Trial Outcomes & Findings for Safety and Immunogenicity of Surface Antigen, Inactivated, Adjuvanted With MF59C.1 Influenza Vaccine, Formulation 2008-2009 (NCT NCT00734734)

Last Updated: 2016-01-28

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 21), 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 21

Results posted on

2016-01-28

Participant Flow

Overall, 64 participants ≥65 years of age were enrolled at 2 sites in Italy.

Blood samples for the determination of antibody titers were drawn on Day 0 prior to vaccination.

Participant milestones

Participant milestones
Measure	FLUAD Participants received a single intramuscular (IM) 0.5 milliliter (mL) dose of FLUAD, a trivalent subunit inactivated adjuvanted with MF59C.1 influenza vaccine recommended for the NH 2008/2009 influenza season into the deltoid region of the non-dominant arm on Day 0 and were assessed until Day 21.
Overall Study STARTED	64
Overall Study COMPLETED	64
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Immunogenicity of Surface Antigen, Inactivated, Adjuvanted With MF59C.1 Influenza Vaccine, Formulation 2008-2009

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FLUAD n=64 Participants Participants received a single IM 0.5 mL dose of FLUAD, a trivalent subunit inactivated adjuvanted with MF59C.1 influenza vaccine recommended for the NH 2008/2009 influenza season into the deltoid region of the non-dominant arm on Day 0 and were assessed until Day 21.
Age, Continuous	73.1 Years STANDARD_DEVIATION 4.8 • n=5 Participants
Sex: Female, Male Female	32 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants

PRIMARY outcome

Timeframe: day 21

Population: Per protocol (PP) analysis set included all enrolled participants who had received the relevant dose of vaccine correctly on Day 0, provided evaluable serum samples with the relevant time windows, and had no major protocol violations.

Outcome measures

Outcome measures
Measure	FLUAD n=64 Participants Participants received a single IM 0.5 mL dose of FLUAD, a trivalent subunit inactivated adjuvanted with MF59C.1 influenza vaccine recommended for the NH 2008/2009 influenza season into the deltoid region of the non-dominant arm on Day 0 and were assessed until Day 21.
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	38 Percentage of participants Interval 26.0 to 50.0
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	55 Percentage of participants Interval 42.0 to 67.0
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	42 Percentage of participants Interval 30.0 to 55.0

PRIMARY outcome

Timeframe: day 21

Population: Analysis was done using PP set.

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 21). The CHMP criterion was met if the geometric mean increase (GMR, day 21/day 0) in SRH antibody area is \>2.0 (≥65 years).

Outcome measures

Outcome measures
Measure	FLUAD n=64 Participants Participants received a single IM 0.5 mL dose of FLUAD, a trivalent subunit inactivated adjuvanted with MF59C.1 influenza vaccine recommended for the NH 2008/2009 influenza season into the deltoid region of the non-dominant arm on Day 0 and were assessed until Day 21.
Geometric Mean Ratio of Participants Against Each of the Three Vaccine Strains After One Vaccination of FLUAD A/H1N1	1.87 Ratio Interval 1.5 to 2.33
Geometric Mean Ratio of Participants Against Each of the Three Vaccine Strains After One Vaccination of FLUAD A/H3N2	3.74 Ratio Interval 2.73 to 5.11
Geometric Mean Ratio of Participants Against Each of the Three Vaccine Strains After One Vaccination of FLUAD B	2.38 Ratio Interval 1.81 to 3.13

PRIMARY outcome

Timeframe: day 21

Population: Analysis was done using PP set.

Immunogenicity was measured as the percentage of participants achieving SRH area ≥25 mm2 against each of the three vaccine strains at baseline (day 0) and three weeks after FLUAD vaccination (day 21). 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=64 Participants Participants received a single IM 0.5 mL dose of FLUAD, a trivalent subunit inactivated adjuvanted with MF59C.1 influenza vaccine recommended for the NH 2008/2009 influenza season into the deltoid region of the non-dominant arm on Day 0 and were assessed until Day 21.
Percentage of Participants Who Achieved SRH Area ≥25mm2 Against Each of the Three Vaccine Strains After One Vaccination of FLUAD A/H1N1	89 Percentage of participants Interval 79.0 to 95.0
Percentage of Participants Who Achieved SRH Area ≥25mm2 Against Each of the Three Vaccine Strains After One Vaccination of FLUAD A/H3N2	75 Percentage of participants Interval 63.0 to 85.0
Percentage of Participants Who Achieved SRH Area ≥25mm2 Against Each of the Three Vaccine Strains After One Vaccination of FLUAD B	80 Percentage of participants Interval 68.0 to 89.0

PRIMARY outcome

Timeframe: 0 to 3 days post-vaccination

Population: Analysis was done using the safety dataset; participants in the exposed population who provided post-vaccination safety data.

Safety was assessed for participants who reported solicited local and systemic reactions from day 0 up to and including day 3 after the FLUAD vaccination.

Outcome measures

Outcome measures
Measure	FLUAD n=64 Participants Participants received a single IM 0.5 mL dose of FLUAD, a trivalent subunit inactivated adjuvanted with MF59C.1 influenza vaccine recommended for the NH 2008/2009 influenza season into the deltoid region of the non-dominant arm on Day 0 and were assessed until Day 21.
Number of Participants Who Reported Solicited Local and Systemic Reactions Injection site ecchymosis (N= 59)	0 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Injection site erythema (N= 64)	10 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Injection site induration (N= 64)	2 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Injection site swelling (N= 59)	0 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Injection site pain (N= 64)	11 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Chills shivering (N= 64)	0 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Malaise (N= 64)	0 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Myalgia (N= 64)	1 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Arthralgia (N= 64)	0 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Headache (N= 64)	2 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Sweating (N= 64)	1 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Fatigue (N= 64)	2 Number of participants
Number of Participants Who Reported Solicited Local and Systemic Reactions Fever (≥38°C) (N= 64)	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 0.5 mL dose of FLUAD, a trivalent subunit inactivated adjuvanted with MF59C.1 influenza vaccine recommended for the NH 2008/2009 influenza season into the deltoid region of the non-dominant arm on Day 0 and were assessed until Day 21.
General disorders Induration	1.6% 1/64 • From Day 0 through Day 21. Adverse events other than local and systemic reactions or solicited reactions lasting longer than 3 days after vaccination were documented during the study period. Analysis was done using the safety dataset; participants in the exposed population who provided post-vaccination safety data.
General disorders Injection site erythema	1.6% 1/64 • From Day 0 through Day 21. Adverse events other than local and systemic reactions or solicited reactions lasting longer than 3 days after vaccination were documented during the study period. Analysis was done using the safety dataset; participants in the exposed population who provided post-vaccination safety data.
Musculoskeletal and connective tissue disorders Myalgia	1.6% 1/64 • From Day 0 through Day 21. Adverse events other than local and systemic reactions or solicited reactions lasting longer than 3 days after vaccination were documented during the study period. Analysis was done using the safety dataset; participants in the exposed population who provided post-vaccination safety data.
Nervous system disorders Headache	1.6% 1/64 • From Day 0 through Day 21. Adverse events other than local and systemic reactions or solicited reactions lasting longer than 3 days after vaccination were documented during the study period. Analysis was done using the safety dataset; participants in the exposed population who provided post-vaccination safety data.
Skin and subcutaneous tissue disorders Erythema	3.1% 2/64 • From Day 0 through Day 21. Adverse events other than local and systemic reactions or solicited reactions lasting longer than 3 days after vaccination were documented during the study period. Analysis was done using the safety dataset; participants in the exposed population who provided post-vaccination safety data.
Skin and subcutaneous tissue disorders Hyperhidrosis	1.6% 1/64 • From Day 0 through Day 21. Adverse events other than local and systemic reactions or solicited reactions lasting longer than 3 days after vaccination were documented during the study period. Analysis was done using the safety dataset; participants in the exposed population who provided post-vaccination safety data.

Additional Information

Posting Director

Novartis Vaccines and Diagnostics S.r.l

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