Trial Outcomes & Findings for Immunogenicity and Safety Study to Assess Influenza Vaccine Formulated With Haemagglutinin (HA) Antigen From Two Suppliers (NCT NCT01229371)

NCT ID: NCT01229371

Last Updated: 2013-09-09

Results Overview

The primary endpoints were the immunogenicity parameters for HA assessed via hemagglutinin inhibition method (HI). These parameters were analyzed according to the EMA "Note for guidance on harmonisation of requirements for influenza vaccines," 1997 and they were the following: 1. Seroprotection rate, defined as proportion of subjects with HI antibody titer ≥1:40, 2. Seroconversion rate, defined as proportion of subjects with ≥4-fold increase in HI antibody titer and with a titer of ≥1:40, 3. GMT of HI antibodies and fold-increase in GMT

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

440 participants

Primary outcome timeframe

3 weeks after vaccination (Day 22 ± 2 days)

Results posted on

2013-09-09

Participant Flow

Recruitment period: 19 October 2010 to 09 November 2010; outpatient study

Participant milestones

Participant milestones
Measure
Subjects ≥18 to ≤60 Years - AdImmune HA Antigen
Subjects ≥18 to ≤60 Years - CSL HA Antigen
Subjects >60 Years - AdImmune HA Antigen
Subjects >60 Years - CSL HA Antigen
Overall Study
STARTED
109
111
110
110
Overall Study
COMPLETED
109
110
110
110
Overall Study
NOT COMPLETED
0
1
0
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Subjects ≥18 to ≤60 Years - AdImmune HA Antigen
Subjects ≥18 to ≤60 Years - CSL HA Antigen
Subjects >60 Years - AdImmune HA Antigen
Subjects >60 Years - CSL HA Antigen
Overall Study
Withdrawal by Subject
0
1
0
0

Baseline Characteristics

Immunogenicity and Safety Study to Assess Influenza Vaccine Formulated With Haemagglutinin (HA) Antigen From Two Suppliers

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Subjects ≥18 to ≤60 Years - AdImmune HA Antigen
n=109 Participants
Subjects ≥18 to ≤60 Years - CSL HA Antigen
n=111 Participants
Subjects >60 Years - AdImmune HA Antigen
n=110 Participants
Subjects >60 Years - CSL HA Antigen
n=110 Participants
Total
n=440 Participants
Total of all reporting groups
Age, Categorical
<=18 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
0 Participants
n=4 Participants
0 Participants
n=21 Participants
Age, Categorical
Between 18 and 65 years
109 Participants
n=5 Participants
111 Participants
n=7 Participants
47 Participants
n=5 Participants
53 Participants
n=4 Participants
320 Participants
n=21 Participants
Age, Categorical
>=65 years
0 Participants
n=5 Participants
0 Participants
n=7 Participants
63 Participants
n=5 Participants
57 Participants
n=4 Participants
120 Participants
n=21 Participants
Age Continuous
39.5 years
STANDARD_DEVIATION 11.18 • n=5 Participants
39.9 years
STANDARD_DEVIATION 12.10 • n=7 Participants
66.5 years
STANDARD_DEVIATION 5.50 • n=5 Participants
66.4 years
STANDARD_DEVIATION 5.06 • n=4 Participants
53.1 years
STANDARD_DEVIATION 16.14 • n=21 Participants
Sex: Female, Male
Female
54 Participants
n=5 Participants
50 Participants
n=7 Participants
49 Participants
n=5 Participants
53 Participants
n=4 Participants
206 Participants
n=21 Participants
Sex: Female, Male
Male
55 Participants
n=5 Participants
61 Participants
n=7 Participants
61 Participants
n=5 Participants
57 Participants
n=4 Participants
234 Participants
n=21 Participants
Region of Enrollment
Switzerland
109 participants
n=5 Participants
111 participants
n=7 Participants
110 participants
n=5 Participants
110 participants
n=4 Participants
440 participants
n=21 Participants

PRIMARY outcome

Timeframe: 3 weeks after vaccination (Day 22 ± 2 days)

Population: Intent-to-treat population, vaccinated subjects with available pre- and post-vaccination titers

The primary endpoints were the immunogenicity parameters for HA assessed via hemagglutinin inhibition method (HI). These parameters were analyzed according to the EMA "Note for guidance on harmonisation of requirements for influenza vaccines," 1997 and they were the following: 1. Seroprotection rate, defined as proportion of subjects with HI antibody titer ≥1:40, 2. Seroconversion rate, defined as proportion of subjects with ≥4-fold increase in HI antibody titer and with a titer of ≥1:40, 3. GMT of HI antibodies and fold-increase in GMT

Outcome measures

Outcome measures
Measure
Subjects ≥18 to ≤60 Years - AdImmune HA Antigen
n=109 Participants
Subjects ≥18 to ≤60 Years - CSL HA Antigen
n=110 Participants
Subjects >60 Years - AdImmune HA Antigen
n=110 Participants
Subjects >60 Years - CSL HA Antigen
n=110 Participants
Immunogenicity - Geometric Mean Titer Fold Increase From Baseline
GMT fold increase from baseline: A/H1N1
3.5 GMT fold increase
Interval 2.8 to 4.3
4.0 GMT fold increase
Interval 3.3 to 5.0
4.5 GMT fold increase
Interval 3.6 to 5.7
3.4 GMT fold increase
Interval 2.8 to 4.2
Immunogenicity - Geometric Mean Titer Fold Increase From Baseline
GMT fold increase from baseline: A/H3N2
2.5 GMT fold increase
Interval 2.1 to 3.0
2.5 GMT fold increase
Interval 2.1 to 2.9
2.2 GMT fold increase
Interval 1.8 to 2.6
1.9 GMT fold increase
Interval 1.5 to 2.3
Immunogenicity - Geometric Mean Titer Fold Increase From Baseline
GMT fold increase from baseline: B-strain
3.2 GMT fold increase
Interval 2.6 to 3.8
3.1 GMT fold increase
Interval 2.6 to 3.7
1.9 GMT fold increase
Interval 1.7 to 2.2
2.1 GMT fold increase
Interval 1.8 to 2.4

PRIMARY outcome

Timeframe: 3 weeks after vaccination (Day 22 ± 2 days)

Population: Intent-to-treat population, vaccinated subjects with available pre- and post-vaccination titers

The primary endpoints were the immunogenicity parameters for HA assessed via hemagglutinin inhibition method (HI). These parameters were analyzed according to the EMA "Note for guidance on harmonisation of requirements for influenza vaccines," 1997 and they were the following: 1. Seroprotection rate, defined as proportion of subjects with HI antibody titer ≥1:40, 2. Seroconversion rate, defined as proportion of subjects with ≥4-fold increase in HI antibody titer and with a titer of ≥1:40, 3. GMT of HI antibodies and fold-increase in GMT

Outcome measures

Outcome measures
Measure
Subjects ≥18 to ≤60 Years - AdImmune HA Antigen
n=109 Participants
Subjects ≥18 to ≤60 Years - CSL HA Antigen
n=110 Participants
Subjects >60 Years - AdImmune HA Antigen
n=110 Participants
Subjects >60 Years - CSL HA Antigen
n=110 Participants
Immunogenicity - Seroprotection Rate
Percentage of subjects seroprotected: A/H1N1
99.1 percentage subjects
Interval 95.0 to 100.0
98.2 percentage subjects
Interval 93.6 to 99.8
92.7 percentage subjects
Interval 82.8 to 96.8
90.0 percentage subjects
Interval 82.8 to 94.9
Immunogenicity - Seroprotection Rate
Percentage of subjects seroprotected: A/H3N2
99.1 percentage subjects
Interval 95.0 to 100.0
99.1 percentage subjects
Interval 95.0 to 100.0
100 percentage subjects
Interval 96.7 to 100.0
99.1 percentage subjects
Interval 95.0 to 100.0
Immunogenicity - Seroprotection Rate
Percentage of subjects seroprotected: B-strain
96.3 percentage subjects
Interval 90.9 to 99.0
97.3 percentage subjects
Interval 92.2 to 99.4
85.5 percentage subjects
Interval 77.5 to 91.5
86.4 percentage subjects
Interval 78.5 to 92.2

PRIMARY outcome

Timeframe: 3 weeks after vaccination (Day 22 ± 2 days)

Population: Intent-to-treat population, vaccinated subjects with available pre- and post-vaccination titers

The primary endpoints were the immunogenicity parameters for HA assessed via hemagglutinin inhibition method (HI). These parameters were analyzed according to the EMA "Note for guidance on harmonisation of requirements for influenza vaccines," 1997 and they were the following: 1. Seroprotection rate, defined as proportion of subjects with HI antibody titer ≥1:40, 2. Seroconversion rate, defined as proportion of subjects with ≥4-fold increase in HI antibody titer and with a titer of ≥1:40, 3. GMT of HI antibodies and fold-increase in GMT

Outcome measures

Outcome measures
Measure
Subjects ≥18 to ≤60 Years - AdImmune HA Antigen
n=109 Participants
Subjects ≥18 to ≤60 Years - CSL HA Antigen
n=110 Participants
Subjects >60 Years - AdImmune HA Antigen
n=110 Participants
Subjects >60 Years - CSL HA Antigen
n=110 Participants
Immunogenicity - Seroconversion Rate
Percentage of subjects seroprotected: A/H1N1
45.0 percentage subjects
Interval 35.4 to 54.8
52.7 percentage subjects
Interval 43.0 to 62.3
54.5 percentage subjects
Interval 44.8 to 64.1
43.6 percentage subjects
Interval 34.2 to 53.4
Immunogenicity - Seroconversion Rate
Percentage of subjects seroprotected: A/H3N2
27.5 percentage subjects
Interval 19.4 to 36.9
29.1 percentage subjects
Interval 20.8 to 38.5
25.5 percentage subjects
Interval 17.6 to 34.6
17.3 percentage subjects
Interval 10.7 to 25.7
Immunogenicity - Seroconversion Rate
Percentage of subjects seroprotected: B-strain
40.4 percentage subjects
Interval 31.1 to 50.2
44.5 percentage subjects
Interval 35.1 to 54.3
20.9 percentage subjects
Interval 13.7 to 29.7
20.0 percentage subjects
Interval 13.0 to 28.7

SECONDARY outcome

Timeframe: Baseline (Day 1) and 3 weeks after vaccination (Day 22 ± 2 days)

Population: Safety population, all vaccinated subjects

Solicited local and systemic AEs, Unsolicited AEs, Tolerability and acceptability Unsolicited AEs were collected from baseline (Day 1) to 3 weeks after vaccination (Day 22 ± 2 days). Solicited local and systemic AEs were collected by subjects diary from Day 1 (day of vaccination) to Day 4

Outcome measures

Outcome measures
Measure
Subjects ≥18 to ≤60 Years - AdImmune HA Antigen
n=109 Participants
Subjects ≥18 to ≤60 Years - CSL HA Antigen
n=111 Participants
Subjects >60 Years - AdImmune HA Antigen
n=110 Participants
Subjects >60 Years - CSL HA Antigen
n=110 Participants
Number of Participants With Local and Systemic Adverse Events
Unsolicited AEs
14 participants
21 participants
8 participants
11 participants
Number of Participants With Local and Systemic Adverse Events
AEs (unsolicited and solicited)
57 participants
58 participants
25 participants
30 participants
Number of Participants With Local and Systemic Adverse Events
Solicited local AEs
45 participants
41 participants
18 participants
21 participants
Number of Participants With Local and Systemic Adverse Events
Solicited systemic AEs
14 participants
9 participants
6 participants
4 participants

Adverse Events

Subjects ≥18 to ≤60 Years - AdImmune HA Antigen

Serious events: 0 serious events
Other events: 57 other events
Deaths: 0 deaths

Subjects ≥18 to ≤60 Years - CSL HA Antigen

Serious events: 0 serious events
Other events: 58 other events
Deaths: 0 deaths

Subjects >60 Years - AdImmune HA Antigen

Serious events: 0 serious events
Other events: 25 other events
Deaths: 0 deaths

Subjects >60 Years - CSL HA Antigen

Serious events: 0 serious events
Other events: 30 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Subjects ≥18 to ≤60 Years - AdImmune HA Antigen
n=109 participants at risk
Subjects ≥18 to ≤60 Years - CSL HA Antigen
n=111 participants at risk
Subjects >60 Years - AdImmune HA Antigen
n=110 participants at risk
Subjects >60 Years - CSL HA Antigen
n=110 participants at risk
General disorders
Chills
6.4%
7/109 • Number of events 7
2.7%
3/111 • Number of events 3
3.6%
4/110 • Number of events 4
0.91%
1/110 • Number of events 1
General disorders
Fatigue
2.8%
3/109 • Number of events 3
1.8%
2/111 • Number of events 2
0.00%
0/110
0.91%
1/110 • Number of events 1
General disorders
Haemorrhage (at the injection site)
0.92%
1/109 • Number of events 1
3.6%
4/111 • Number of events 4
0.00%
0/110
0.91%
1/110 • Number of events 1
General disorders
Erythema (at the injection site)
6.4%
7/109 • Number of events 7
5.4%
6/111 • Number of events 6
8.2%
9/110 • Number of events 9
4.5%
5/110 • Number of events 5
General disorders
Induration (at the injection site)
10.1%
11/109 • Number of events 11
7.2%
8/111 • Number of events 8
8.2%
9/110 • Number of events 9
4.5%
5/110 • Number of events 5
General disorders
Pain (at the injection site)
34.9%
38/109 • Number of events 38
35.1%
39/111 • Number of events 39
12.7%
14/110 • Number of events 14
12.7%
14/110 • Number of events 14
General disorders
Malaise
11.0%
12/109 • Number of events 13
3.6%
4/111 • Number of events 4
5.5%
6/110 • Number of events 6
2.7%
3/110 • Number of events 3
Infections and infestations
Nasopharyngitis
0.92%
1/109 • Number of events 1
1.8%
2/111 • Number of events 2
0.91%
1/110 • Number of events 1
1.8%
2/110 • Number of events 3
Respiratory, thoracic and mediastinal disorders
Cough
0.92%
1/109 • Number of events 1
2.7%
3/111 • Number of events 3
1.8%
2/110 • Number of events 2
0.00%
0/110

Additional Information

Medical Affairs Director

Crucell Switzerland AG

Phone: +41(0)319806111

Results disclosure agreements

  • Principal investigator is a sponsor employee The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period between 30 to 90 days (depending on the complexitiy of the work) from the time submitted to the sponsor for review.
  • Publication restrictions are in place

Restriction type: OTHER