Clinical Trial Results:
A Phase 3b, Open-Label, Randomized, Parallel-Group, Multi-Center Study to Evaluate the Safety of Novartis MenACWY Conjugate Vaccine when Administered with Routine Infant Vaccinations to Healthy Infants

Due to a system error, the data reported in v1 is not correct and has been removed from public view.

Summary
EudraCT number	2014-004537-95
Trial protocol	Outside EU/EEA
Global end of trial date	10 Nov 2011

Results information
Results version number	v2(current)
This version publication date	04 Jun 2016
First version publication date	12 Feb 2015
Other versions	v1 (removed from public view)
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

V59P23

ISRCTN number

US NCT number

NCT00806195

WHO universal trial number (UTN)

Sponsor organisation name

Novartis Vaccines and Diagnostics Inc.

Sponsor organisation address

350 Massachusetts Avenue, Cambridge, United States, 02139-4182

Public contact

Posting Director, Novartis Vaccines and Diagnostics Inc., RegistryContactVaccinesUS@novartis.com

Scientific contact

Posting Director, Novartis Vaccines and Diagnostics Inc., RegistryContactVaccinesUS@novartis.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?

Analysis stage

Final

Date of interim/final analysis

05 Dec 2012

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

10 Nov 2011

Was the trial ended prematurely?

Main objective of the trial

To assess the safety and tolerability of 4 doses of MenACWY through 6 months post-final dose when given concomitantly with routine infant vaccines.

Protection of trial subjects

This clinical study was designed, implemented and reported in accordance with the ICH Harmonized Tripartite Guidelines for Good Clinical Practice (GCP), with applicable local regulations, including the European Directive 2001/20/EC, the US CFR Title 21, and the Japanese Ministry of Health, Labor, and Welfare, Novartis codes on the protection of human rights, and with the ethical principles laid down in the Declaration of Helsinki.

Background therapy

Evidence for comparator

Actual start date of recruitment

05 Dec 2008

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

6 Months

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 3854

Country: Number of subjects enrolled

Peru: 396

Country: Number of subjects enrolled

Guatemala: 1096

Country: Number of subjects enrolled

Taiwan: 795

Country: Number of subjects enrolled

Costa Rica: 1301

Country: Number of subjects enrolled

Panama: 302

Worldwide total number of subjects

7744

EEA total number of subjects

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)

7744

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 centers were located in the US, Taiwan, Costa Rica, Guatemala, Peru and Panama.

Screening details

All subjects enrolled were included in the trial.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

MenACWY-CRM197 + Routine Vaccines (Non-detailed)

Arm description

Infants received one vaccination of MenACWY-CRM197 vaccine at 2, 4, 6 and 12 months of age and one vaccination of routine vaccines (according to the local vaccination schedule) - DTaP: 2, 4, 6, 15 months, IPV: 2, 4, 6, months, Hib: 2, 4, 6, 15 months, Pneumococcal conjugate: 2, 4, 6, 12 months, MMR: 12 months. Routine vaccines given to subjects in these arms will be consistent with the US ACIP recommended vaccines. Non-Detailed - subjects who only provided Serious Adverse Events (SAEs) and medically attended Adverse Events (AEs). Additional vaccines could be included if required according to local guidelines for ex-US subjects, with the exception of all meningococcal vaccines.

Arm type

Experimental

Investigational medicinal product name

Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solution for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

After reconstitution, one dose (0.5 ml) of MenACWY injectable solution was administered by IM at 2, 4, 6 and 12 months of age.

Investigational medicinal product name

DTaP (Diphtheria, Tetanus, Pertussis) Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Vaccines was used according to site practice.

Investigational medicinal product name

Hib (Haemophilus influenza b) Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Vaccine was used according to site practice.

Investigational medicinal product name

IPV (Inactivated Polio Vaccine) Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Vaccine was used according to site practice.

Investigational medicinal product name

Pneumococcal conjugate Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Vaccine was used according to site practice.

Investigational medicinal product name

MMR (Measles, Mumps, and Rubella) Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Vaccine was used according to site practice.

Routine Vaccines (Non-detailed)

Arm description

Infants received one vaccination of routine vaccines (according to the local vaccination schedule) - DTaP: 2, 4, 6, 15 months, IPV: 2, 4, 6 months, Hib: 2, 4, 6, 15 months, Pneumococcal conjugate: 2, 4, 6, 12 months, MMR: 12 months. Routine vaccines given to subjects in these arms will be consistent with the US ACIP recommended vaccines. Non-Detailed - subjects who only provided SAEs and medically attended AEs. Additional vaccines could be included if required according to local guidelines for ex-US subjects, with the exception of all meningococcal vaccines.

Arm type

Active comparator

Investigational medicinal product name

DTaP (Diphtheria, Tetanus, Pertussis) Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Vaccines was used according to site practice.

Investigational medicinal product name

Hib (Haemophilus influenza b) Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Vaccine was used according to site practice.

Investigational medicinal product name

IPV (Inactivated Polio Vaccine) Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Vaccine was used according to site practice.

Investigational medicinal product name

Pneumococcal conjugate Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Vaccine was used according to site practice.

Investigational medicinal product name

MMR (Measles, Mumps, and Rubella) Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Vaccine was used according to site practice.

MenACWY-CRM197 + Routine Vaccines (Detailed)

Arm description

Infants received one vaccination of MenACWY-CRM197 vaccine at 2, 4, 6 and 12 months of age and one vaccination of routine vaccines (according to the local vaccination schedule) - DTaP: 2, 4, 6, 15 months, IPV: 2, 4, 6, months, Hib: 2, 4, 6, 15 months, Pneumococcal conjugate: 2, 4, 6, 12 months, MMR, Varicella, Hepatitis A: 12 months. HBV and rotavirus vaccines should be administered according to ACIP guidelines during the first year of life. Routine vaccines given to subjects in these arms will be consistent with the US ACIP recommended vaccines. Detailed - subjects who provided Reactogenicity and all AEs for 7 days, SAEs and medically attended AEs.

Arm type

Experimental

Investigational medicinal product name

Meningococcal (groups A, C, W, and Y) oligosaccharide diphtheria CRM-197 conjugate vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and solution for solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

After reconstitution, one dose (0.5 ml) of MenACWY injectable solution was administered by IM at 2, 4, 6 and 12 months of age.

Investigational medicinal product name

DTaP (Diphtheria, Tetanus, Pertussis) Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Vaccines was used according to site practice.

Investigational medicinal product name

Hib (Haemophilus influenza b) Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Vaccine was used according to site practice.

Investigational medicinal product name

IPV (Inactivated Polio Vaccine) Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Vaccine was used according to site practice.

Investigational medicinal product name

Pneumococcal conjugate Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Vaccine was used according to site practice.

Investigational medicinal product name

MMR (Measles, Mumps, and Rubella) Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Vaccine was used according to site practice.

Investigational medicinal product name

Varicella Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Vaccine was used according to site practice.

Investigational medicinal product name

Hepatitis A Virus Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Vaccine was used according to site practice.

Routine Vaccines (Detailed)

Arm description

Infants received one vaccination of routine vaccines (according to the local vaccination schedule) - DTaP: 2, 4, 6, 15 months, IPV: 2, 4, 6 months, Hib: 2, 4, 6, 15 months, Pneumococcal conjugate: 2, 4, 6, 12 months, MMR, Varicella, and Hepatitis A: 12 months. HBV and rotavirus vaccines should be administered according to ACIP guidelines during the first year of life. Routine vaccines given to subjects in these arms will be consistent with the US ACIP recommended vaccines. Detailed - subjects who provided Reactogenicity, all AEs for 7 days, SAEs and medically attended AEs.

Arm type

Active comparator

Investigational medicinal product name

DTaP (Diphtheria, Tetanus, Pertussis) Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Vaccines was used according to site practice.

Investigational medicinal product name

Hib (Haemophilus influenza b) Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Vaccine was used according to site practice.

Investigational medicinal product name

IPV (Inactivated Polio Vaccine) Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Vaccine was used according to site practice.

Investigational medicinal product name

Pneumococcal conjugate Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Vaccine was used according to site practice.

Investigational medicinal product name

MMR (Measles, Mumps, and Rubella) Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

Vaccine was used according to site practice.

Investigational medicinal product name

Varicella Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Vaccine was used according to site practice.

Investigational medicinal product name

Hepatitis A Virus Vaccine

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Vaccine was used according to site practice.

Number of subjects in period 1	MenACWY-CRM197 + Routine Vaccines (Non-detailed)	Routine Vaccines (Non-detailed)	MenACWY-CRM197 + Routine Vaccines (Detailed)	Routine Vaccines (Detailed)
Started	4363	1483	1409	489
Completed	3849	1321	1139	383
Not completed	514	162	270	106
Consent withdrawn by subject	119	31	76	35
Death	6	-	1	-
Inappropriate enrollment	-	1	-	-
Adverse event	25	5	11	2
Lost to follow-up	217	66	90	34
Protocol deviation	34	24	26	9
Administrative reason	113	35	66	26

Baseline characteristics

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Reporting group title

MenACWY-CRM197 + Routine Vaccines (Non-detailed)

Reporting group description

Reporting group title

Routine Vaccines (Non-detailed)

Reporting group description

Reporting group title

MenACWY-CRM197 + Routine Vaccines (Detailed)

Reporting group description

Infants received one vaccination of MenACWY-CRM197 vaccine at 2, 4, 6 and 12 months of age and one vaccination of routine vaccines (according to the local vaccination schedule) - DTaP: 2, 4, 6, 15 months, IPV: 2, 4, 6, months, Hib: 2, 4, 6, 15 months, Pneumococcal conjugate: 2, 4, 6, 12 months, MMR, Varicella, Hepatitis A: 12 months. HBV and rotavirus vaccines should be administered according to ACIP guidelines during the first year of life. Routine vaccines given to subjects in these arms will be consistent with the US ACIP recommended vaccines. Detailed - subjects who provided Reactogenicity and all AEs for 7 days, SAEs and medically attended AEs.

Reporting group title

Routine Vaccines (Detailed)

Reporting group description

Infants received one vaccination of routine vaccines (according to the local vaccination schedule) - DTaP: 2, 4, 6, 15 months, IPV: 2, 4, 6 months, Hib: 2, 4, 6, 15 months, Pneumococcal conjugate: 2, 4, 6, 12 months, MMR, Varicella, and Hepatitis A: 12 months. HBV and rotavirus vaccines should be administered according to ACIP guidelines during the first year of life. Routine vaccines given to subjects in these arms will be consistent with the US ACIP recommended vaccines. Detailed - subjects who provided Reactogenicity, all AEs for 7 days, SAEs and medically attended AEs.

Reporting group values	MenACWY-CRM197 + Routine Vaccines (Non-detailed)	Routine Vaccines (Non-detailed)	MenACWY-CRM197 + Routine Vaccines (Detailed)	Routine Vaccines (Detailed)	Total
Number of subjects	4363	1483	1409	489	7744
Age categorical
Units: Subjects
In utero					0
Preterm newborn infants (gestational age < 37 wks)					0
Newborns (0-27 days)					0
Infants and toddlers (28 days-23 months)					0
Children (2-11 years)					0
Adolescents (12-17 years)					0
Adults (18-64 years)					0
From 65-84 years					0
85 years and over					0
Age continuous
Units: days
arithmetic mean (standard deviation)	64.9 ± 7.4	64.7 ± 7.1	65.5 ± 6.5	65.2 ± 6.3	-
Gender categorical
Units: Subjects
Female	2135	703	716	232	3786
Male	2228	780	693	257	3958

End points

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Reporting group title

MenACWY-CRM197 + Routine Vaccines (Non-detailed)

Reporting group description

Reporting group title

Routine Vaccines (Non-detailed)

Reporting group description

Reporting group title

MenACWY-CRM197 + Routine Vaccines (Detailed)

Reporting group description

Infants received one vaccination of MenACWY-CRM197 vaccine at 2, 4, 6 and 12 months of age and one vaccination of routine vaccines (according to the local vaccination schedule) - DTaP: 2, 4, 6, 15 months, IPV: 2, 4, 6, months, Hib: 2, 4, 6, 15 months, Pneumococcal conjugate: 2, 4, 6, 12 months, MMR, Varicella, Hepatitis A: 12 months. HBV and rotavirus vaccines should be administered according to ACIP guidelines during the first year of life. Routine vaccines given to subjects in these arms will be consistent with the US ACIP recommended vaccines. Detailed - subjects who provided Reactogenicity and all AEs for 7 days, SAEs and medically attended AEs.

Reporting group title

Routine Vaccines (Detailed)

Reporting group description

Infants received one vaccination of routine vaccines (according to the local vaccination schedule) - DTaP: 2, 4, 6, 15 months, IPV: 2, 4, 6 months, Hib: 2, 4, 6, 15 months, Pneumococcal conjugate: 2, 4, 6, 12 months, MMR, Varicella, and Hepatitis A: 12 months. HBV and rotavirus vaccines should be administered according to ACIP guidelines during the first year of life. Routine vaccines given to subjects in these arms will be consistent with the US ACIP recommended vaccines. Detailed - subjects who provided Reactogenicity, all AEs for 7 days, SAEs and medically attended AEs.

Subject analysis set title

All enrolled population (ACWY-All)

Subject analysis set type

Intention-to-treat

Subject analysis set description

All subjects who: - whose parents have signed an informed consent, - had undergone screening procedure and were randomized.

Subject analysis set title

Exposed population (ACWY-All)

Subject analysis set type

Intention-to-treat

Subject analysis set description

All enrolled subjects who actually received a study vaccination (MenACWY-CRM197 vaccine and routine vaccination).

Subject analysis set title

Safety population (ACWY-All)

Subject analysis set type

Safety analysis

Subject analysis set description

All subjects enrolled who received MenACWY-CRM197 vaccine and routine vaccination; - had postbaseline safety data reported

Subject analysis set title

Per Protocol safety population (ACWY-All)

Subject analysis set type

Per protocol

Subject analysis set description

All subjects enrolled who received MenACWY-CRM197 vaccine as specified in the protocol and received all routine vaccinations concomitantly, as per-protocol.

Subject analysis set title

All enrolled population (RVAX-All)

Subject analysis set type

Intention-to-treat

Subject analysis set description

All subjects: - whose parents have signed an informed consent, - had undergone screening procedure and were randomized.

Subject analysis set title

Exposed population (RVAX-All)

Subject analysis set type

Intention-to-treat

Subject analysis set description

All enrolled subjects who actually received the routine vaccination.

Subject analysis set title

Safety population (RVAX-All)

Subject analysis set type

Safety analysis

Subject analysis set description

All subjects enrolled who: - had received the routine vaccination - had postbaseline safety data reported

Subject analysis set title

Per Protocol safety population (RVAX-All)

Subject analysis set type

Per protocol

Subject analysis set description

All subjects enrolled who received all routine vaccinations concomitantly, as per-protocol.

Primary: 1. Percentages of Subjects With At Least One Severe Systemic Reaction After Any Vaccination

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End point title

1. Percentages of Subjects With At Least One Severe Systemic Reaction After Any Vaccination ^[1]

End point description

To compare the percentages of subjects who reported at least one severe systemic reaction after any vaccination of MenACWY-CRM197 plus routine vaccines (detailed) group to that observed in the routine vaccines alone (detailed) group administered at 2, 4, 6, and 12 months of age. Detailed - infants who provided reactogenicity and all Adverse Events (AEs) for 7 days, Serious Adverse Events (SAEs) and medically attended AEs.

End point type

Primary

End point timeframe

15 minutes to Day 7 after any vaccination administered at 2, 4, 6 and 12 months of age

Notes
[1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	MenACWY-CRM197 + Routine Vaccines (Detailed)	Routine Vaccines (Detailed)
Number of subjects analysed	1349	461
Units: Percentages of subjects
Subjects With At Least One SevereSystemic Reaction	16	13

Statistical Analysis 1

Statistical analysis description

MenACWY-CRM 197 administered concomitantly with routine vaccines was considered noninferior to routine vaccines alone with respect to severe systemic reactions if the upper limit of the 2-sided 95% CI of the difference (MenACWY-CRM197 vaccine plus routine vaccines group minus routine vaccines only group) in the proportion of subjects experiencing at least one severe systemic reaction during the first 7 days (days 1-7) after any vaccination was <6%.

Comparison groups

Routine Vaccines (Detailed) v MenACWY-CRM197 + Routine Vaccines (Detailed)

Number of subjects included in analysis

1810

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[2]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

Confidence interval

level

95%

sides

2-sided

lower limit

-0.8

upper limit

6.4

Notes
[2] - The null hypothesis associated with the safety objective was that the upper limit of the two-sided 95% CI for this difference in the proportion of subjects experiencing at least one severe systemic reaction during the first 7 days after any vaccination (PMenACWY+Routine Vaccines–PRoutine Vaccines) was ≥ 6%.

Statistical Analysis 2

Statistical analysis description

Comparison groups

MenACWY-CRM197 + Routine Vaccines (Detailed) v Routine Vaccines (Detailed)

Number of subjects included in analysis

1810

Analysis specification

Post-hoc

Analysis type

non-inferiority ^[3]

Method

Grizzle, Starmer, and Koch Model

Parameter type

Mean difference (final values)

Point estimate

-0.1

Confidence interval

level

95%

sides

2-sided

lower limit

-4.9

upper limit

4.7

Notes
[3] - The null hypothesis associated with the safety objective was that the upper limit of the two-sided 95% CI for this difference in the proportion of subjects experiencing at least one severe systemic reaction during the first 7 days after any vaccination (PMenACWY+Routine Vaccines–PRoutine Vaccines) was ≥ 6%.

Secondary: 2. Percentages of Subjects With At Least One Serious Adverse Event During the Entire Study Period

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End point title

2. Percentages of Subjects With At Least One Serious Adverse Event During the Entire Study Period

End point description

To compare the percentages of subjects presenting at least one serious adverse event (SAE) through 6 months postfinal dose in subjects who received MenACWY-CRM197 vaccine concomitantly with routine vaccinations to the percentages of subjects who received routine vaccinations alone.

End point type

Secondary

End point timeframe

Day 1 (2 months of age) to 18 months of age

End point values	Safety population (ACWY-All)	Safety population (RVAX-All)
Number of subjects analysed	5760	1968
Units: Percentages of subjects
Subjects With At Least One Serious Adverse Event	6	6

Statistical Analysis 1

Statistical analysis description

MenACWY-CRM 197 administered concomitantly with routine vaccines was considered non inferior to routine vaccines alone with respect to serious adverse events if the upper limit of the 2-sided 95% CI of the difference (MenACWY vaccine plus routine vaccines group minus routine vaccines only group) of the proportion of subjects experiencing at least one serious adverse event was <5%.

Comparison groups

Safety population (ACWY-All) v Safety population (RVAX-All)

Number of subjects included in analysis

7728

Analysis specification

Pre-specified

Analysis type

non-inferiority ^[4]

Method

Miettinen and Nurminen

Parameter type

Mean difference (final values)

Point estimate

0.4

Confidence interval

level

95%

sides

2-sided

lower limit

-0.9

upper limit

1.5

Notes
[4] - The null hypothesis associated with the SAE safety objective was that the upper limit of the two-sided 95% confidence interval for the difference between the MenACWY and routine vaccine groups in the proportion of subjects experiencing at least one SAE (PMenACWY + Routine Vaccines – PRoutine Vaccines) was ≥5%.

Secondary: 3. Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination

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End point title

3. Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination ^[5]

End point description

To compare the percentage of subjects who reported local and systemic solicited adverse events from day 1 to day 7 after each vaccination with MenACWY-CRM197 given concomitantly with routine vaccinations to the routine vaccinations alone group.

End point type

Secondary

End point timeframe

15 minutes to Day 7

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis is associated to this endpoint.

End point values	MenACWY-CRM197 + Routine Vaccines (Detailed)	Routine Vaccines (Detailed)
Number of subjects analysed	1313	451
Units: Percentages of subjects
Any Local (2 month vaccination) (N=1313, 451)	53	56
Injection Site Tenderness (N=1301, 446)	46	49
Injection Site Erythema (N=1297, 445)	17	21
Injection Site Induration (N=1297, 446)	8	16
Any Local (4 month vaccination) (N=1262, 420)	46	54
Injection Site Tenderness (N=1255, 418)	37	42
Injection Site Erythema (N=1257, 417)	19	29
Injection Site Induration (N=1257, 417)	9	17
Any Local (6 month vaccination) (N=1120, 374)	41	50
Injection Site Tenderness (N=1106, 372)	30	37
Injection Site Erythema (N=1104, 370)	22	29
Injection Site Induration (N=1107, 370)	9	19
Any Local (12 month vaccination) (N=1102, 355)	47	57
Injection Site Tenderness (N=1098, 353)	39	50
Injection Site Erythema (N=1095, 349)	21	30
Injection Site Induration (N=1095, 351)	10	23
Any Systemic (2 month vaccination) (N=1313, 451)	77	73
Rash (N=1296, 446)	3	3
Change in Eating Habits (N=1289, 446)	23	24
Sleepiness (N=1297, 447)	52	52
Persistent crying (N=1299,46)	42	40
Irritability (N=1300, 446)	59	59
Vomiting (N=1298, 446)	10	9
Diarrhea (N=1299, 446)	16	11
Fever ( ≥ 38°C) (N=1297, 446)	3	2
Analges.Antipyr.Meds (N=1302, 448)	66	60
Any Systemic (4 month vaccination) (N=1262, 420)	65	63
Rash (N=1253, 416)	3	4
Change in Eating Habits (N=1245, 414)	18	17
Sleepiness (N=1253, 416)	38	37
Persistent Crying (N=1254, 417)	31	28
Irritability (N=1254, 416)	50	48
Vomiting (N=1254, 416)	8	6
Diarrhea (N=1255, 416)	11	8
Fever ( ≥ 38°C) (N=1251, 416)	4	6
Analges.Antipyr.Meds (N=1254, 416)	58	55
Any Systemic (6 month vaccination) (N=1120, 374)	58	54
Rash (N=1101, 367)	3	3
Change in Eating Habits (N=1094, 367)	17	14
Sleepiness (N=1104, 367)	31	29
Persistent Crying (N=1103, 368)	26	20
Irritability (N=1104, 369)	46	41
Vomiting (N=1106, 369)	6	4
Diarrhea (N=1102, 369)	8	6
Fever ( ≥ 38°C) (N=1101, 368	7	6
Analges.Antipyr.Meds (N=1103, 370)	53	49
Any Systemic (12 month vaccination) (N=1102, 355)	63	62
Rash (N=1093, 353)	4	5
Change in Eating Habits (N=1089, 348)	18	16
Sleepiness (N=1096, 353)	30	29
Persistent Crying (N=1094, 353)	28	24
Irritability (N=1094, 354)	50	49
Vomiting (N=1094, 353)	5	4
Diarrhea (N=1094, 353)	12	9
Fever ( ≥ 38°C) (N=1092, 353)	9	8
Analges.Antipyr.Meds (N=1095, 354)	49	50

No statistical analyses for this end point

Secondary: 4. Number of Subjects Who Reported Unsolicited Adverse Events After Any Vaccination

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End point title

4. Number of Subjects Who Reported Unsolicited Adverse Events After Any Vaccination

End point description

Safety data with medically attended events were collected throughout the study in all safety groups and all unsolicited AEs were collected from Day 1 to Day 7 after each vaccination in the detailed safety groups. Possibly or Probably Related AEs were only assessed in the MenACWY-CRM197 + Routine Vaccines (All) arm.

End point type

Secondary

End point timeframe

Day 1 (2 months of age) to 18 months of age

End point values	Safety population (ACWY-All)	Safety population (RVAX-All)
Number of subjects analysed	5760	1968
Units: Subjects
Any AE	4848	1659
Any SAE-Total	354	114
Possibly or Probably Related AEs	520	2
AEs Leading to Premature Withdrawals	44	8
Deaths	7	1

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

2 months to 18 months of age

Adverse event reporting additional description

Post-injection solicited Adverse Events (AEs) and all unsolicited AEs were collected from Days 1-7 after each vaccination in the detailed groups. Medically attended AEs and Serious AEs were collected throughout the study period. Subjects who terminated early were followed for 6 months post final dose for safety.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

14.1

Reporting group title

MenACWY-CRM197 + Routine Vaccines (All)

Reporting group description

Infants received one vaccination of MenACWY-CRM197 vaccine at 2, 4, 6 and 12 months of age and one vaccination of routine vaccines (according to the local vaccination schedule) - DTaP: 2, 4, 6, 15 months, IPV: 2, 4, 6, months, Hib: 2, 4, 6, 15 months, Pneumococcal conjugate: 2, 4, 6, 12 months, MMR, Varicella, Hepatitis A: 12 months. HBV and rotavirus vaccines should be administered according to ACIP guidelines during the first year of life. Routine vaccines given to subjects in these arms will be consistent with the US ACIP recommended vaccines. All (Detailed and Non-Detailed subjects): Detailed - subjects who provided Reactogenicity and all AEs for 7 days, SAEs and medically attended AEs; Non-Detailed - subjects who only provided SAEs and medically attended AEs.

Reporting group title

Routine Vaccines (All)

Reporting group description

Infants received one vaccination of routine vaccines (according to the local vaccination schedule) - DTaP: 2, 4, 6, 15 months, IPV: 2, 4, 6, months, Hib: 2, 4, 6, 15 months, Pneumococcal conjugate: 2, 4, 6, 12 months, MMR, Varicella, and Hepatitis A: 12 months. HBV and rotavirus vaccines should be administered according to ACIP guidelines during the first year of life. Routine vaccines given to subjects in these arms will be consistent with the US ACIP recommended vaccines. All (Detailed and Non-Detailed subjects): Detailed - subjects who provided Reactogenicity and all AEs for 7 days, SAEs and medically attended AEs; Non-Detailed - subjects who only provided SAEs and medically attended AEs.

Serious adverse events	MenACWY-CRM197 + Routine Vaccines (All)	Routine Vaccines (All)
Total subjects affected by serious adverse events
subjects affected / exposed	354 / 5760 (6.15%)	114 / 1968 (5.79%)
number of deaths (all causes)	7	1
number of deaths resulting from adverse events	0	0
Vascular disorders
Angiopathy
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Kawasaki's disease
subjects affected / exposed	4 / 5760 (0.07%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	2 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vasculitis
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Surgical and medical procedures
Hernia repair
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Inguinal hernia repair
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Brain death
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Hernia
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	7 / 5760 (0.12%)	3 / 1968 (0.15%)
occurrences causally related to treatment / all	1 / 6	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
Balanoposthitis
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Scrotal mass
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Adenoidal hypertrophy
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Apnoea
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Asthma
subjects affected / exposed	6 / 5760 (0.10%)	2 / 1968 (0.10%)
occurrences causally related to treatment / all	0 / 6	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Atelectasis
subjects affected / exposed	2 / 5760 (0.03%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchial hyperreactivity
subjects affected / exposed	6 / 5760 (0.10%)	6 / 1968 (0.30%)
occurrences causally related to treatment / all	0 / 6	0 / 6
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchomalacia
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchospasm
subjects affected / exposed	2 / 5760 (0.03%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cough
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Epistaxis
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Hypoxia
subjects affected / exposed	3 / 5760 (0.05%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pulmonary oedema
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Respiratory distress
subjects affected / exposed	12 / 5760 (0.21%)	3 / 1968 (0.15%)
occurrences causally related to treatment / all	0 / 15	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Status asthmaticus
subjects affected / exposed	1 / 5760 (0.02%)	3 / 1968 (0.15%)
occurrences causally related to treatment / all	0 / 2	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Wheezing
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Breath holding
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Drug abuse
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Mental status changes
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Investigations
Electrocardiogram Qt prolonged
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Accidental poisoning
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Contusion
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Craniocerebral injury
subjects affected / exposed	5 / 5760 (0.09%)	2 / 1968 (0.10%)
occurrences causally related to treatment / all	0 / 5	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Electrical burn
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Fall
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Head injury
subjects affected / exposed	1 / 5760 (0.02%)	2 / 1968 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Foreign body
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Humerus fracture
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Injury
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skull fracture
subjects affected / exposed	1 / 5760 (0.02%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Post procedural complication
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
subdural haemorrhage
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Subdural haematoma
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Thermal burn
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tibia fracture
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Upper limb fracture
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital, familial and genetic disorders
Anomalous pulmonary venous connection
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital absence of bile ducts
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital aplastic anaemia
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Craniosynostosis
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cryptorchism
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hamartoma
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Mitochondrial enzyme deficiency
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Osteogenesis imperfecta
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Patent ductus arteriosus
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Phimosis
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pyloric stenosis
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vitello-intestinal duct remnant
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Congenital cardiovascular anomaly
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Cardiac disorders
Cardiac arrest
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Cyanosis
subjects affected / exposed	2 / 5760 (0.03%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Supraventricular tachycardia
subjects affected / exposed	1 / 5760 (0.02%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ventricular tachycardia
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (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
Acute disseminated encephalomyelitis
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Convulsion
subjects affected / exposed	5 / 5760 (0.09%)	3 / 1968 (0.15%)
occurrences causally related to treatment / all	0 / 6	0 / 4
deaths causally related to treatment / all	0 / 0	0 / 0
Epilepsy
subjects affected / exposed	2 / 5760 (0.03%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Febrile convulsion
subjects affected / exposed	9 / 5760 (0.16%)	6 / 1968 (0.30%)
occurrences causally related to treatment / all	1 / 10	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Myoclonic epilepsy
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hydrocephalus
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Presyncope
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Syncope
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Tremor
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	2 / 5760 (0.03%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Imune Thrombocytopenic Purpura
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Iron deficiency anaemia
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Febrile neutropenia
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Leukocytosis
subjects affected / exposed	2 / 5760 (0.03%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Thrombocytopenia
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lymphadenitis
subjects affected / exposed	4 / 5760 (0.07%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lymphadenopathy
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Eye disorders
Retinal haemorrhage
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (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
subjects affected / exposed	2 / 5760 (0.03%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Constipation
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	5 / 5760 (0.09%)	3 / 1968 (0.15%)
occurrences causally related to treatment / all	0 / 5	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Enteritis
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Enterocolitis
subjects affected / exposed	3 / 5760 (0.05%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastritis
subjects affected / exposed	2 / 5760 (0.03%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrooesophageal reflux disease
subjects affected / exposed	3 / 5760 (0.05%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ileus
subjects affected / exposed	1 / 5760 (0.02%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Inguinal hernia
subjects affected / exposed	2 / 5760 (0.03%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Incarcerated inguinal hernia
alternative dictionary used: MedDRA 17.1
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intussusception
subjects affected / exposed	4 / 5760 (0.07%)	3 / 1968 (0.15%)
occurrences causally related to treatment / all	0 / 5	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Stomatitis
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Vomiting
subjects affected / exposed	3 / 5760 (0.05%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hepatobiliary disorders
Jaundice
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Skin and subcutaneous tissue disorders
Dermal cyst
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Dermatitis atopic
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Erythema multiforme
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urticaria
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Renal failure acute
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Renal mass
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Vesicoureteric reflux
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (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
Acute tonsillitis
subjects affected / exposed	1 / 5760 (0.02%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Adenovirus infection
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Arthritis bacterial
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Ascariasis
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bacteraemia
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bacterial diarrhoea
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bacterial tracheitis
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchiolitis
subjects affected / exposed	64 / 5760 (1.11%)	15 / 1968 (0.76%)
occurrences causally related to treatment / all	0 / 67	0 / 17
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchopneumonia
subjects affected / exposed	19 / 5760 (0.33%)	5 / 1968 (0.25%)
occurrences causally related to treatment / all	0 / 19	0 / 6
deaths causally related to treatment / all	0 / 1	0 / 0
Bronchitis
subjects affected / exposed	1 / 5760 (0.02%)	3 / 1968 (0.15%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	5 / 5760 (0.09%)	4 / 1968 (0.20%)
occurrences causally related to treatment / all	1 / 6	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0
Cellulitis staphylococcal
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Cellulitis streptococcal
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Chest wall abscess
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Croup infectious
subjects affected / exposed	10 / 5760 (0.17%)	5 / 1968 (0.25%)
occurrences causally related to treatment / all	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea infectious
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Dysentery
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Enterovirus infection
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Escherichia urinary tract infection
subjects affected / exposed	1 / 5760 (0.02%)	2 / 1968 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Exanthema subitum
subjects affected / exposed	0 / 5760 (0.00%)	3 / 1968 (0.15%)
occurrences causally related to treatment / all	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Furuncle
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	20 / 5760 (0.35%)	7 / 1968 (0.36%)
occurrences causally related to treatment / all	0 / 20	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis rotavirus
subjects affected / exposed	2 / 5760 (0.03%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis salmonella
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	7 / 5760 (0.12%)	3 / 1968 (0.15%)
occurrences causally related to treatment / all	0 / 7	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Genital abscess
subjects affected / exposed	2 / 5760 (0.03%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Groin abscess
subjects affected / exposed	2 / 5760 (0.03%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Haemophilus bacteraemia
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hand-foot-and-mouth disease
subjects affected / exposed	10 / 5760 (0.17%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 10	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Herpangina
subjects affected / exposed	4 / 5760 (0.07%)	2 / 1968 (0.10%)
occurrences causally related to treatment / all	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Incision site cellulitis
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infected cyst
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Influenza
subjects affected / exposed	3 / 5760 (0.05%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Klebsiella bacteraemia
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lobar pneumonia
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lymph node abscess
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Meningitis
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Meningitis enteroviral
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metapneumovirus infection
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Otitis media
subjects affected / exposed	2 / 5760 (0.03%)	3 / 1968 (0.15%)
occurrences causally related to treatment / all	0 / 2	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Otitis media acute
subjects affected / exposed	1 / 5760 (0.02%)	3 / 1968 (0.15%)
occurrences causally related to treatment / all	0 / 1	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0
Periorbital cellulitis
subjects affected / exposed	3 / 5760 (0.05%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Peritonsillar abscess
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pharyngitis
subjects affected / exposed	2 / 5760 (0.03%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	31 / 5760 (0.54%)	10 / 1968 (0.51%)
occurrences causally related to treatment / all	0 / 35	0 / 10
deaths causally related to treatment / all	0 / 2	0 / 0
Pharyngotonsillitis
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumococcal bacteraemia
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia adenoviral
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia influenzal
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia respiratory syncytial viral
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia viral
subjects affected / exposed	3 / 5760 (0.05%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 1	0 / 0
Pyelonephritis
subjects affected / exposed	1 / 5760 (0.02%)	2 / 1968 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pyelonephritis acute
subjects affected / exposed	4 / 5760 (0.07%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory syncytial virus bronchiolitis
subjects affected / exposed	20 / 5760 (0.35%)	7 / 1968 (0.36%)
occurrences causally related to treatment / all	0 / 20	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory syncytial virus infection
subjects affected / exposed	4 / 5760 (0.07%)	2 / 1968 (0.10%)
occurrences causally related to treatment / all	0 / 4	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Rotavirus infection
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Sepsis
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Septic shock
subjects affected / exposed	3 / 5760 (0.05%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 2	0 / 0
Sinusitis
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Staphylococcal abscess
subjects affected / exposed	1 / 5760 (0.02%)	2 / 1968 (0.10%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Tonsillitis
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	4 / 5760 (0.07%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 4	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Urachal abscess
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (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	28 / 5760 (0.49%)	10 / 1968 (0.51%)
occurrences causally related to treatment / all	0 / 28	0 / 10
deaths causally related to treatment / all	0 / 1	0 / 0
Urinary tract infection enterococcal
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (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	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Varicella
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Viral diarrhoea
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Viral infection
subjects affected / exposed	4 / 5760 (0.07%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 4	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Wound infection
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
meningitis viral
subjects affected / exposed	2 / 5760 (0.03%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Staphylococcal infection
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Encephalitis
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Acute focal bacterial nephritis
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Atypical pneumonia
subjects affected / exposed	0 / 5760 (0.00%)	1 / 1968 (0.05%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
H1N1 influenza
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (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
Dehydration
subjects affected / exposed	18 / 5760 (0.31%)	9 / 1968 (0.46%)
occurrences causally related to treatment / all	0 / 19	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0
Failure to thrive
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Feeding disorder
subjects affected / exposed	1 / 5760 (0.02%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hypoglycaemia
subjects affected / exposed	2 / 5760 (0.03%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Metabolic acidosis
subjects affected / exposed	2 / 5760 (0.03%)	0 / 1968 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0

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

Non-serious adverse events	MenACWY-CRM197 + Routine Vaccines (All)	Routine Vaccines (All)
Total subjects affected by non serious adverse events
subjects affected / exposed	4662 / 5760 (80.94%)	1587 / 1968 (80.64%)
Nervous system disorders
Somnolence
alternative assessment type: Systematic
subjects affected / exposed	929 / 5760 (16.13%)	307 / 1968 (15.60%)
occurrences all number	2025	659
General disorders and administration site conditions
Injection site erythema
alternative assessment type: Systematic
subjects affected / exposed	519 / 5760 (9.01%)	241 / 1968 (12.25%)
occurrences all number	948	444
Injection site induration
alternative assessment type: Systematic
subjects affected / exposed	284 / 5760 (4.93%)	181 / 1968 (9.20%)
occurrences all number	448	311
Injection site pain
alternative assessment type: Systematic
subjects affected / exposed	916 / 5760 (15.90%)	338 / 1968 (17.17%)
occurrences all number	1890	720
Pyrexia
alternative assessment type: Systematic
subjects affected / exposed	1239 / 5760 (21.51%)	373 / 1968 (18.95%)
occurrences all number	1734	520
Crying
alternative assessment type: Systematic
subjects affected / exposed	859 / 5760 (14.91%)	277 / 1968 (14.08%)
occurrences all number	1767	517
Eye disorders
Conjunctivitis
subjects affected / exposed	732 / 5760 (12.71%)	234 / 1968 (11.89%)
occurrences all number	889	301
Gastrointestinal disorders
Teething
subjects affected / exposed	294 / 5760 (5.10%)	106 / 1968 (5.39%)
occurrences all number	336	122
Diarrhoea
alternative assessment type: Systematic
subjects affected / exposed	1181 / 5760 (20.50%)	356 / 1968 (18.09%)
occurrences all number	1750	500
Vomiting
alternative assessment type: Systematic
subjects affected / exposed	500 / 5760 (8.68%)	155 / 1968 (7.88%)
occurrences all number	674	195
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	504 / 5760 (8.75%)	171 / 1968 (8.69%)
occurrences all number	630	203
Skin and subcutaneous tissue disorders
Dermatitis diaper
subjects affected / exposed	628 / 5760 (10.90%)	201 / 1968 (10.21%)
occurrences all number	738	244
Eczema
subjects affected / exposed	399 / 5760 (6.93%)	145 / 1968 (7.37%)
occurrences all number	440	158
Rash
alternative assessment type: Systematic
subjects affected / exposed	307 / 5760 (5.33%)	109 / 1968 (5.54%)
occurrences all number	373	127
Psychiatric disorders
Irritability
alternative assessment type: Systematic
subjects affected / exposed	1148 / 5760 (19.93%)	405 / 1968 (20.58%)
occurrences all number	3051	955
Eating disorder
alternative assessment type: Systematic
subjects affected / exposed	593 / 5760 (10.30%)	187 / 1968 (9.50%)
occurrences all number	1029	313
Infections and infestations
Bronchiolitis
subjects affected / exposed	826 / 5760 (14.34%)	299 / 1968 (15.19%)
occurrences all number	1094	390
Croup infectious
subjects affected / exposed	284 / 5760 (4.93%)	98 / 1968 (4.98%)
occurrences all number	339	116
Bronchitis
subjects affected / exposed	446 / 5760 (7.74%)	153 / 1968 (7.77%)
occurrences all number	666	218
Gastroenteritis
subjects affected / exposed	524 / 5760 (9.10%)	179 / 1968 (9.10%)
occurrences all number	640	209
Influenza
subjects affected / exposed	415 / 5760 (7.20%)	124 / 1968 (6.30%)
occurrences all number	568	167
Nasopharyngitis
subjects affected / exposed	751 / 5760 (13.04%)	239 / 1968 (12.14%)
occurrences all number	1358	409
Otitis media
subjects affected / exposed	1579 / 5760 (27.41%)	551 / 1968 (28.00%)
occurrences all number	3472	1107
Otitis media acute
subjects affected / exposed	412 / 5760 (7.15%)	154 / 1968 (7.83%)
occurrences all number	736	263
Pharyngitis
subjects affected / exposed	609 / 5760 (10.57%)	208 / 1968 (10.57%)
occurrences all number	796	258
Sinusitis
subjects affected / exposed	296 / 5760 (5.14%)	93 / 1968 (4.73%)
occurrences all number	370	111
Upper respiratory tract infection
subjects affected / exposed	2358 / 5760 (40.94%)	842 / 1968 (42.78%)
occurrences all number	5140	1751
Viral infection
subjects affected / exposed	591 / 5760 (10.26%)	175 / 1968 (8.89%)
occurrences all number	748	210

More information

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Were there any global substantial amendments to the protocol? Yes

16 Feb 2009

Amendment 1. Addition of detailed safety arm; addition of 1000 control subjects; primary objective changed from descriptive to comparison with statistical testing; standard core routine vaccines defined; DTaP and Hib at 15 months of age.

14 May 2009

Amendment 2. The major changes incorporated into this version of the protocol were related to AE collection as follows: - Instead of only collecting serious and medically significant AEs, the protocol was modified to include collection of medically attended AEs from postvaccination day 8 through end of study for groups 3 and 4 subjects and for the duration of the trial for group 1 and 2 subjects. All AEs were collected from Day 1 to Day 7 postvaccination for Groups 3 and 4 (unchanged). - The definitions of relatedness of AEs were modified so that an AE would now be considered related to the study vaccine unless there was clear evidence of an alternative cause. - Review of the trial data by an independent Data Monitoring Committee was added to trial procedures.

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

http://www.ncbi.nlm.nih.gov/pubmed/24397906

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Clinical trials

Clinical Trial Results:
A Phase 3b, Open-Label, Randomized, Parallel-Group, Multi-Center Study to Evaluate the Safety of Novartis MenACWY Conjugate Vaccine when Administered with Routine Infant Vaccinations to Healthy Infants

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: 1. Percentages of Subjects With At Least One Severe Systemic Reaction After Any Vaccination

Primary: 1. Percentages of Subjects With At Least One Severe Systemic Reaction After Any Vaccination

Secondary: 2. Percentages of Subjects With At Least One Serious Adverse Event During the Entire Study Period

Secondary: 2. Percentages of Subjects With At Least One Serious Adverse Event During the Entire Study Period

Secondary: 3. Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination

Secondary: 3. Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination

Secondary: 4. Number of Subjects Who Reported Unsolicited Adverse Events After Any Vaccination

Secondary: 4. Number of Subjects Who Reported Unsolicited Adverse Events After Any Vaccination

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A Phase 3b, Open-Label, Randomized, Parallel-Group, Multi-Center Study to Evaluate the Safety of Novartis MenACWY Conjugate Vaccine when Administered with Routine Infant Vaccinations to Healthy Infants

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: 1. Percentages of Subjects With At Least One Severe Systemic Reaction After Any Vaccination

Primary: 1. Percentages of Subjects With At Least One Severe Systemic Reaction After Any Vaccination

Secondary: 2. Percentages of Subjects With At Least One Serious Adverse Event During the Entire Study Period

Secondary: 2. Percentages of Subjects With At Least One Serious Adverse Event During the Entire Study Period

Secondary: 3. Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination

Secondary: 3. Percentages of Subjects Reporting Solicited Adverse Events, After Each Vaccination

Secondary: 4. Number of Subjects Who Reported Unsolicited Adverse Events After Any Vaccination

Secondary: 4. Number of Subjects Who Reported Unsolicited Adverse Events After Any Vaccination

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

Online references

More information

Clinical Trial Results:
A Phase 3b, Open-Label, Randomized, Parallel-Group, Multi-Center Study to Evaluate the Safety of Novartis MenACWY Conjugate Vaccine when Administered with Routine Infant Vaccinations to Healthy Infants