Seasonal Influenza
Conditions
Keywords
Influenza vaccine
Brief summary
This is a trial for annual registration of the updated seasonal influenza vaccine formulation.
Interventions
BIOLOGICALSeasonal Influenza Vaccine (MF59C.1)
1 dose of a surface antigen, inactivated, adjuvanted with MF59C.1, seasonal influenza vaccine, formulation 2009-2010
Sponsors
Novartis Vaccines
Novartis
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: * Subjects of 65 years of age or older * Mentally competent * Willing and able to give written informed consent prior to study entry * Able to comply with all the study requirements * In general good health Key
Exclusion criteria
* Any serious chronic or acute disease disease * History of any anaphylactic reaction and/or serious allergic reaction following a vaccination * A proven hypersensitivity to any component of the study vaccine * Known or suspected (or have a high risk of developing) impairment/alteration of immune function (excluding that normally associated with advanced age) * Bleeding diathesis or conditions associated with prolonged bleeding time that in the investigator's opinion would interfere with the safety of the subject * Within the past 12 months, participants had received more than one injection of influenza vaccine * Within the past 6 months, participants had laboratory confirmed influenza disease or received influenza vaccine
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Day 21 | 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). |
| Geometric Mean Ratio of Participants Against Each of the Three Vaccine Strains After One Vaccination of FLUAD | day 21 | 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). |
| Percentage of Participants Who Achieved SRH Area ≥25mm2 Against Each of the Three Vaccine Strains After One Vaccination of FLUAD | day 21 | 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). |
| Number of Participants Who Reported Solicited Local and Systemic Reactions | 0-3 days post-vaccination | 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. |
Countries
Italy
Participant flow
Recruitment details
Overall, 63 participants ≥65 years of age were enrolled at 2 sites in Italy.
Pre-assignment details
Blood samples for the determination of antibody titers were drawn on Day 0 prior to vaccination.
Participants by arm
| Arm | Count |
|---|---|
| FLUAD 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 2009/2010 influenza season, into the deltoid region of the non-dominant arm on Day 0 and were assessed until Day 21. | 63 |
| Total | 63 |
Baseline characteristics
| Characteristic | FLUAD |
|---|---|
| Age, Continuous | 72.9 Years STANDARD_DEVIATION 6 |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 2 / 63 |
| serious Total, serious adverse events | 0 / 63 |
Outcome results
Primary
Geometric Mean Ratio of Participants Against Each of the Three Vaccine Strains After One Vaccination of FLUAD
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).
Time frame: day 21
Population: Analysis was done using PP set.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| FLUAD | Geometric Mean Ratio of Participants Against Each of the Three Vaccine Strains After One Vaccination of FLUAD | A/H1N1 | 1.55 Ratio |
| FLUAD | Geometric Mean Ratio of Participants Against Each of the Three Vaccine Strains After One Vaccination of FLUAD | A/H3N2 | 1.53 Ratio |
| FLUAD | Geometric Mean Ratio of Participants Against Each of the Three Vaccine Strains After One Vaccination of FLUAD | B | 1.59 Ratio |
Primary
Number of Participants Who Reported Solicited Local and Systemic Reactions
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.
Time frame: 0-3 days post-vaccination
Population: Analysis was done using the safety dataset; participants in the exposed population who provided post-vaccination safety data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Fatigue | 1 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Myalgia | 0 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Injection site ecchymosis | 2 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Injection site erythema | 8 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Injection site induration | 3 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Injection site swelling | 6 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Injection site pain | 9 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Chills Shivering | 1 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Malaise | 1 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Arthralgia | 1 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Headache | 5 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Sweating | 0 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Fever (≥38°C) | 0 Number of participants |
Primary
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
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).
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FLUAD | 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 | 43 Percentage of participants |
| FLUAD | 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 | 46 Percentage of participants |
| FLUAD | 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 | 43 Percentage of participants |
Primary
Percentage of Participants Who Achieved SRH Area ≥25mm2 Against Each of the Three Vaccine Strains After One Vaccination of FLUAD
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).
Time frame: day 21
Population: Analysis was done using PP set.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FLUAD | Percentage of Participants Who Achieved SRH Area ≥25mm2 Against Each of the Three Vaccine Strains After One Vaccination of FLUAD | A/H1N1 | 93 Percentage of participants |
| FLUAD | Percentage of Participants Who Achieved SRH Area ≥25mm2 Against Each of the Three Vaccine Strains After One Vaccination of FLUAD | A/H3N2 | 93 Percentage of participants |
| FLUAD | Percentage of Participants Who Achieved SRH Area ≥25mm2 Against Each of the Three Vaccine Strains After One Vaccination of FLUAD | B | 98 Percentage of participants |