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Clinical Trial Results:
A Phase II, Multicenter, Randomized, Observer-blind, Placebo-controlled Study to Evaluate the Immunogenicity, Safety and Tolerability of CSL’s 2009 H1N1 Influenza Vaccine (CSL425) in a Healthy Pediatric Population.

Summary
EudraCT number	2015-000176-10
Trial protocol	Outside EU/EEA
Global end of trial date	04 Nov 2009

Results information
Results version number	v1(current)
This version publication date	30 Jun 2016
First version publication date	30 Jul 2015
Other versions

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

CSLCT-CAL-09-62

ISRCTN number

US NCT number

NCT00958243

WHO universal trial number (UTN)

Sponsor organisation name

CSL Limited

Sponsor organisation address

43 Poplar Rd, Parkville, Australia, 3052

Public contact

Clinical Program Director, bioCSL, bioCSL PTY LTD, biocsl.clinicaltrials@biocsl.com.au

Scientific contact

Clinical Program Director, bioCSL, bioCSL PTY LTD, biocsl.clinicaltrials@biocsl.com.au

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

16 Nov 2009

Is this the analysis of the primary completion data?

Yes

Primary completion date

04 Nov 2009

Global end of trial reached?

Yes

Global end of trial date

04 Nov 2009

Was the trial ended prematurely?

Main objective of the trial

To evaluate the immunogenicity of the 7.5 μg haemagglutinin (HA) and 15 μg HA antigen doses of 2009 H1N1 vaccine (H1N1 vaccine) in two cohorts of healthy children: Cohort A: participants aged 6 months to less than 3 years ; Cohort B: participants aged 3 years to less than 9 years.

Protection of trial subjects

This study was conducted under a United States (US) Investigational New Drug Application and in accordance with US guidelines and regulations, and in accordance with the World Medical Association Declaration of Helsinki.

Background therapy

Evidence for comparator

Actual start date of recruitment

24 Aug 2009

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 473

Worldwide total number of subjects

473

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)

129

Children (2-11 years)

344

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 Initiation Date: 24 August 2009 (First Participant First Visit) Active Study Completion Date: 04 November 2009 (Last Participant, Last Visit) This phase II pediatric study was conducted in 12 sites in the USA.

Screening details

Eligible participants were stratified by age to one of two cohorts (Cohort A: participants aged 6 months to <3 years; Cohort B: participants aged 3 to <9 years). After stratification, participants were randomised, in a 1:4:4 allocation ratio, to either placebo or one of the two HA antigen doses of H1N1 vaccine (7.5 ug or 15 ug).

Period 1 title

Overall Trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

Cohort A (6 months to < 3 years ) - placebo

Arm description

Arm type

Placebo

Investigational medicinal product name

thimerosal-free vaccine diluent

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

The placebo comprised thimerosal-free vaccine diluent. The placebo was supplied in pre-filled syringes. Participants in the placebo group received two vaccinations of 0.5mL of placebo, administered 21 days apart. The placebo was administered by intramuscular injection.

Cohort A (6 months to < 3 years) - 7.5 mcg dose

Arm description

Arm type

Experimental

Investigational medicinal product name

H1N1 vaccine - 7.5 mcg dose

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

The H1N1 vaccine, a monovalent, inactivated, split-virus vaccine, contains the HA antigen for the influenza strain A/California/7/2009(H1N1)v like virus (2009 H1N1) as recommended by the World Health Organization. The vaccine was supplied as a thimerosal-free suspension in pre-filled syringes. The dose of H1N1 vaccine was 7.5 mcg HA antigen per 0.25 mL dose. Participants received two vaccinations of their assigned dose, administered 21 days apart. Each dose was administered by intramuscular injection.

Cohort A (6 months to < 3 years) - 15 mcg dose

Arm description

Arm type

Experimental

Investigational medicinal product name

H1N1 vaccine - 15 mcg dose

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled pen

Routes of administration

Intramuscular use

Dosage and administration details

The H1N1 vaccine, a monovalent, inactivated, split-virus vaccine, contains the HA antigen for the influenza strain A/California/7/2009(H1N1)v like virus (2009 H1N1) as recommended by the World Health Organization. The vaccine was supplied as a thimerosal-free suspension in pre-filled syringes. The dose of H1N1 vaccine was 15 mcg HA antigen per 0.5mL dose. Participants received two vaccinations of their assigned dose, administered 21 days apart. Each dose was administered by intramuscular injection.

Cohort B (3 years to <9 years) - placebo

Arm description

Arm type

Placebo

Investigational medicinal product name

thimerosal-free vaccine diluent

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Cohort B (3 years to < 9 years) - 7.5 mcg dose

Arm description

Arm type

Experimental

Investigational medicinal product name

H1N1 vaccine - 7.5 mcg dose

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

Cohort B (3 years to < 9 years) - 15 mcg dose

Arm description

Arm type

Experimental

Investigational medicinal product name

H1N1 vaccine - 15 mcg dose

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled pen

Routes of administration

Intramuscular use

Dosage and administration details

The H1N1 vaccine, a monovalent, inactivated, split-virus vaccine, contains the HA antigen for the influenza strain A/California/7/2009(H1N1)v like virus (2009 H1N1) as recommended by the World Health Organization. The vaccine was supplied as a thimerosal-free suspension in pre-filled syringes. The dose of H1N1 vaccine was 15 mcg HA antigen per 0.5mL dose. Participants received two vaccinations of their assigned dose, administered 21 days apart. Each dose was administered by intramuscular injection.

Number of subjects in period 1	Cohort A (6 months to < 3 years ) - placebo	Cohort A (6 months to < 3 years) - 7.5 mcg dose	Cohort A (6 months to < 3 years) - 15 mcg dose	Cohort B (3 years to <9 years) - placebo	Cohort B (3 years to < 9 years) - 7.5 mcg dose	Cohort B (3 years to < 9 years) - 15 mcg dose
Started	26	105	96	28	109	109
Completed	24	99	82	25	100	99
Not completed	2	6	14	3	9	10
Consent withdrawn by subject	-	1	3	1	1	5
Lost to follow-up	2	5	11	2	8	5

Baseline characteristics

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Reporting group title

Cohort A (6 months to < 3 years ) - placebo

Reporting group description

Reporting group title

Cohort A (6 months to < 3 years) - 7.5 mcg dose

Reporting group description

Reporting group title

Cohort A (6 months to < 3 years) - 15 mcg dose

Reporting group description

Reporting group title

Cohort B (3 years to <9 years) - placebo

Reporting group description

Reporting group title

Cohort B (3 years to < 9 years) - 7.5 mcg dose

Reporting group description

Reporting group title

Cohort B (3 years to < 9 years) - 15 mcg dose

Reporting group description

Reporting group values	Cohort A (6 months to < 3 years ) - placebo	Cohort A (6 months to < 3 years) - 7.5 mcg dose	Cohort A (6 months to < 3 years) - 15 mcg dose	Cohort B (3 years to <9 years) - placebo	Cohort B (3 years to < 9 years) - 7.5 mcg dose	Cohort B (3 years to < 9 years) - 15 mcg dose	Total
Number of subjects	26	105	96	28	109	109	473
Age categorical
Units: Subjects
<= 18 years	26	105	96	28	109	109	473
between 18 and 65 years	0	0	0	0	0	0	0
>= 65 years	0	0	0	0	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	1.87 ± 0.77	1.73 ± 0.72	1.85 ± 0.66	5.9 ± 1.71	5.94 ± 1.71	5.91 ± 1.7	-
Gender categorical
Units: Subjects
Female	11	57	44	13	53	50	228
Male	15	48	52	15	56	59	245

End points

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Reporting group title

Cohort A (6 months to < 3 years ) - placebo

Reporting group description

Reporting group title

Cohort A (6 months to < 3 years) - 7.5 mcg dose

Reporting group description

Reporting group title

Cohort A (6 months to < 3 years) - 15 mcg dose

Reporting group description

Reporting group title

Cohort B (3 years to <9 years) - placebo

Reporting group description

Reporting group title

Cohort B (3 years to < 9 years) - 7.5 mcg dose

Reporting group description

Reporting group title

Cohort B (3 years to < 9 years) - 15 mcg dose

Reporting group description

Primary: Seroconversion Rate 21 Days After First Study Vaccination.

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End point title

Seroconversion Rate 21 Days After First Study Vaccination. ^[1]

End point description

Seroconversion rate: the percentage of participants achieving seroconversion in HI antibody titer. Seroconversion is defined as participants with a pre-vaccination titer of less than 1:10 achieving a post-vaccination HI antibody titer of 1:40 or more; or participants with a pre-vaccination HI titer of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titer. The Evaluable Population (for the first vaccination) comprised all randomized participants who received the first study vaccine; provided both pre- and post-vaccination blood samples; were not excluded from analyses (e.g., the use of a prohibited medication or a laboratory confirmed infection with 2009 H1N1 between Visit 1 and Visit 3).

End point type

Primary

End point timeframe

21 days after the first study vaccination.

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: Data were analysed using descriptive statistics only.

End point values	Cohort A (6 months to < 3 years ) - placebo	Cohort A (6 months to < 3 years) - 7.5 mcg dose	Cohort A (6 months to < 3 years) - 15 mcg dose	Cohort B (3 years to <9 years) - placebo	Cohort B (3 years to < 9 years) - 7.5 mcg dose	Cohort B (3 years to < 9 years) - 15 mcg dose
Number of subjects analysed	25	102	89	27	104	102
Units: percentage of participants
arithmetic mean (confidence interval 95%)	4 (0.1 to 20.4)	88.2 (80.4 to 93.8)	83.1 (73.7 to 90.2)	3.7 (0.1 to 19)	84.6 (76.2 to 90.9)	88.2 (80.4 to 93.8)

No statistical analyses for this end point

Primary: Seroconversion Rate 21 Days After Second Study Vaccination.

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End point title

Seroconversion Rate 21 Days After Second Study Vaccination. ^[2]

End point description

Seroconversion rate: the percentage of participants achieving seroconversion in HI antibody titer. Seroconversion is defined as participants with a pre-vaccination titer of less than 1:10 achieving a post-vaccination HI antibody titer of 1:40 or more; or participants with a pre-vaccination HI titer of 1:10 or more achieving a four-fold or greater increase in post-vaccination HI titer. The Evaluable Population (for the second vaccination) comprised all randomized participants who received the second study vaccine; provided both pre- and post-vaccination blood samples; were not excluded from analyses (e.g., the use of a prohibited medication or a laboratory confirmed infection with 2009 H1N1 between Visit 1 and Visit 3).

End point type

Primary

End point timeframe

Seroconversion Rate 21 Days After Second Study Vaccination.

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Data were analysed using descriptive statistics only.

End point values	Cohort A (6 months to < 3 years ) - placebo	Cohort A (6 months to < 3 years) - 7.5 mcg dose	Cohort A (6 months to < 3 years) - 15 mcg dose	Cohort B (3 years to <9 years) - placebo	Cohort B (3 years to < 9 years) - 7.5 mcg dose	Cohort B (3 years to < 9 years) - 15 mcg dose
Number of subjects analysed	21	90	80	26	98	98
Units: percentage of participants
arithmetic mean (confidence interval 95%)	28.6 (11.3 to 52.2)	98.9 (94 to 100)	100 (95.5 to 100)	15.4 (4.4 to 34.9)	98 (92.8 to 99.8)	99 (94.4 to 100)

No statistical analyses for this end point

Primary: Percentage of Participants Achieving an Hemagglutination Inhibition (HI) Antibody Titer of 1:40 or More 21 Days After First Study Vaccination.

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End point title

Percentage of Participants Achieving an Hemagglutination Inhibition (HI) Antibody Titer of 1:40 or More 21 Days After First Study Vaccination. ^[3]

End point description

The Evaluable Population (for the first vaccination) comprised all randomized participants who received the first study vaccine; provided both pre- and post-vaccination blood samples; were not excluded from analyses (e.g., the use of a prohibited medication or a laboratory confirmed infection with 2009 H1N1 between Visit 1 and Visit 3).

End point type

Primary

End point timeframe

21 days after the first study vaccination.

Notes
[3] - 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: Data were analysed using descriptive statistics only.

End point values	Cohort A (6 months to < 3 years ) - placebo	Cohort A (6 months to < 3 years) - 7.5 mcg dose	Cohort A (6 months to < 3 years) - 15 mcg dose	Cohort B (3 years to <9 years) - placebo	Cohort B (3 years to < 9 years) - 7.5 mcg dose	Cohort B (3 years to < 9 years) - 15 mcg dose
Number of subjects analysed	25	102	89	27	104	102
Units: percentage of participants
arithmetic mean (confidence interval 95%)	8 (1 to 26)	90.2 (82.7 to 95.2)	84.3 (75 to 91.1)	25.9 (11.1 to 46.3)	84.6 (76.2 to 90.9)	89.2 (81.5 to 94.5)

No statistical analyses for this end point

Primary: Percentage of Participants Achieving an Hemagglutination Inhibition (HI) Antibody Titer of 1:40 or More 21 Days After Second Study Vaccination.

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End point title

Percentage of Participants Achieving an Hemagglutination Inhibition (HI) Antibody Titer of 1:40 or More 21 Days After Second Study Vaccination. ^[4]

End point description

The Evaluable Population (for the second vaccination) comprised all randomized participants who received the second study vaccine; provided both pre- and post-vaccination blood samples; were not excluded from analyses (e.g., the use of a prohibited medication or a laboratory confirmed infection with 2009 H1N1 between Visit 1 and Visit 3).

End point type

Primary

End point timeframe

21 days after the second study vaccination.

Notes
[4] - 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: Data were analysed using descriptive statistics only.

End point values	Cohort A (6 months to < 3 years ) - placebo	Cohort A (6 months to < 3 years) - 7.5 mcg dose	Cohort A (6 months to < 3 years) - 15 mcg dose	Cohort B (3 years to <9 years) - placebo	Cohort B (3 years to < 9 years) - 7.5 mcg dose	Cohort B (3 years to < 9 years) - 15 mcg dose
Number of subjects analysed	21	90	80	26	98	98
Units: percentage of participants
arithmetic mean (confidence interval 95%)	28.6 (11.3 to 52.2)	98.9 (94 to 100)	100 (95.5 to 100)	34.6 (17.2 to 55.7)	98 (92.8 to 99.8)	100 (96.3 to 100)

No statistical analyses for this end point

Secondary: Frequency and Intensity of Solicited Adverse Events (AEs) After the First or Second Study Vaccination, Cohort A

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End point title

Frequency and Intensity of Solicited Adverse Events (AEs) After the First or Second Study Vaccination, Cohort A ^[5]

End point description

Grade 3 solicited AE definitions: Prevented normal daily activities or required medical intervention for systemic AEs; Cried when limb was moved/spontaneously painful (aged < 3 years) for injection site pain; Size > 30 mm for injection site redness and injection site induration/swelling; Oral temperature > 104.0°F (40.0°C) or axillary temperature > 103.1°F (39.5°C) for fevers. Safety Population comprised all randomized participants who received at least one dose of study vaccine and had provided follow-up safety data.

End point type

Secondary

End point timeframe

During the 7 days after each study vaccination.

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: Data were analysed using descriptive statistics only.

End point values	Cohort A (6 months to < 3 years ) - placebo	Cohort A (6 months to < 3 years) - 7.5 mcg dose	Cohort A (6 months to < 3 years) - 15 mcg dose
Number of subjects analysed	26	105	96
Units: percentage of participants
number (not applicable)
Any local solicited adverse event	42	44	37
Any pain	35	33	27
Grade 3 pain	0	0	0
Any redness	23	27	19
Grade 3 redness	0	0	0
Any swelling / induration	8	16	6
Grade 3 swelling / induration	0	0	0
Any systemic solicited adverse event	58	70	65
Any fever	23	25	43
Grade 3 fever	0	3	4
Any nausea / vomiting	8	11	15
Grade 3 nausea / vomiting	0	0	0
Any diarrhea	39	37	38
Grade 3 diarrhea	0	1	2
Any loss of appetite	12	24	22
Grade 3 loss of appetite	0	0	1
Any irritability	23	48	34
Grade 3 irritability	0	1	2

No statistical analyses for this end point

Secondary: Duration of Solicited Adverse Events After the First and Second Study Vaccination, Cohort A

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End point title

Duration of Solicited Adverse Events After the First and Second Study Vaccination, Cohort A ^[6]

End point description

Safety Population comprised all randomized participants who received at least one dose of study vaccine and had provided follow-up safety data. In Cohort A, Safety Population after the first vaccination are placebo group was n=26, 7.5 mcg group n=105 and 15 mcg group n=96; and n=25, n=101 and n=91 respectively after the second vaccination.

End point type

Secondary

End point timeframe

During the 7 days after each study vaccination.

Notes
[6] - 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: Data were analysed using descriptive statistics only.

End point values	Cohort A (6 months to < 3 years ) - placebo	Cohort A (6 months to < 3 years) - 7.5 mcg dose	Cohort A (6 months to < 3 years) - 15 mcg dose
Number of subjects analysed	26	105	96
Units: days
arithmetic mean (standard deviation)
Any pain after first vaccination	1 ± 0	1.52 ± 0.677	1.91 ± 1.743
Any redness after first vaccination	1.5 ± 0.577	2.2 ± 1.323	2.56 ± 1.459
Any swelling / induration after first vaccination	1.5 ± 0.707	1.63 ± 0.957	2 ± 1.549
Any fever after first vaccination	3.33 ± 3.215	1.32 ± 0.557	1.29 ± 0.893
Any nausea / vomiting after first vaccination	1 ± 0	1.43 ± 0.535	1.11 ± 0.333
Any diarrhea after first vaccination	1.67 ± 0.707	2.38 ± 1.996	3.95 ± 4.248
Any loss of appetite after first vaccination	2 ± 0	3.13 ± 2.5	2.07 ± 1.486
Any irritability after first vaccination	6 ± 7.81	2.08 ± 1.412	1.97 ± 1.224
Any pain after second vaccination	1.43 ± 0.787	1.57 ± 0.676	1.23 ± 0.599
Any redness after second vaccination	2.4 ± 2.608	2 ± 1.24	1.63 ± 0.916
Any swelling / induration after second vaccination	3 ± 0	3 ± 2.098	2.5 ± 0.707
Any fever after second vaccination	1.4 ± 0.894	1.4 ± 0.894	2.19 ± 2.344
Any nausea / vomiting after second vaccination	0 ± 0	1.27 ± 0.647	1.5 ± 0.837
Any diarrhea after second vaccination	8 ± 9.899	1.92 ± 1.248	4.33 ± 6.754
Any loss of appetite after second vaccination	1.5 ± 0.707	1.75 ± 1.183	3.6 ± 5.168
Any irritability after second vaccination	1.5 ± 0.577	1.81 ± 1.001	2.86 ± 4.597

No statistical analyses for this end point

Secondary: Frequency and Intensity of Solicited Adverse Events After the First or Second Study Vaccination, Cohort B

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End point title

Frequency and Intensity of Solicited Adverse Events After the First or Second Study Vaccination, Cohort B ^[7]

End point description

Grade 3 solicited AE definitions: Prevented normal daily activities or required medical intervention for systemic AEs; Prevented normal daily activities (aged >= 3 years) for injection site pain; Size > 30 mm for injection site redness and injection site induration/swelling; Oral temperature > 104.0°F (40.0°C) or axillary temperature > 103.1°F (39.5°C) for fevers. Safety Population comprised all randomized participants who received at least one dose of study vaccine and had provided follow-up safety data.

End point type

Secondary

End point timeframe

During the 7 days after each study vaccination.

Notes
[7] - 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: Data were analysed using descriptive statistics only.

End point values	Cohort B (3 years to <9 years) - placebo	Cohort B (3 years to < 9 years) - 7.5 mcg dose	Cohort B (3 years to < 9 years) - 15 mcg dose
Number of subjects analysed	28	107	109
Units: percentage of participants
number (not applicable)
Any local solicited adverse event	43	38	49
Any pain	29	34	40
Grade 3 pain	0	0	0
Any redness	29	18	26
Grade 3 redness	0	0	0
Any swelling / induration	11	13	17
Grade 3 swelling / induration	0	0	0
Any systemic solicited adverse event	46	44	46
Any fever	14	19	20
Grade 3 fever	0	0	0
Any nausea / vomiting	14	8	13
Grade 3 nausea / vomiting	0	2	1
Any diarrhea	21	8	9
Grade 3 diarrhea	0	1	0
Any headache	21	17	25
Grade 3 headache	0	1	0
Any malaise	21	27	20
Grade 3 malaise	4	0	0
Any myalgia	21	14	22
Grade 3 myalgia	0	0	0

No statistical analyses for this end point

Secondary: Duration of Solicited Adverse Events After the First and Second Study Vaccination, Cohort B

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End point title

Duration of Solicited Adverse Events After the First and Second Study Vaccination, Cohort B ^[8]

End point description

Safety Population comprised all randomized participants who received at least one dose of study vaccine and had provided follow-up safety data. In Cohort B, Safety Population after the first vaccination are placebo group n=28, 7.5 mcg group n=107 and 15 mcg group n=109; and n=27, n=105 and n=103 respectively after the second vaccination.

End point type

Secondary

End point timeframe

During the 7 days after each study vaccination.

Notes
[8] - 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: Data were analysed using descriptive statistics only.

End point values	Cohort B (3 years to <9 years) - placebo	Cohort B (3 years to < 9 years) - 7.5 mcg dose	Cohort B (3 years to < 9 years) - 15 mcg dose
Number of subjects analysed	28	107	109
Units: days
arithmetic mean (standard deviation)
Any pain after first vaccination	1.33 ± 0.516	1.63 ± 1.066	1.46 ± 0.691
Any redness after first vaccination	2.29 ± 1.254	2.17 ± 1.339	2.24 ± 1.809
Any swelling / induration after first vaccination	2 ± 1.732	1.8 ± 0.632	1.79 ± 0.975
Any fever after first vaccination	1.2 ± 0.447	1.12 ± 0.332	1.56 ± 0.856
Any nausea / vomiting after first vaccination	1 ± 0	1.25 ± 0.5	1 ± 0
Any diarrhea after first vaccination	1.13 ± 0.354	1 ± 0	1.22 ± 0.441
Any malaise after first vaccination	1.38 ± 0.744	0.47 ± 0.964	1.6 ± 0.995
Any myalgia after first vaccination	1.6 ± 0.548	1.42 ± 0.669	1.56 ± 0.984
Any headache after first vaccination	1.4 ± 0.894	1.15 ± 0.376	1.25 ± 0.645
Any pain after second vaccination	1.25 ± 0.5	1.56 ± 0.856	1.33 ± 0.555
Any redness after second vaccination	2 ± 0	1.67 ± 0.516	1.6 ± 0.699
Any swelling / induration after second vaccination	2 ± 0	1.17 ± 0.408	1.63 ± 0.744
Any fever after second vaccination	1 ± 0	1.4 ± 0.548	1.57 ± 1.134
Any nausea / vomiting after second vaccination	1 ± 0	1.25 ± 0.5	1.17 ± 0.408
Any diarrhea after second vaccination	1 ± 0	1 ± 0	1 ± 0
Any malaise after second vaccination	1.5 ± 0.707	1.75 ± 0.754	1.83 ± 1.467
Any myalgia after second vaccination	1 ± 0	1.38 ± 0.518	1.42 ± 0.669
Any headache after second vaccination	1.5 ± 0.707	1.38 ± 0.518	1.29 ± 0.488

No statistical analyses for this end point

Secondary: Frequency and Intensity of Unsolicited Adverse Events (UAE) After the First or Second Vaccination

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End point title

Frequency and Intensity of Unsolicited Adverse Events (UAE) After the First or Second Vaccination

End point description

UAE grading: Grade 1: Symptoms were easily tolerated and did not interfere with daily activities. Grade 2: Enough discomfort to cause some interference with daily activities. Grade 3: Symptoms that prevented normal, everyday activities. Safety Population comprised all randomized participants who received at least one dose of study vaccine and had provided follow-up safety data.

End point type

Secondary

End point timeframe

During the 21 days after each vaccination.

End point values	Cohort A (6 months to < 3 years ) - placebo	Cohort A (6 months to < 3 years) - 7.5 mcg dose	Cohort A (6 months to < 3 years) - 15 mcg dose	Cohort B (3 years to <9 years) - placebo	Cohort B (3 years to < 9 years) - 7.5 mcg dose	Cohort B (3 years to < 9 years) - 15 mcg dose
Number of subjects analysed	26	105	96	28	107	109
Units: percentage of participants
number (not applicable)
Proportion of participants with at least one UAE	69	52	55	50	49	41
Proportion of participants reported Grade 1 UAE	31	26	22	14	23	19
Proportion of participants reported Grade 2 UAE	39	22	27	25	21	17
Proportion of participants reported Grade 3 UAE	0	5	6	11	5	6

No statistical analyses for this end point

Secondary: Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs) and New Onset of Chronic Illness (NOCIs)

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End point title

Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs) and New Onset of Chronic Illness (NOCIs)

End point description

A NOCI was defined as the diagnosis of a new medical condition that was chronic in nature, including those potentially controllable by medication (e.g., diabetes, asthma). Safety Population comprised all randomized participants who received at least one dose of study vaccine and had provided follow-up safety data.

End point type

Secondary

End point timeframe

Up to 180 days after the last vaccination.

End point values	Cohort A (6 months to < 3 years ) - placebo	Cohort A (6 months to < 3 years) - 7.5 mcg dose	Cohort A (6 months to < 3 years) - 15 mcg dose	Cohort B (3 years to <9 years) - placebo	Cohort B (3 years to < 9 years) - 7.5 mcg dose	Cohort B (3 years to < 9 years) - 15 mcg dose
Number of subjects analysed	26	105	96	28	107	109
Units: percentage of participants
number (not applicable)
Proportion of participants with at least one SAE	0	2	3	0	0	0
Proportion of participants with related SAE	0	0	0	0	0	0
Proportion of participants with at least one AESI	0	0	0	0	0	0
Proportion of participants with related AESI	0	0	0	0	0	0
Proportion of participants with at least one NOCI	0	0	1	0	1	0
Proportion of participants with related NOCI	0	0	0	0	0	0

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

180 days after the last study vaccination for SAEs. 21 days after each study vaccination for unsolicited adverse events.

Adverse event reporting additional description

Other adverse events presented are unsolicited adverse events 21 days after either study vaccination by systematic assessment. SAEs were collected by non-systematic assessment.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

13.0

Reporting group title

Cohort A (6 months to < 3 years ) - placebo

Reporting group description

Reporting group title

Cohort A (6 months to < 3 years) - 7.5 mcg dose

Reporting group description

Reporting group title

Cohort A (6 months to < 3 years) - 15 mcg dose

Reporting group description

Reporting group title

Cohort B (3 years to <9 years) - placebo

Reporting group description

Reporting group title

Cohort B (3 years to < 9 years) - 7.5 mcg dose

Reporting group description

Reporting group title

Cohort B (3 years to < 9 years) - 15 mcg dose

Reporting group description

Serious adverse events	Cohort A (6 months to < 3 years ) - placebo	Cohort A (6 months to < 3 years) - 7.5 mcg dose	Cohort A (6 months to < 3 years) - 15 mcg dose	Cohort B (3 years to <9 years) - placebo	Cohort B (3 years to < 9 years) - 7.5 mcg dose	Cohort B (3 years to < 9 years) - 15 mcg dose
Total subjects affected by serious adverse events
subjects affected / exposed	0 / 26 (0.00%)	2 / 105 (1.90%)	3 / 96 (3.13%)	0 / 28 (0.00%)	0 / 107 (0.00%)	0 / 109 (0.00%)
number of deaths (all causes)	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0
Nervous system disorders
Ataxia
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 26 (0.00%)	1 / 105 (0.95%)	0 / 96 (0.00%)	0 / 28 (0.00%)	0 / 107 (0.00%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Mental status changes
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 26 (0.00%)	0 / 105 (0.00%)	1 / 96 (1.04%)	0 / 28 (0.00%)	0 / 107 (0.00%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bronchiolitis
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 26 (0.00%)	0 / 105 (0.00%)	1 / 96 (1.04%)	0 / 28 (0.00%)	0 / 107 (0.00%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 26 (0.00%)	0 / 105 (0.00%)	1 / 96 (1.04%)	0 / 28 (0.00%)	0 / 107 (0.00%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia viral
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 26 (0.00%)	0 / 105 (0.00%)	1 / 96 (1.04%)	0 / 28 (0.00%)	0 / 107 (0.00%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory syncytial virus infection
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 26 (0.00%)	0 / 105 (0.00%)	1 / 96 (1.04%)	0 / 28 (0.00%)	0 / 107 (0.00%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
alternative assessment type: Non-systematic
subjects affected / exposed	0 / 26 (0.00%)	1 / 105 (0.95%)	0 / 96 (0.00%)	0 / 28 (0.00%)	0 / 107 (0.00%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Cohort A (6 months to < 3 years ) - placebo	Cohort A (6 months to < 3 years) - 7.5 mcg dose	Cohort A (6 months to < 3 years) - 15 mcg dose	Cohort B (3 years to <9 years) - placebo	Cohort B (3 years to < 9 years) - 7.5 mcg dose	Cohort B (3 years to < 9 years) - 15 mcg dose
Total subjects affected by non serious adverse events
subjects affected / exposed	25 / 26 (96.15%)	58 / 105 (55.24%)	82 / 96 (85.42%)	22 / 28 (78.57%)	70 / 107 (65.42%)	49 / 109 (44.95%)
Nervous system disorders
Headache
subjects affected / exposed	0 / 26 (0.00%)	0 / 105 (0.00%)	1 / 96 (1.04%)	4 / 28 (14.29%)	8 / 107 (7.48%)	4 / 109 (3.67%)
occurrences all number	0	0	1	5	8	4
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	5 / 26 (19.23%)	8 / 105 (7.62%)	14 / 96 (14.58%)	6 / 28 (21.43%)	15 / 107 (14.02%)	10 / 109 (9.17%)
occurrences all number	6	8	15	9	17	11
Irritability
subjects affected / exposed	0 / 26 (0.00%)	2 / 105 (1.90%)	7 / 96 (7.29%)	0 / 28 (0.00%)	0 / 107 (0.00%)	3 / 109 (2.75%)
occurrences all number	0	2	7	0	0	5
Malaise
subjects affected / exposed	1 / 26 (3.85%)	2 / 105 (1.90%)	1 / 96 (1.04%)	2 / 28 (7.14%)	3 / 107 (2.80%)	1 / 109 (0.92%)
occurrences all number	1	3	1	2	3	1
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	1 / 26 (3.85%)	5 / 105 (4.76%)	5 / 96 (5.21%)	0 / 28 (0.00%)	7 / 107 (6.54%)	2 / 109 (1.83%)
occurrences all number	1	5	7	0	7	2
Teething
subjects affected / exposed	1 / 26 (3.85%)	5 / 105 (4.76%)	7 / 96 (7.29%)	0 / 28 (0.00%)	0 / 107 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	7	10	0	0	0
Vomiting
subjects affected / exposed	0 / 26 (0.00%)	4 / 105 (3.81%)	4 / 96 (4.17%)	2 / 28 (7.14%)	7 / 107 (6.54%)	2 / 109 (1.83%)
occurrences all number	0	4	5	2	7	2
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
subjects affected / exposed	10 / 26 (38.46%)	17 / 105 (16.19%)	14 / 96 (14.58%)	3 / 28 (10.71%)	6 / 107 (5.61%)	7 / 109 (6.42%)
occurrences all number	13	19	17	3	8	7
Cough
subjects affected / exposed	4 / 26 (15.38%)	9 / 105 (8.57%)	17 / 96 (17.71%)	3 / 28 (10.71%)	21 / 107 (19.63%)	15 / 109 (13.76%)
occurrences all number	6	11	21	3	22	17
Nasal congestion
subjects affected / exposed	1 / 26 (3.85%)	4 / 105 (3.81%)	11 / 96 (11.46%)	1 / 28 (3.57%)	3 / 107 (2.80%)	5 / 109 (4.59%)
occurrences all number	1	5	12	1	3	5
Infections and infestations
Ear infection
subjects affected / exposed	2 / 26 (7.69%)	2 / 105 (1.90%)	1 / 96 (1.04%)	1 / 28 (3.57%)	0 / 107 (0.00%)	0 / 109 (0.00%)
occurrences all number	2	2	1	1	0	0

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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

Clinical Trial Results:
A Phase II, Multicenter, Randomized, Observer-blind, Placebo-controlled Study to Evaluate the Immunogenicity, Safety and Tolerability of CSL’s 2009 H1N1 Influenza Vaccine (CSL425) in a Healthy Pediatric Population.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Seroconversion Rate 21 Days After First Study Vaccination.

Primary: Seroconversion Rate 21 Days After First Study Vaccination.

Primary: Seroconversion Rate 21 Days After Second Study Vaccination.

Primary: Seroconversion Rate 21 Days After Second Study Vaccination.

Primary: Percentage of Participants Achieving an Hemagglutination Inhibition (HI) Antibody Titer of 1:40 or More 21 Days After First Study Vaccination.

Primary: Percentage of Participants Achieving an Hemagglutination Inhibition (HI) Antibody Titer of 1:40 or More 21 Days After First Study Vaccination.

Primary: Percentage of Participants Achieving an Hemagglutination Inhibition (HI) Antibody Titer of 1:40 or More 21 Days After Second Study Vaccination.

Primary: Percentage of Participants Achieving an Hemagglutination Inhibition (HI) Antibody Titer of 1:40 or More 21 Days After Second Study Vaccination.

Secondary: Frequency and Intensity of Solicited Adverse Events (AEs) After the First or Second Study Vaccination, Cohort A

Secondary: Frequency and Intensity of Solicited Adverse Events (AEs) After the First or Second Study Vaccination, Cohort A

Secondary: Duration of Solicited Adverse Events After the First and Second Study Vaccination, Cohort A

Secondary: Duration of Solicited Adverse Events After the First and Second Study Vaccination, Cohort A

Secondary: Frequency and Intensity of Solicited Adverse Events After the First or Second Study Vaccination, Cohort B

Secondary: Frequency and Intensity of Solicited Adverse Events After the First or Second Study Vaccination, Cohort B

Secondary: Duration of Solicited Adverse Events After the First and Second Study Vaccination, Cohort B

Secondary: Duration of Solicited Adverse Events After the First and Second Study Vaccination, Cohort B

Secondary: Frequency and Intensity of Unsolicited Adverse Events (UAE) After the First or Second Vaccination

Secondary: Frequency and Intensity of Unsolicited Adverse Events (UAE) After the First or Second Vaccination

Secondary: Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs) and New Onset of Chronic Illness (NOCIs)

Secondary: Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs) and New Onset of Chronic Illness (NOCIs)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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 II, Multicenter, Randomized, Observer-blind, Placebo-controlled Study to Evaluate the Immunogenicity, Safety and Tolerability of CSL’s 2009 H1N1 Influenza Vaccine (CSL425) in a Healthy Pediatric Population.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Seroconversion Rate 21 Days After First Study Vaccination.

Primary: Seroconversion Rate 21 Days After First Study Vaccination.

Primary: Seroconversion Rate 21 Days After Second Study Vaccination.

Primary: Seroconversion Rate 21 Days After Second Study Vaccination.

Primary: Percentage of Participants Achieving an Hemagglutination Inhibition (HI) Antibody Titer of 1:40 or More 21 Days After First Study Vaccination.

Primary: Percentage of Participants Achieving an Hemagglutination Inhibition (HI) Antibody Titer of 1:40 or More 21 Days After First Study Vaccination.

Primary: Percentage of Participants Achieving an Hemagglutination Inhibition (HI) Antibody Titer of 1:40 or More 21 Days After Second Study Vaccination.

Primary: Percentage of Participants Achieving an Hemagglutination Inhibition (HI) Antibody Titer of 1:40 or More 21 Days After Second Study Vaccination.

Secondary: Frequency and Intensity of Solicited Adverse Events (AEs) After the First or Second Study Vaccination, Cohort A

Secondary: Frequency and Intensity of Solicited Adverse Events (AEs) After the First or Second Study Vaccination, Cohort A

Secondary: Duration of Solicited Adverse Events After the First and Second Study Vaccination, Cohort A

Secondary: Duration of Solicited Adverse Events After the First and Second Study Vaccination, Cohort A

Secondary: Frequency and Intensity of Solicited Adverse Events After the First or Second Study Vaccination, Cohort B

Secondary: Frequency and Intensity of Solicited Adverse Events After the First or Second Study Vaccination, Cohort B

Secondary: Duration of Solicited Adverse Events After the First and Second Study Vaccination, Cohort B

Secondary: Duration of Solicited Adverse Events After the First and Second Study Vaccination, Cohort B

Secondary: Frequency and Intensity of Unsolicited Adverse Events (UAE) After the First or Second Vaccination

Secondary: Frequency and Intensity of Unsolicited Adverse Events (UAE) After the First or Second Vaccination

Secondary: Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs) and New Onset of Chronic Illness (NOCIs)

Secondary: Incidence of Serious Adverse Events (SAEs), Adverse Events of Special Interest (AESIs) and New Onset of Chronic Illness (NOCIs)

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase II, Multicenter, Randomized, Observer-blind, Placebo-controlled Study to Evaluate the Immunogenicity, Safety and Tolerability of CSL’s 2009 H1N1 Influenza Vaccine (CSL425) in a Healthy Pediatric Population.