Trial Outcomes & Findings for Study to Evaluate Safety and Immunogenicity of Sub-unit Adjuvanted Influenza Vaccine Administered to Elderly Subjects, Formulation 2010-2011 (NCT NCT01152814)

Last Updated: 2016-01-27

Results Overview

Immunogenicity was measured as the percentage of participants who achieved seroconversion or significant increase in single radial hemolysis (SRH) area, against each of the three vaccine strains, three weeks after vaccination (day 22), evaluated using SRH assay. Seroconversion: proportion of participants with negative pre-vaccination serum and a post-vaccination serum area ≥ 25 mm2. Significant increase: proportion of participants with at least a 50% increase in area from positive pre-vaccination serum. Seroconversion or significant increase: proportion of participants with either seroconversion or significant increase. The European (Committee for Medicinal Products for Human Use \[CHMP\]) criterion is met, if percentage of participants achieving seroconversion or significant increase in SRH area is 30% (≥65 years).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

64 participants

Primary outcome timeframe

day 22

Results posted on

2016-01-27

Participant Flow

Overall, 64 participants ≥65 years of age were enrolled at 5 sites in Italy.

Blood samples for the determination of antibody titers were obtained prior to vaccination.

Participant milestones

Participant milestones
Measure	FLUAD Participants received a single intramuscular (IM) dose of 0.5 milliliter (mL) of FLUAD containing 15μg each of the three influenza antigens into the deltoid region of the non-dominant arm during the vaccination visit, according to the study protocol until Day 22.
Overall Study STARTED	64
Overall Study COMPLETED	62
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	FLUAD Participants received a single intramuscular (IM) dose of 0.5 milliliter (mL) of FLUAD containing 15μg each of the three influenza antigens into the deltoid region of the non-dominant arm during the vaccination visit, according to the study protocol until Day 22.
Overall Study Lost to Follow-up	2

Baseline Characteristics

Study to Evaluate Safety and Immunogenicity of Sub-unit Adjuvanted Influenza Vaccine Administered to Elderly Subjects, Formulation 2010-2011

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FLUAD n=64 Participants Participants received a single IM dose of 0.5 mL of FLUAD containing 15μg each of the three influenza antigens into the deltoid region of the non-dominant arm during the vaccination visit, according to the study protocol until Day 22.
Age, Continuous	73.3 Years STANDARD_DEVIATION 5.1 • n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants
Sex: Female, Male Male	30 Participants n=5 Participants

PRIMARY outcome

Timeframe: day 22

Population: Per protocol (PP) analysis set included all enrolled participants who had received the vaccine, provided evaluable serum samples before and after vaccination, and had no major protocol violation.

Outcome measures

Outcome measures
Measure	FLUAD n=62 Participants Participants received a single IM dose of 0.5 mL of FLUAD containing 15μg each of the three influenza antigens into the deltoid region of the non-dominant arm during the vaccination visit, according to the study protocol until Day 22.
Percentage of Participants Who Achieved Seroconversion or Significant Increase in Single Radial Hemolysis (SRH) Area Against Each of Three Vaccine Strains After One Vaccination of FLUAD A/H1N1	45 Percentage of participants Interval 32.0 to 58.0
Percentage of Participants Who Achieved Seroconversion or Significant Increase in Single Radial Hemolysis (SRH) Area Against Each of Three Vaccine Strains After One Vaccination of FLUAD A/H3N2	61 Percentage of participants Interval 48.0 to 73.0
Percentage of Participants Who Achieved Seroconversion or Significant Increase in Single Radial Hemolysis (SRH) Area Against Each of Three Vaccine Strains After One Vaccination of FLUAD B	27 Percentage of participants Interval 17.0 to 40.0

PRIMARY outcome

Timeframe: day 22

Population: Analysis was done using the PP dataset.

Geometric mean ratio (GMR) of participants was calculated as the ratio of post-vaccination to pre-vaccination SRH geometric mean areas (GMAs), directed against each of the three vaccine strains, three weeks after FLUAD vaccination (day 22). The CHMP criterion was met if the geometric mean increase (GMR, day 22/day 1) in SRH antibody area is \>2.0 (≥65 years).

Outcome measures

Outcome measures
Measure	FLUAD n=62 Participants Participants received a single IM dose of 0.5 mL of FLUAD containing 15μg each of the three influenza antigens into the deltoid region of the non-dominant arm during the vaccination visit, according to the study protocol until Day 22.
Geometric Mean Ratio of Participants Against Each of the Three Vaccine Strains After One Vaccination of FLUAD A/H1N1	1.96 Ratio Interval 1.59 to 2.42
Geometric Mean Ratio of Participants Against Each of the Three Vaccine Strains After One Vaccination of FLUAD A/H3N2	1.88 Ratio Interval 1.64 to 2.16
Geometric Mean Ratio of Participants Against Each of the Three Vaccine Strains After One Vaccination of FLUAD B	1.32 Ratio Interval 1.22 to 1.43

PRIMARY outcome

Timeframe: day 22

Population: Analysis was done using the PP dataset.

Immunogenicity was measured as the percentage of participants achieving SRH area ≥25 mm2 against each of the three vaccine strains at baseline (day 1) and three weeks after FLUAD vaccination (day 22). This criterion is met according to CHMP guideline if percentage of participants achieving SRH area ≥25 mm2 is 60% (≥65 years).

Outcome measures

Outcome measures
Measure	FLUAD n=62 Participants Participants received a single IM dose of 0.5 mL of FLUAD containing 15μg each of the three influenza antigens into the deltoid region of the non-dominant arm during the vaccination visit, according to the study protocol until Day 22.
Percentage of Participants Who Achieved SRH Area ≥25mm2 Against Each of the Three Vaccine Strains After One Vaccination of FLUAD A/H1N1	97 Percentage of participants Interval 89.0 to 100.0
Percentage of Participants Who Achieved SRH Area ≥25mm2 Against Each of the Three Vaccine Strains After One Vaccination of FLUAD A/H3N2	71 Percentage of participants Interval 58.0 to 82.0
Percentage of Participants Who Achieved SRH Area ≥25mm2 Against Each of the Three Vaccine Strains After One Vaccination of FLUAD B	100 Percentage of participants Interval 94.0 to 100.0

SECONDARY outcome

Timeframe: 1 to 4 days post-vaccination

Population: Analysis was done using the safety dataset; all participants exposed and who had post-baseline safety data were included in the safety analysis.

Safety was assessed for all participants who reported solicited local and systemic reactions from Day 1 up to and including Day 4 after the FLUAD vaccination in accordance with available safety data on influenza vaccines.

Outcome measures

Outcome measures
Measure	FLUAD n=64 Participants Participants received a single IM dose of 0.5 mL of FLUAD containing 15μg each of the three influenza antigens into the deltoid region of the non-dominant arm during the vaccination visit, according to the study protocol until Day 22.
Number of Participants Who Reported Solicited Local and Systemic Reactions Injection site ecchymosis (N= 62)	2 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Injection site erythema (N= 62)	4 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Injection site induration (N= 62)	2 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Injection site swelling (N= 62)	0 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Injection site pain (N= 62)	15 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Chills/Shivering (N= 62)	2 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Malaise (N= 62)	2 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Myalgia (N= 62)	7 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Arthralgia (N= 62)	4 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Headache (N= 62)	5 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Sweating (N= 62)	7 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Fatigue (N= 62)	5 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Fever (≥38°C) (N= 59)	0 Number of participants

Adverse Events

FLUAD

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	FLUAD n=64 participants at risk Participants received a single IM dose of 0.5 mL of FLUAD containing 15μg each of the three influenza antigens into the deltoid region of the non-dominant arm during the vaccination visit, according to the study protocol until Day 22.
General disorders Fatigue	3.1% 2/64 • From Day 1 through Day 22. Adverse events other than local and systemic reactions or solicited reactions lasting longer than 4 days after vaccination were documented during the study period. Analysis was done using the safety dataset; all participants exposed and who had post-baseline safety data were included in the safety analysis.
General disorders Malaise	1.6% 1/64 • From Day 1 through Day 22. Adverse events other than local and systemic reactions or solicited reactions lasting longer than 4 days after vaccination were documented during the study period. Analysis was done using the safety dataset; all participants exposed and who had post-baseline safety data were included in the safety analysis.
Infections and infestations Bronchitis	1.6% 1/64 • From Day 1 through Day 22. Adverse events other than local and systemic reactions or solicited reactions lasting longer than 4 days after vaccination were documented during the study period. Analysis was done using the safety dataset; all participants exposed and who had post-baseline safety data were included in the safety analysis.
Musculoskeletal and connective tissue disorders Arthralgia	1.6% 1/64 • From Day 1 through Day 22. Adverse events other than local and systemic reactions or solicited reactions lasting longer than 4 days after vaccination were documented during the study period. Analysis was done using the safety dataset; all participants exposed and who had post-baseline safety data were included in the safety analysis.
Nervous system disorders Headache	3.1% 2/64 • From Day 1 through Day 22. Adverse events other than local and systemic reactions or solicited reactions lasting longer than 4 days after vaccination were documented during the study period. Analysis was done using the safety dataset; all participants exposed and who had post-baseline safety data were included in the safety analysis.
Nervous system disorders Paraesthesia	1.6% 1/64 • From Day 1 through Day 22. Adverse events other than local and systemic reactions or solicited reactions lasting longer than 4 days after vaccination were documented during the study period. Analysis was done using the safety dataset; all participants exposed and who had post-baseline safety data were included in the safety analysis.

Additional Information

Posting Director

Novartis Vaccines and Diagnostics

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreement with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publications of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER