Trial Outcomes & Findings for Safety and Immunogenicity of a Cell Derived Subunit Trivalent Nonadjuvated Influenza Study Vaccine in Adults Aged 18 Years and Above (NCT NCT01640314)

Last Updated: 2016-02-17

Results Overview

Immunogenicity was measured as the percentage of subjects who achieved seroconversion or significant increase in hemagglutination inhibition (HI) titer, against each of three vaccine strains, three weeks after vaccination (day 22), evaluated using HI cell-derived antigen assay. As per the European (CHMP) criteria, seroconversion or significant increase in titer is defined as the percentage of subjects with a prevaccination HI titer \<10 to a postvaccination HI titer ≥40; or in subjects with a prevaccination HI titer ≥10, a ≥4-fold increase in postvaccination HI antibody titer. This criterion is met according to CHMP guideline if percentage of subjects achieving seroconversion or significant increase in HI titer is \>40% (≥18 years to ≤60 years) or 30% (≥61 years).

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

126 participants

Primary outcome timeframe

Day 22

Results posted on

2016-02-17

Participant Flow

Subjects were enrolled at one study centre in Germany.

All enrolled subjects were included in the trial.

Participant milestones

Participant milestones
Measure	18-60 Y Subjects ≥18 years to ≤60 years of age who received one TIVc vaccination	≥ 61 Y Subjects ≥61 years of age who received one TIVc vaccination
Overall Study STARTED	63	63
Overall Study COMPLETED	63	62
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	18-60 Y Subjects ≥18 years to ≤60 years of age who received one TIVc vaccination	≥ 61 Y Subjects ≥61 years of age who received one TIVc vaccination
Overall Study Protocol Violation	0	1

Baseline Characteristics

Safety and Immunogenicity of a Cell Derived Subunit Trivalent Nonadjuvated Influenza Study Vaccine in Adults Aged 18 Years and Above

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	18-60 Y n=63 Participants Subjects ≥18 years to ≤60 years of age who received one TIVc vaccination	≥ 61 Y n=63 Participants Subjects ≥61 years of age who received one TIVc vaccination	Total n=126 Participants Total of all reporting groups
Age, Continuous	37.4 years STANDARD_DEVIATION 11.4 • n=5 Participants	68.0 years STANDARD_DEVIATION 4.7 • n=7 Participants	52.7 years STANDARD_DEVIATION 17.7 • n=5 Participants
Sex: Female, Male Female	33 Participants n=5 Participants	31 Participants n=7 Participants	64 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants	32 Participants n=7 Participants	62 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 22

Population: Analysis was done on the per-protocol (PP) set, i.e. the subjects who received the vaccine correctly; provided evaluable serum samples at the relevant time points; and had no major protocol violations as defined prior to analysis.

Outcome measures

Outcome measures
Measure	18-60 Y n=63 Participants Subjects ≥18 years to ≤60 years of age who received one TIVc vaccination	≥ 61 Y n=62 Participants Subjects ≥61 years of age who received one TIVc vaccination
Percentages of Subjects With Seroconversion or Significant Increase in HI Titer Against Each of Three Vaccine Strains After One Vaccination of TIVc A/H1N1	73 Percentages Interval 60.0 to 83.0	58 Percentages Interval 45.0 to 70.0
Percentages of Subjects With Seroconversion or Significant Increase in HI Titer Against Each of Three Vaccine Strains After One Vaccination of TIVc A/H3N2	67 Percentages Interval 54.0 to 78.0	45 Percentages Interval 32.0 to 58.0
Percentages of Subjects With Seroconversion or Significant Increase in HI Titer Against Each of Three Vaccine Strains After One Vaccination of TIVc B	63 Percentages Interval 50.0 to 75.0	42 Percentages Interval 30.0 to 55.0

PRIMARY outcome

Timeframe: Day 22

Population: Analysis was done on the PP set.

Geometric mean ratio (GMR) of subjects was calculated as the ratio of postvaccination to prevaccination HI geometric mean titers (GMTs), directed against each of three vaccine strains, three weeks after vaccination (day 22). The CHMP criterion was met if the geometric mean increase (GMR, day 22/day 1) in HI antibody titer is \>2.5 (≥18 years to ≤60 years) or \>2.0 (≥61 years).

Outcome measures

Outcome measures
Measure	18-60 Y n=63 Participants Subjects ≥18 years to ≤60 years of age who received one TIVc vaccination	≥ 61 Y n=62 Participants Subjects ≥61 years of age who received one TIVc vaccination
Geometric Mean Ratio of Subjects Against Each of Three Vaccine Strains After One Vaccination of TIVc A/H1N1	13 Ratio Interval 8.75 to 20.0	5.79 Ratio Interval 4.12 to 8.12
Geometric Mean Ratio of Subjects Against Each of Three Vaccine Strains After One Vaccination of TIVc A/H3N2	6.38 Ratio Interval 4.5 to 9.06	4.21 Ratio Interval 2.96 to 5.97
Geometric Mean Ratio of Subjects Against Each of Three Vaccine Strains After One Vaccination of TIVc B	5.63 Ratio Interval 4.11 to 7.7	3.54 Ratio Interval 2.65 to 4.72

PRIMARY outcome

Timeframe: Day 1 and 22

Population: Analysis was done on the PP set.

Immunogenicity was measured as the percentage of subjects achieving HI titer ≥40 against each of three vaccine strains at baseline (day 1) and three weeks after TIVc vaccination (day 22). This criterion was met according to CHMP guideline if percentage of subjects achieving HI titer ≥40 is \>70% (≥18 years to ≤60) or 60% (≥61 years).

Outcome measures

Outcome measures
Measure	18-60 Y n=63 Participants Subjects ≥18 years to ≤60 years of age who received one TIVc vaccination	≥ 61 Y n=62 Participants Subjects ≥61 years of age who received one TIVc vaccination
Percentages of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVc A/H1N1 (Day 1)	56 Percentages Interval 42.0 to 68.0	61 Percentages Interval 48.0 to 73.0
Percentages of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVc B (Day 1)	54 Percentages Interval 41.0 to 67.0	40 Percentages Interval 28.0 to 54.0
Percentages of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVc A/H1N1 (Day 22)	98 Percentages Interval 91.0 to 100.0	100 Percentages Interval 94.0 to 100.0
Percentages of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVc A/H3N2 (Day 1)	86 Percentages Interval 75.0 to 93.0	85 Percentages Interval 74.0 to 93.0
Percentages of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVc A/H3N2 (Day 22)	100 Percentages Interval 94.0 to 100.0	100 Percentages Interval 94.0 to 100.0
Percentages of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVc B (Day 22)	98 Percentages Interval 91.0 to 100.0	85 Percentages Interval 74.0 to 93.0

SECONDARY outcome

Timeframe: From day 1 through day 4 postvaccination

Population: Analysis was done on the safety dataset i.e. the subjects in the exposed population who provided postvaccination safety data.

Safety was assessed as the number of subjects who reported solicited local and systemic reactions from day 1 up to and including day 4 after TIVc vaccination.

Outcome measures

Outcome measures
Measure	18-60 Y n=63 Participants Subjects ≥18 years to ≤60 years of age who received one TIVc vaccination	≥ 61 Y n=63 Participants Subjects ≥61 years of age who received one TIVc vaccination
Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Injection site ecchymosis	1 Number of subjects	4 Number of subjects
Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Injection site erythema	1 Number of subjects	0 Number of subjects
Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Injection site swelling	1 Number of subjects	2 Number of subjects
Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Injection site induration	0 Number of subjects	2 Number of subjects
Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Injection site pain	29 Number of subjects	17 Number of subjects
Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Chills/shivering	1 Number of subjects	1 Number of subjects
Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Malaise	5 Number of subjects	2 Number of subjects
Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Myalgia	27 Number of subjects	12 Number of subjects
Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Arthralgia	2 Number of subjects	0 Number of subjects
Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Headache	13 Number of subjects	4 Number of subjects
Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Sweating	10 Number of subjects	7 Number of subjects
Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Fatigue	15 Number of subjects	7 Number of subjects
Number of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Fever (≥38°C)	0 Number of subjects	0 Number of subjects

SECONDARY outcome

Timeframe: Day 1 to Day 22

Population: Analysis was done on the safety set population.

The number of subjects in both age groups reporting any unsolicited AEs between Day 1 to Day 22 after receiving one dose of TIVc.

Outcome measures

Outcome measures
Measure	18-60 Y n=63 Participants Subjects ≥18 years to ≤60 years of age who received one TIVc vaccination	≥ 61 Y n=63 Participants Subjects ≥61 years of age who received one TIVc vaccination
Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc. Serious AEs	0 Number of Subjects	0 Number of Subjects
Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc. AEs leading to withdrawal	0 Number of Subjects	0 Number of Subjects
Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc. Any AEs	9 Number of Subjects	12 Number of Subjects
Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc. At least possibly related AEs	5 Number of Subjects	7 Number of Subjects
Number of Subjects Reporting Unsolicited Adverse Events After Receiving One Dose of TIVc. At least possibly related SAEs	0 Number of Subjects	0 Number of Subjects

Adverse Events

18-60 Y

Serious events: 0 serious events

Other events: 45 other events

Deaths: 0 deaths

≥ 61 Y

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	18-60 Y n=63 participants at risk Subjects ≥18 years to ≤60 years of age who received one TIVc vaccination	≥ 61 Y n=63 participants at risk Subjects ≥61 years of age who received one TIVc vaccination
General disorders Fatigue	23.8% 15/63 • Number of events 15 • From day 1 through day 22 Serious adverse events (SAEs) were collected from day 1 through day 22.	11.1% 7/63 • Number of events 7 • From day 1 through day 22 Serious adverse events (SAEs) were collected from day 1 through day 22.
General disorders Injection site haemorrhage	1.6% 1/63 • Number of events 1 • From day 1 through day 22 Serious adverse events (SAEs) were collected from day 1 through day 22.	6.3% 4/63 • Number of events 4 • From day 1 through day 22 Serious adverse events (SAEs) were collected from day 1 through day 22.
General disorders Injection site pain	46.0% 29/63 • Number of events 29 • From day 1 through day 22 Serious adverse events (SAEs) were collected from day 1 through day 22.	27.0% 17/63 • Number of events 17 • From day 1 through day 22 Serious adverse events (SAEs) were collected from day 1 through day 22.
General disorders Malaise	7.9% 5/63 • Number of events 5 • From day 1 through day 22 Serious adverse events (SAEs) were collected from day 1 through day 22.	3.2% 2/63 • Number of events 2 • From day 1 through day 22 Serious adverse events (SAEs) were collected from day 1 through day 22.
Musculoskeletal and connective tissue disorders Myalgia	42.9% 27/63 • Number of events 27 • From day 1 through day 22 Serious adverse events (SAEs) were collected from day 1 through day 22.	19.0% 12/63 • Number of events 12 • From day 1 through day 22 Serious adverse events (SAEs) were collected from day 1 through day 22.
Nervous system disorders Headache	20.6% 13/63 • Number of events 13 • From day 1 through day 22 Serious adverse events (SAEs) were collected from day 1 through day 22.	6.3% 4/63 • Number of events 4 • From day 1 through day 22 Serious adverse events (SAEs) were collected from day 1 through day 22.
Skin and subcutaneous tissue disorders Hyperhidrosis	15.9% 10/63 • Number of events 10 • From day 1 through day 22 Serious adverse events (SAEs) were collected from day 1 through day 22.	11.1% 7/63 • Number of events 7 • From day 1 through day 22 Serious adverse events (SAEs) were collected from day 1 through day 22.

Additional Information

Posting Director

Novartis Vaccines and Diagnostics

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place