was done on the Period 1 Safety Set, i.e., all subjects who received at least 1 study vaccine during period 1 and who had safety follow-up data in period 1. Unsolicited non-serious systemic AEs (vaccine-related or not) with incidence ≥2% are presented hereafter. 1 subject from the MCC-CRM group reported 2 vaccine-related SAEs.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

16.1

Reporting group title

MCC-TT (period 1)

Reporting group description

# Subjects received 3 doses of PR5I vaccine (DTaP-HB-IPV-Hib) by IM route at 2, 3, & 4 months of age + 2 doses of MCC-TT vaccine (NeisVac-C) by IM route at 3 & 4 months of age + routine vaccination, i.e., PCV-13 vaccine (Prevenar 13) by IM route at 2 & 4 months of age. # Respectively, 71 (50.0%) subjects reported at least 1 unsolicited systemic AE, and 38 (26.8%) subjects reported at least 1 vaccine-related unsolicited systemic AE within 15 days after any infant dose vaccination (3 doses of PR5I vaccine and 2 doses of MCC-TT vaccine).

Reporting group title

MCC-CRM (period 1)

Reporting group description

# Subjects received 3 doses of PR5I vaccine (DTaP-HB-IPV-Hib) by IM route at 2, 3 & 4 months of age + 2 doses of MCC-CRM vaccine (Menjugate) by IM route at 3 & 4 months of age + routine vaccination, i.e., PCV-13 vaccine (Prevenar 13) by IM route at 2 & 4 months of age. # Respectively, 57 (40.1%) subjects reported at least 1 unsolicited systemic AE, and 37 (26.1%) subjects reported at least 1 vaccine-related unsolicited systemic AE within 15 days after any infant dose vaccination (3 doses of PR5I vaccine and 2 doses of MCC-CRM vaccine).

Serious adverse events	MCC-TT (period 1)	MCC-CRM (period 1)
Total subjects affected by serious adverse events
subjects affected / exposed	6 / 142 (4.23%)	4 / 142 (2.82%)
number of deaths (all causes)	0	0
number of deaths resulting from adverse events	0	0
General disorders and administration site conditions
Crying
Additional description: Transient (2 days), severe intensity, occurring concomitantly with abdominal pain in 1 subject.
subjects affected / exposed	0 / 142 (0.00%)	1 / 142 (0.70%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypothermia
subjects affected / exposed	1 / 142 (0.70%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
Additional description: Transient (2 days), severe intensity, occurring concomitantly with crying in 1 subject.
subjects affected / exposed	0 / 142 (0.00%)	1 / 142 (0.70%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Choking
subjects affected / exposed	0 / 142 (0.00%)	1 / 142 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Croup infectious
subjects affected / exposed	1 / 142 (0.70%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis salmonella
subjects affected / exposed	0 / 142 (0.00%)	1 / 142 (0.70%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	0 / 142 (0.00%)	1 / 142 (0.70%)
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	1 / 142 (0.70%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sepsis neonatal
subjects affected / exposed	1 / 142 (0.70%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 142 (0.70%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolism and nutrition disorders
Weight gain poor
subjects affected / exposed	1 / 142 (0.70%)	0 / 142 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 2%

Non-serious adverse events	MCC-TT (period 1)	MCC-CRM (period 1)
Total subjects affected by non serious adverse events
subjects affected / exposed	71 / 142 (50.00%)	57 / 142 (40.14%)
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	0 / 142 (0.00%)	3 / 142 (2.11%)
occurrences all number	0	3
Gastrointestinal disorders
Constipation
subjects affected / exposed	4 / 142 (2.82%)	3 / 142 (2.11%)
occurrences all number	4	3
Diarrhoea
subjects affected / exposed	11 / 142 (7.75%)	8 / 142 (5.63%)
occurrences all number	11	8
Teething
subjects affected / exposed	7 / 142 (4.93%)	1 / 142 (0.70%)
occurrences all number	7	1
Vomiting
subjects affected / exposed	3 / 142 (2.11%)	3 / 142 (2.11%)
occurrences all number	3	3
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	12 / 142 (8.45%)	6 / 142 (4.23%)
occurrences all number	12	6
Nasal congestion
subjects affected / exposed	4 / 142 (2.82%)	2 / 142 (1.41%)
occurrences all number	4	2
Rhinorrhoea
subjects affected / exposed	3 / 142 (2.11%)	4 / 142 (2.82%)
occurrences all number	3	4
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	8 / 142 (5.63%)	6 / 142 (4.23%)
occurrences all number	8	6
Psychiatric disorders
Insomnia
subjects affected / exposed	4 / 142 (2.82%)	1 / 142 (0.70%)
occurrences all number	4	1
Infections and infestations
Nasopharyngitis
subjects affected / exposed	11 / 142 (7.75%)	12 / 142 (8.45%)
occurrences all number	11	12
Rhinitis
subjects affected / exposed	8 / 142 (5.63%)	6 / 142 (4.23%)
occurrences all number	8	6

More information

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Were there any global substantial amendments to the protocol? No

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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Acceptability of the seroprotection rate (SPR) to MCC 1 month Post-Dose 2 of MCC-TT or MCC-CRM vaccine administered concomitantly with PR5I vaccine (V4)

Primary: Acceptability of the seroprotection rate (SPR) to MCC 1 month Post-Dose 2 of MCC-TT or MCC-CRM vaccine administered concomitantly with PR5I vaccine (V4)

Secondary: Acceptability of the SPR to Hib (PRP) 1 month Post-Dose 3 of PR5I vaccine administered concomitantly with MCC-TT or MCC-CRM vaccine (V4)

Secondary: Acceptability of the SPR to Hib (PRP) 1 month Post-Dose 3 of PR5I vaccine administered concomitantly with MCC-TT or MCC-CRM vaccine (V4)

Secondary: Proportion of subjects with anti-MCC Ab titres ≥8 (1/dil) and ≥128 (1/dil) 1 month Post-Dose 1 and 2 of MCC-TT or MCC-CRM vaccine administered concomitantly with PR5I vaccine (V3 and V4)

Secondary: Proportion of subjects with anti-MCC Ab titres ≥8 (1/dil) and ≥128 (1/dil) 1 month Post-Dose 1 and 2 of MCC-TT or MCC-CRM vaccine administered concomitantly with PR5I vaccine (V3 and V4)

Secondary: Geometric Mean Titres (GMTs) for MCC 1 month Post-Dose 1 and 2 of MCC-TT or MCC-CRM vaccine administered concomitantly with PR5I vaccine (V3 and V4)

Secondary: Geometric Mean Titres (GMTs) for MCC 1 month Post-Dose 1 and 2 of MCC-TT or MCC-CRM vaccine administered concomitantly with PR5I vaccine (V3 and V4)

Secondary: Ab response rates for all PR5I antigens 1 month Post-Dose 3 of PR5I vaccine administered concomitantly with MCC-TT or MCC-CRM vaccine (V4)

Secondary: Ab response rates for all PR5I antigens 1 month Post-Dose 3 of PR5I vaccine administered concomitantly with MCC-TT or MCC-CRM vaccine (V4)

Secondary: Geometric Mean Titres (GMTs) for all PR5I antigens 1 month Post-Dose 3 of PR5I vaccine administered concomitantly with MCC-TT or MCC-CRM vaccine (V4)

Secondary: Geometric Mean Titres (GMTs) for all PR5I antigens 1 month Post-Dose 3 of PR5I vaccine administered concomitantly with MCC-TT or MCC-CRM vaccine (V4)

Secondary: Proportion of subjects with anti-MCC Ab titres ≥8 (1/dil) and ≥128 (1/dil) before (Pre, V5) and 1 month after (Post, V6) Hib-MCC vaccine dose

Secondary: Proportion of subjects with anti-MCC Ab titres ≥8 (1/dil) and ≥128 (1/dil) before (Pre, V5) and 1 month after (Post, V6) Hib-MCC vaccine dose

Secondary: Geometric Mean Titres (GMTs) for MCC before (Pre, V5) and 1 month after (Post, V6) Hib-MCC vaccine dose

Secondary: Geometric Mean Titres (GMTs) for MCC before (Pre, V5) and 1 month after (Post, V6) Hib-MCC vaccine dose

Secondary: Proportion of subjects with anti-PRP Ab titres ≥0.15 µg/mL and ≥1.0 µg/mL before (Pre, V5) and 1 month after (Post, V6) Hib-MCC vaccine dose

Secondary: Proportion of subjects with anti-PRP Ab titres ≥0.15 µg/mL and ≥1.0 µg/mL before (Pre, V5) and 1 month after (Post, V6) Hib-MCC vaccine dose

Secondary: Geometric Mean Titres (GMTs) for Hib (PRP) before (Pre, V5) and 1 month after (Post, V6) Hib-MCC vaccine dose

Secondary: Geometric Mean Titres (GMTs) for Hib (PRP) before (Pre, V5) and 1 month after (Post, V6) Hib-MCC vaccine dose

Secondary: Global summary of safety from D1 to D15 after any infant dose vaccination (3 doses of PR5I vaccine and 2 doses of MCC-TT or MCC-CRM vaccine)

Secondary: Global summary of safety from D1 to D15 after any infant dose vaccination (3 doses of PR5I vaccine and 2 doses of MCC-TT or MCC-CRM vaccine)

Secondary: Percentage of subjects reporting ISRs at PR5I injection-site from D1 to D5 (solicited) or D1 to D15 (unsolicited) after any infant dose vaccination (3 doses of PR5I vaccine)

Secondary: Percentage of subjects reporting ISRs at PR5I injection-site from D1 to D5 (solicited) or D1 to D15 (unsolicited) after any infant dose vaccination (3 doses of PR5I vaccine)

Secondary: Percentage of subjects reporting ISRs at MCC-TT or MCC-CRM injection-site from D1 to D5 (solicited) or D1 to D15 (unsolicited) after any infant dose vaccination (2 doses of MCC-TT or MCC-CRM vaccine)

Secondary: Percentage of subjects reporting ISRs at MCC-TT or MCC-CRM injection-site from D1 to D5 (solicited) or D1 to D15 (unsolicited) after any infant dose vaccination (2 doses of MCC-TT or MCC-CRM vaccine)

Secondary: Percentage of subjects reporting solicited systemic adverse events (AEs) from D1 to D5 after any infant dose vaccination (3 doses of PR5I vaccine and 2 doses of MCC-TT or MCC-CRM vaccine)

Secondary: Percentage of subjects reporting solicited systemic adverse events (AEs) from D1 to D5 after any infant dose vaccination (3 doses of PR5I vaccine and 2 doses of MCC-TT or MCC-CRM vaccine)

Secondary: Percentage of subjects reporting temperature ≥38.0°C, >38.5°C & >39.5°C from D1 to D5 after any infant dose vaccination (3 doses of PR5I vaccine and 2 doses of MCC-TT or MCC-CRM vaccine)

Secondary: Percentage of subjects reporting temperature ≥38.0°C, >38.5°C & >39.5°C from D1 to D5 after any infant dose vaccination (3 doses of PR5I vaccine and 2 doses of MCC-TT or MCC-CRM vaccine)

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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