Trial Outcomes & Findings for Safety and Immunogenicity of a Subunit Trivalent Nonadjuvated Influenza Study Vaccine in Adults Aged 18 Years and Above (NCT NCT01636102)

Last Updated: 2015-11-30

Results Overview

Immunogenicity was measured as the percentage of subjects who achieved seroconversion or significant increase in single radial hemolysis (SRH) area, against each of three vaccine strains, three weeks after vaccination (day 22), evaluated using SRH assay. Seroconversion or significant increase in SRH area was defined as the percentage of subjects with a negative prevaccination serum (SRH area ≤4 mm2) to a postvaccination SRH area ≥25 mm2; or a significant increase in antibody titer from a non-negative prevaccination serum, i.e., at least a 50% increase in area. The European (CHMP) criterion is met if percentage of subjects achieving seroconversion or significant increase in SRH area is \>40% (≥18 years to ≤60 years) or 30% (≥61 years).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

126 participants

Primary outcome timeframe

Day 22

Results posted on

2015-11-30

Participant Flow

Subjects were enrolled at 1 site in Belgium.

All subjects enrolled were included in the trial.

Participant milestones

Participant milestones
Measure	18-60 Y Subjects ≥18 years to ≤60 years of age who received one TIV vaccination	≥61 Y Subjects ≥61 years of age who received one TIV 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 a 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 TIV vaccination	≥61 Y n=63 Participants Subjects ≥61 years of age who received one TIV vaccination	Total n=126 Participants Total of all reporting groups
Age, Continuous	37.9 years STANDARD_DEVIATION 12.8 • n=5 Participants	69.2 years STANDARD_DEVIATION 5.7 • n=7 Participants	53.6 years STANDARD_DEVIATION 18.5 • n=5 Participants
Sex: Female, Male Female	39 Participants n=5 Participants	26 Participants n=7 Participants	65 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	37 Participants n=7 Participants	61 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=62 Participants Subjects ≥18 years to ≤60 years of age who received one TIV vaccination	≥61 Y n=62 Participants Subjects ≥61 years of age who received one TIV vaccination
Percentage of Subjects Who Achieved Seroconversion or Significant Increase in SRH Area Against Each of Three Vaccine Strains After One Vaccination of TIV A/H1N1	84 Percentages of subjects Interval 72.0 to 92.0	53 Percentages of subjects Interval 40.0 to 66.0
Percentage of Subjects Who Achieved Seroconversion or Significant Increase in SRH Area Against Each of Three Vaccine Strains After One Vaccination of TIV A/H3N2	81 Percentages of subjects Interval 69.0 to 90.0	65 Percentages of subjects Interval 51.0 to 76.0
Percentage of Subjects Who Achieved Seroconversion or Significant Increase in SRH Area Against Each of Three Vaccine Strains After One Vaccination of TIV B	69 Percentages of subjects Interval 56.0 to 80.0	73 Percentages of subjects Interval 60.0 to 83.0

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 SRH geometric mean areas (GMAs), 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 SRH antibody area is \>2.5 (≥18 years to ≤60 years) or \>2.0 (≥61 years).

Outcome measures

Outcome measures
Measure	18 - 60 Y n=62 Participants Subjects ≥18 years to ≤60 years of age who received one TIV vaccination	≥61 Y n=62 Participants Subjects ≥61 years of age who received one TIV vaccination
Geometric Mean Ratio of Subjects Against Each of Three Vaccine Strains After One Vaccination of TIV A/H1N1	5.7 Ratio Interval 4.3 to 7.55	2.88 Ratio Interval 2.26 to 3.65
Geometric Mean Ratio of Subjects Against Each of Three Vaccine Strains After One Vaccination of TIV A/H3N2	5.52 Ratio Interval 4.16 to 7.31	3.02 Ratio Interval 2.35 to 3.86
Geometric Mean Ratio of Subjects Against Each of Three Vaccine Strains After One Vaccination of TIV B	3.72 Ratio Interval 2.69 to 5.15	4.06 Ratio Interval 3.12 to 5.28

PRIMARY outcome

Timeframe: Day 1 and 22

Population: Analysis was done on the PP set.

Immunogenicity was measured as the percentage of subjects achieving SRH area ≥25 mm2 against each of three vaccine strains at baseline (day 1) and three weeks after TIV vaccination (day 22). This criterion was met according to CHMP guideline if percentage of subjects achieving SRH area ≥25 mm2 is \>70% (≥18 years to ≤60) or 60% (≥61 years).

Outcome measures

Outcome measures
Measure	18 - 60 Y n=62 Participants Subjects ≥18 years to ≤60 years of age who received one TIV vaccination	≥61 Y n=62 Participants Subjects ≥61 years of age who received one TIV vaccination
Percentage of Subjects Who Achieved SRH Area ≥25 mm2 Against Each of Three Vaccine Strains After One Vaccination of TIV A/H1N1 (Day 1)	34 Percentages of subjects Interval 22.0 to 47.0	27 Percentages of subjects Interval 17.0 to 40.0
Percentage of Subjects Who Achieved SRH Area ≥25 mm2 Against Each of Three Vaccine Strains After One Vaccination of TIV A/H1N1 (Day 22)	95 Percentages of subjects Interval 87.0 to 99.0	71 Percentages of subjects Interval 58.0 to 82.0
Percentage of Subjects Who Achieved SRH Area ≥25 mm2 Against Each of Three Vaccine Strains After One Vaccination of TIV A/H3N2 (Day 1)	23 Percentages of subjects Interval 13.0 to 35.0	45 Percentages of subjects Interval 32.0 to 58.0
Percentage of Subjects Who Achieved SRH Area ≥25 mm2 Against Each of Three Vaccine Strains After One Vaccination of TIV A/H3N2 (Day 22)	85 Percentages of subjects Interval 74.0 to 93.0	92 Percentages of subjects Interval 82.0 to 97.0
Percentage of Subjects Who Achieved SRH Area ≥25 mm2 Against Each of Three Vaccine Strains After One Vaccination of TIV B (Day 1)	61 Percentages of subjects Interval 48.0 to 73.0	21 Percentages of subjects Interval 12.0 to 33.0
Percentage of Subjects Who Achieved SRH Area ≥25 mm2 Against Each of Three Vaccine Strains After One Vaccination of TIV B (Day 22)	97 Percentages of subjects Interval 89.0 to 100.0	82 Percentages of subjects Interval 70.0 to 91.0

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 TIV vaccination.

Outcome measures

Outcome measures
Measure	18 - 60 Y n=62 Participants Subjects ≥18 years to ≤60 years of age who received one TIV vaccination	≥61 Y n=63 Participants Subjects ≥61 years of age who received one TIV vaccination
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Injection site ecchymosis	0 Number of subjects	1 Number of subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Injection site erythema	3 Number of subjects	4 Number of subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Injection site induration	4 Number of subjects	0 Number of subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Injection site swelling	4 Number of subjects	1 Number of subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Chills/shivering	0 Number of subjects	0 Number of subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Malaise	2 Number of subjects	1 Number of subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Myalgia	5 Number of subjects	3 Number of subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Injection site pain	24 Number of subjects	9 Number of subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Arthralgia	2 Number of subjects	1 Number of subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Headache	9 Number of subjects	6 Number of subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Sweating	3 Number of subjects	2 Number of subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Fatigue	8 Number of subjects	3 Number of subjects
Numbers of Subjects Who Reported Solicited Local and Systemic Reactions (Day 1 - Day 4 Postvaccination) Body temperature (≥38°C)	0 Number of subjects	0 Number of subjects

Adverse Events

18-60 Y

Serious events: 0 serious events

Other events: 28 other events

Deaths: 0 deaths

≥61 Y

Serious events: 0 serious events

Other events: 18 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 TIV vaccination	≥61 Y n=63 participants at risk Subjects ≥61 years of age who received one TIV vaccination
General disorders Fatigue	12.7% 8/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.	4.8% 3/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.
General disorders Injection Site Erythema	4.8% 3/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.	7.9% 5/63 • 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.	0.00% 0/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.
General disorders Injection Site Pain	38.1% 24/63 • 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.
General disorders Injection Site Swelling	6.3% 4/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.	1.6% 1/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.
Musculoskeletal and connective tissue disorders Myalgia	7.9% 5/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.	4.8% 3/63 • From day 1 through day 22. Serious adverse events (SAEs) were collected from day 1 through day 22.
Nervous system disorders Headache	14.3% 9/63 • 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.

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

Restriction type: GT60