Trial Outcomes & Findings for Safety and Immunogenicity of One Dose of Seasonal Trivalent Influenza Virus Vaccine (TIVf, Purified Surface Antigen, Inactivated, Egg Derived) in Adults Aged 18 Years and Above (NCT NCT01640327)

Last Updated: 2015-11-24

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 antigen assay. As per the European (CHMP) criteria seroconversion or significant increase in titer was 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 was 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

2015-11-24

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 TIVf vaccination	≥61 Y Subjects ≥61 years of age who received one TIVf vaccination
Overall Study STARTED	63	63
Overall Study COMPLETED	63	63
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Immunogenicity of One Dose of Seasonal Trivalent Influenza Virus Vaccine (TIVf, Purified Surface Antigen, Inactivated, Egg Derived) 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 TIVf vaccination	≥61 Y n=63 Participants Subjects ≥61 years of age who received one TIVf vaccination	Total n=126 Participants Total of all reporting groups
Age, Continuous	33.5 Years STANDARD_DEVIATION 10.6 • n=5 Participants	68.3 Years STANDARD_DEVIATION 5.1 • n=7 Participants	50.9 Years STANDARD_DEVIATION 19.3 • n=5 Participants
Sex: Female, Male Female	38 Participants n=5 Participants	36 Participants n=7 Participants	74 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	27 Participants n=7 Participants	52 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 TIVf vaccination	≥61 Y n=63 Participants Subjects ≥61 years of age who received one TIVf vaccination
Percentage of Subjects With Seroconversion or Significant Increase in HI Titer Against Each of Three Vaccine Strains After One Vaccination of TIVf A/H1N1	83 Percentages of Subjects Interval 71.0 to 91.0	60 Percentages of Subjects Interval 47.0 to 72.0
Percentage of Subjects With Seroconversion or Significant Increase in HI Titer Against Each of Three Vaccine Strains After One Vaccination of TIVf A/H3N2	70 Percentages of Subjects Interval 57.0 to 81.0	48 Percentages of Subjects Interval 35.0 to 61.0
Percentage of Subjects With Seroconversion or Significant Increase in HI Titer Against Each of Three Vaccine Strains After One Vaccination of TIVf B	49 Percentages of Subjects Interval 36.0 to 62.0	10 Percentages of Subjects Interval 4.0 to 20.0

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 was \>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 TIVf vaccination	≥61 Y n=63 Participants Subjects ≥61 years of age who received one TIVf vaccination
Geometric Mean Ratio of Subjects Against Each of Three Vaccine Strains After One Vaccination of TIVf A/H1N1	23 Ratio Interval 15.0 to 34.0	6.15 Ratio Interval 4.36 to 8.66
Geometric Mean Ratio of Subjects Against Each of Three Vaccine Strains After One Vaccination of TIVf A/H3N2	6.78 Ratio Interval 5.02 to 9.16	3.81 Ratio Interval 2.9 to 4.99
Geometric Mean Ratio of Subjects Against Each of Three Vaccine Strains After One Vaccination of TIVf B	4.37 Ratio Interval 3.38 to 5.64	1.61 Ratio Interval 1.38 to 1.89

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 TIVf 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 TIVf vaccination	≥61 Y n=63 Participants Subjects ≥61 years of age who received one TIVf vaccination
Percentage of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVf A/H1N1 (Day 1)	60 Percentages of Subjects Interval 47.0 to 72.0	49 Percentages of Subjects Interval 36.0 to 62.0
Percentage of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVf A/H1N1 (Day 22)	98 Percentages of Subjects Interval 91.0 to 100.0	92 Percentages of Subjects Interval 82.0 to 97.0
Percentage of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVf A/H3N2 (Day 1)	79 Percentages of Subjects Interval 67.0 to 89.0	86 Percentages of Subjects Interval 75.0 to 93.0
Percentage of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVf A/H3N2 (Day 22)	98 Percentages of Subjects Interval 91.0 to 100.0	100 Percentages of Subjects Interval 94.0 to 100.0
Percentage of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVf B (Day 1)	8 Percentages of Subjects Interval 3.0 to 18.0	5 Percentages of Subjects Interval 1.0 to 13.0
Percentage of Subjects Who Achieved HI Titer ≥40 Against Each of Three Vaccine Strains After One Vaccination of TIVf B (Day 22)	65 Percentages of Subjects Interval 52.0 to 77.0	19 Percentages of Subjects Interval 10.0 to 31.0

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 the TIVf vaccination.

Outcome measures

Outcome measures
Measure	18-60 Y n=63 Participants Subjects ≥18 years to ≤60 years of age who received one TIVf vaccination	≥61 Y n=63 Participants Subjects ≥61 years of age who received one TIVf vaccination
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Sweating	11 Subjects	9 Subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Fatigue	15 Subjects	9 Subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Fever (≥38°C)	0 Subjects	0 Subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Injection site ecchymosis	1 Subjects	1 Subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Injection site erythema	5 Subjects	7 Subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Injection site induration	6 Subjects	2 Subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Injection site swelling	2 Subjects	4 Subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Injection site pain	35 Subjects	12 Subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Chills/shivering	2 Subjects	1 Subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Malaise	10 Subjects	4 Subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Myalgia	18 Subjects	10 Subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Arthralgia	0 Subjects	0 Subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Headache	14 Subjects	6 Subjects

Adverse Events

18-60 Y

Serious events: 0 serious events

Other events: 44 other events

Deaths: 0 deaths

≥61 Y

Serious events: 0 serious events

Other events: 29 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 TIVf vaccination	≥61 Y n=63 participants at risk Subjects ≥61 years of age who received one TIVf vaccination
General disorders Fatigue	23.8% 15/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.	14.3% 9/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.
General disorders Injection site erythema	7.9% 5/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.	9.5% 6/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.
General disorders Injection site induration	6.3% 4/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.	3.2% 2/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.
General disorders Injection site pain	55.6% 35/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.	19.0% 12/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.
General disorders Malaise	15.9% 10/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.	6.3% 4/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.
Musculoskeletal and connective tissue disorders Myalgia	28.6% 18/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.	15.9% 10/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.
Nervous system disorders Headache	22.2% 14/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.	9.5% 6/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.
Skin and subcutaneous tissue disorders Hyperhidrosis	17.5% 11/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.	14.3% 9/63 • 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