Seasonal Influenza
Conditions
Keywords
Seasonal Influenza, vaccine
Brief summary
This study will evaluate the safety and immunogenicity of a sub-unit, adjuvanted Influenza Vaccine Administered to Elderly Subjects.
Interventions
BIOLOGICALSeasonal Influenza Vaccine
This phase II is performed as a multicenter study in elderly subjects. Enrolled subjects received one single IM dose of trivalent subunit inactivated adjuvanted flu vaccine during the vaccination visit, according to the study protocol (follow-up period: until day 22) .
Sponsors
Novartis Vaccines
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: * Males and females volunteers of 65 years of age or older, mentally competent, willing and able to give written informed consent prior to study entry. * Individuals able to comply with all the study requirements. * Individuals in good health as determined by the outcome of medical history, physical examination and clinical judgment of the investigator. * Written informed consent must be obtained for all the subjects before enrollment into the study after the nature of the study has been explained. Key
Exclusion criteria
* Individuals with any serious chronic or acute disease. * Individuals with history of any anaphylactic reaction and/or serious allergic reaction following a vaccination. * Individuals with known or suspected impairment/alteration of immune function. * Individuals with known or suspected history of drug or alcohol abuse. * Individuals with a bleeding diathesis or conditions associated with prolonged bleeding time that in the investigator's opinion would interfere with the safety of the subject. * Individuals within the past 6 months, they have: had any seasonal or pandemic laboratory confirmed influenza disease; received any seasonal or pandemic influenza vaccine. * Individuals with any acute or chronic infections requiring systemic antibiotic treatment or antiviral therapy within the last 7 days. * Individuals that have experienced fever (i.e., axillary temperature ≥38°C) within the last 3 days of intended study vaccination. * Individuals participating in any clinical trial with another investigational product 4 weeks prior to first study visit or intent to participate in another clinical study at any time during the conduct of this study. * Individuals who received any other vaccines within 4 weeks prior to enrollment in this study or who are planning to receive any vaccine within 4 weeks from the study vaccines. * Individuals who are part of study personnel or close family members conducting this study. * BMI \> 35 kg/m2.
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 22 | 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). |
| Geometric Mean Ratio of Participants Against Each of the Three Vaccine Strains After One Vaccination of FLUAD | day 22 | 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). |
| Percentage of Participants Who Achieved SRH Area ≥25mm2 Against Each of the Three Vaccine Strains After One Vaccination of FLUAD | day 22 | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Reported Solicited Local and Systemic Reactions | 1 to 4 days post-vaccination | Safety was assessed for participants who reported solicited local and systemic reactions from day 1 up to and including day 4 after the FLUAD vaccination. |
Countries
Italy
Participant flow
Recruitment details
Overall, 63 participants were ≥65 years of age were enrolled at 4 sites in Italy.
Pre-assignment details
Blood sample for immunogenicity assays were collected before vaccination (Day 1) and after 21 Days.
Participants by arm
| Arm | Count |
|---|---|
| FLUAD 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. | 63 |
| Total | 63 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Premature Withdrawal | 1 |
Baseline characteristics
| Characteristic | FLUAD |
|---|---|
| Age, Continuous | 73.2 Years STANDARD_DEVIATION 5.2 |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 6 / 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 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).
Time frame: day 22
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 (N= 62) | 2.54 Ratio |
| FLUAD | Geometric Mean Ratio of Participants Against Each of the Three Vaccine Strains After One Vaccination of FLUAD | A/H3N2 (N= 62) | 1.9 Ratio |
| FLUAD | Geometric Mean Ratio of Participants Against Each of the Three Vaccine Strains After One Vaccination of FLUAD | B (N= 62) | 1.36 Ratio |
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 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).
Time frame: day 22
Population: Per protocol (PP) analysis set included all enrolled participants who had correctly received the vaccine, provided evaluable serum samples before and after vaccination, 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 | B (N= 62) | 26 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/H1N1 (N= 62) | 69 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 (N= 62) | 50 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 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).
Time frame: day 22
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 (N= 62) | 89 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 (N= 62) | 69 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 (N= 62) | 94 Percentage of participants |
Secondary
Number of Participants Who Reported Solicited Local and Systemic Reactions
Safety was assessed for participants who reported solicited local and systemic reactions from day 1 up to and including day 4 after the FLUAD vaccination.
Time frame: 1 to 4 days post-vaccination
Population: Analysis was done using the safety dataset; participants who received study vaccination and who provided post-vaccination safety data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Sweating (N= 62) | 1 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Arthralgia (N= 62) | 4 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Headache (N= 62) | 4 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Fatigue (N= 62) | 2 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Fever (≥38°C) (N= 61) | 0 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Injection site ecchymosis (N= 62) | 3 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Injection site erythema (N= 62) | 7 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Injection site induration (N= 62) | 4 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Injection site swelling (N= 62) | 7 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Injection site pain (N= 62) | 21 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Chills Shivering (N= 62) | 4 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Malaise (N= 62) | 3 Number of participants |
| FLUAD | Number of Participants Who Reported Solicited Local and Systemic Reactions | Myalgia (N= 62) | 6 Number of participants |