Influenza
Conditions
Keywords
Influenza, Flu, Cell Culture-Derived, Egg-Derived, Healthy Adults, Efficacy, Safety, Immunogenicity, Trivalent, Inactivated, Influenza-Like Illness, Vaccination
Brief summary
The present study will evaluate clinical efficacy, safety, tolerability and immunogenicity of both Novartis Vaccines' cell-derived influenza vaccine and egg-derived influenza vaccine in healthy adults 18 to 49 years of age.
Interventions
BIOLOGICALPlacebo
One dose (0.5 mL) of phosphate buffered solution.
BIOLOGICALCell culture-derived influenza vaccine
One dose (0.5 mL) of cell culture-derived influenza vaccine, administered in the deltoid muscle.
BIOLOGICALEgg-derived influenza virus vaccine
One dose (0.5 mL) of the trivalent egg-derived influenza virus vaccine, administered in the deltoid muscle.
Sponsors
Novartis Vaccines
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
1. subjects 18 to 49 years of age; 2. in good health as determined by medical history and physical examination; 3. able and willing to provide written informed consent prior to any study procedure; 4. able to comply with all study procedures, including availability and willingness to be actively followed throughout the ensuing influenza season with weekly telephone calls and to comply with the need for prompt collection of nasal and throat specimens in the event of influenza symptoms.
Exclusion criteria
1. history of anaphylaxis or serious reaction after administration of any vaccine, or hypersensitivity to eggs, egg protein, chicken feathers, influenza viral protein, neomycin, kanamycin, or any other vaccine component, chemically related substance, or component of the potential packaging materials; 2. any health condition for which the inactivated vaccine is recommended by the Advisory Committee on Immunization Practices (ACIP) including chronic diseases of the pulmonary or cardiovascular systems (including asthma), chronic metabolic diseases (including diabetes), renal dysfunction, hemoglobinopathies, immune deficiency disease (including HIV infection) or on-going immunosuppressive therapy; 3. employment in professions prone to influenza transmission to or from high-risk populations (this exclusion specifically includes nurses, physicians, all other healthcare workers with direct patient contact; and police, fire, and rescue personnel); or living in the same household as an immunocompromised person; 4. history of Guillain-Barré syndrome; 5. bleeding diathesis; 6. receipt of another investigational agent within 90 days prior to enrollment in the study or before completion of the safety follow-up period in another study, whichever is longer, and unwilling to refuse participation in another clinical study through the end of the study; 7. receipt of another vaccine within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to Visit 1; 8. laboratory-confirmed influenza disease within 6 months prior to Visit 1; 9. receipt of an influenza vaccine within 6 months prior to Visit 1 or plans to receive influenza vaccine outside of this study; 10. experienced a temperature (≥100.0°F / ≥37.8°C) and/or any acute illness within 3 days prior to study vaccination; 11. pregnant or breast-feeding female; 12. if female of childbearing potential and sexually active, has not used any of the birth control methods detailed in the section entitled Females of Childbearing Potential for at least 2 months prior to study entry; 13. if female of childbearing potential and sexually active, refusal to use a reliable contraceptive method as detailed in the section entitled Females of Childbearing Potential during the first 3 weeks after vaccination; 14. research staff directly involved with the clinical study or family members or household members of research staff. Research staff are individuals with direct or indirect contact with study subjects, or study site personnel who have access to any study documents containing subject information. This would include receptionists, persons scheduling appointments or making screening calls, regulatory specialists, laboratory technicians, etc.; 15. any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives or with the safety of the study subject.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Culture-Confirmed Influenza Illness Caused by Vaccine-like Strains | 6 Months | The vaccine efficacy of CCI and IVV vaccines was estimated relative to Placebo group as the number of subjects prevented against virus-confirmed symptomatic influenza illness caused by each of three vaccine-like virus strains. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Subjects With Influenza Caused by Vaccine-like and Non-vaccine-like Strains | 6 Months | The vaccine efficacy of CCI and IVV vaccines was estimated relative to placebo as the number of subjected prevented against virus-confirmed symptomatic influenza A or B illness caused by vaccine-like and non-vaccine-like strains. |
| Influenza-Associated Days in Bed, All Subjects | 6 Months | The number of subjects in this analysis included all subjects in the per protocol efficacy population. |
| Influenza-Associated Days in Bed, Subset of Subjects With Virus-Confirmed- Influenza | 6 Months | The analysis was done among the subset of subjects in the per protocol efficacy population who had culture-confirmed influenza. |
| Number Of Medical Visits (Inpatient and Outpatient) Due to Influenza Illness or Symptoms of Influenza, All Subjects | 6 Months | The number of subjects in this analysis included all subjects in the per protocol efficacy population. |
| Number of Medical Visits (Inpatient and Outpatient), Subset of Subjects With Virus-Confirmed-Influenza | 6 Months | The analysis was done among the subset of subjects in the per protocol efficacy population who had culture-confirmed influenza. |
| Number of Subjects With Culture-confirmed Influenza Illness Caused by Non-Vaccine Like Strains | 6 Months | The vaccine efficacy of CCI and IVV vaccines was estimated relative to placebo group as the number of subjects prevented against virus-confirmed symptomatic influenza A or B illness caused by non-vaccine-like strains. |
| Number of Days of Usual Activity (i.e. Job, School,Household/Family/Community Activities) Lost, Subset of Subjects With Virus-Confirmed-Influenza | 6 Months | The analysis was done among the subset of subjects in the per protocol efficacy population who had culture-confirmed influenza. |
| Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | Before vaccination (day 1) and three weeks after vaccination (day 22) | Immunogenicity was measured as the percentage of subjects achieving HI titers ≥40 at baseline (day 1) and three weeks after (day 22) one vaccination of either cell-culture or egg-derived vaccine or placebo for each of the three influenza vaccine strains (A/H1N1, A/H3N2 and B), evaluated using hemagglutination inhibition (HI) egg-derived antigen assay. This criterion is met according to US (CBER) guideline if the lower limit of the two-sided 95% CI for the percentage of subjects achieving HI titers ≥40 is ≥70%. |
| Percentages of Subjects Achieving Seroconversion After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | Three weeks after vaccination (day 22) | As per the CBER guideline, seroconversion is defined as the percentage of subjects with a prevaccination HI titer \<10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, a ≥4-fold increase in postvaccination HI antibody titer. According to CBER criteria, the lower limit of the two-sided 95% CI for the percentage of subjects achieving seroconversion for HI antibody titer at day 22 met exceeded 40%. |
| Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Up to 7 days post vaccination | The solicited local and systemic reactogenicity were collected up to 7 days after vaccination for all three vaccine groups. |
| Number of Days of Usual Activity (i.e. Job, School,Household/Family/Community Activities) Lost Due to Influenza Disease, All Subjects | 6 Months | The number of subjects in this analysis included all subjects in the per protocol efficacy population. |
Countries
Finland, Poland, United States
Participant flow
Recruitment details
Participants were enrolled at multiple centres in the US, Poland and Finland.
Pre-assignment details
All enrolled subjects were included in the trial.
Participants by arm
| Arm | Count |
|---|---|
| CCI Vaccine One dose of cell culture-derived influenza vaccine. | 3,828 |
| IVV Vaccine One dose of the trivalent egg-derived influenza virus vaccine. | 3,676 |
| Placebo One dose of phosphate buffered solution (PBS). | 3,900 |
| Total | 11,404 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Death | 2 | 1 | 1 |
| Overall Study | Inappropriate enrollment | 3 | 6 | 3 |
| Overall Study | Lost to Follow-up | 175 | 143 | 170 |
| Overall Study | Protocol Violation | 4 | 5 | 6 |
| Overall Study | Unable to classify | 9 | 4 | 3 |
| Overall Study | Withdrawal by Subject | 12 | 7 | 5 |
Baseline characteristics
| Characteristic | CCI Vaccine | IVV Vaccine | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 32.7 years STANDARD_DEVIATION 10.1 | 33.0 years STANDARD_DEVIATION 10.2 | 32.7 years STANDARD_DEVIATION 10.2 | 32.8 years STANDARD_DEVIATION 10.2 |
| Sex/Gender, Customized Female | 2088 Subjects | 2026 Subjects | 2176 Subjects | 6290 Subjects |
| Sex/Gender, Customized Male | 1740 Subjects | 1649 Subjects | 1722 Subjects | 5111 Subjects |
| Sex/Gender, Customized Not Available | 0 Subjects | 1 Subjects | 2 Subjects | 3 Subjects |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 1,949 / 3,813 | 1,703 / 3,669 | 1,387 / 3,894 |
| serious Total, serious adverse events | 42 / 3,813 | 35 / 3,669 | 38 / 3,894 |
Outcome results
Primary
Number of Subjects With Culture-Confirmed Influenza Illness Caused by Vaccine-like Strains
The vaccine efficacy of CCI and IVV vaccines was estimated relative to Placebo group as the number of subjects prevented against virus-confirmed symptomatic influenza illness caused by each of three vaccine-like virus strains.
Time frame: 6 Months
Population: Analysis was performed on per protocol (PP) efficacy population i.e. the subjects in the exposed efficacy population who correctly received the vaccine and provided evaluable swab samples at the relevant time points.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CCI Vaccine | Number of Subjects With Culture-Confirmed Influenza Illness Caused by Vaccine-like Strains | Overall | 7 Subjects |
| CCI Vaccine | Number of Subjects With Culture-Confirmed Influenza Illness Caused by Vaccine-like Strains | A/Wisconsin/67/2005 (H3N2)-like | 2 Subjects |
| CCI Vaccine | Number of Subjects With Culture-Confirmed Influenza Illness Caused by Vaccine-like Strains | A/Solomon Islands/3/2006 (H1N1)-like | 5 Subjects |
| CCI Vaccine | Number of Subjects With Culture-Confirmed Influenza Illness Caused by Vaccine-like Strains | B/Malaysia/2506/2004-like | 0 Subjects |
| IVV Vaccine | Number of Subjects With Culture-Confirmed Influenza Illness Caused by Vaccine-like Strains | B/Malaysia/2506/2004-like | 0 Subjects |
| IVV Vaccine | Number of Subjects With Culture-Confirmed Influenza Illness Caused by Vaccine-like Strains | Overall | 9 Subjects |
| IVV Vaccine | Number of Subjects With Culture-Confirmed Influenza Illness Caused by Vaccine-like Strains | A/Solomon Islands/3/2006 (H1N1)-like | 8 Subjects |
| IVV Vaccine | Number of Subjects With Culture-Confirmed Influenza Illness Caused by Vaccine-like Strains | A/Wisconsin/67/2005 (H3N2)-like | 1 Subjects |
| Placebo | Number of Subjects With Culture-Confirmed Influenza Illness Caused by Vaccine-like Strains | B/Malaysia/2506/2004-like | 1 Subjects |
| Placebo | Number of Subjects With Culture-Confirmed Influenza Illness Caused by Vaccine-like Strains | A/Wisconsin/67/2005 (H3N2)-like | 0 Subjects |
| Placebo | Number of Subjects With Culture-Confirmed Influenza Illness Caused by Vaccine-like Strains | A/Solomon Islands/3/2006 (H1N1)-like | 43 Subjects |
| Placebo | Number of Subjects With Culture-Confirmed Influenza Illness Caused by Vaccine-like Strains | Overall | 44 Subjects |
Comparison: Vaccine efficacy (VE) of CCI vaccine vs. Placebo (Overall)~Simultaneous one-sided 97.5% confidence interval (CI) for the VE of CCI vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: <0.001Sidak-corrected score CI
Comparison: Vaccine efficacy (VE) of CCI vaccine vs. Placebo for A/H1N1 strain~Simultaneous one-sided 97.5% confidence interval (CI) for the VE of CCI vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: <0.001Sidak-corrected score CI
Comparison: Vaccine efficacy (VE) of CCI vaccine vs. Placebo for A/H3N2 strain. Simultaneous one-sided 97.5% confidence interval (CI) for the VE of CCI vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: 0.999Sidak-corrected score CI
Comparison: Vaccine efficacy (VE) of CCI vaccine vs. Placebo for B strain~Simultaneous one-sided 97.5% confidence interval (CI) for the VE of CCI vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: 0.394Sidak-corrected score CI
Comparison: Vaccine efficacy (VE) of IVV vaccine vs. Placebo (Overall)~Simultaneous one-sided 97.5% confidence interval (CI) for the VE of IVV vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: 0.004Sidak-corrected score CI
Comparison: Vaccine efficacy (VE) of IVV vaccine vs. Placebo for A/H1N1 strain~Simultaneous one-sided 97.5% confidence interval (CI) for the VE of IVV vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: 0.002Sidak-corrected score CI
Comparison: Vaccine efficacy (VE) of IVV vaccine vs. Placebo for A/H3N2 strain. Simultaneous one-sided 97.5% confidence interval (CI) for the VE of IVV vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: 0.992Sidak-corrected score CI
Comparison: Vaccine efficacy (VE) of IVV vaccine vs. Placebo for B strain~Simultaneous one-sided 97.5% confidence interval (CI) for the VE of IVV vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: 0.4Sidak-corrected score CI
Secondary
Influenza-Associated Days in Bed, All Subjects
The number of subjects in this analysis included all subjects in the per protocol efficacy population.
Time frame: 6 Months
Population: Analysis was done on the PP efficacy population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CCI Vaccine | Influenza-Associated Days in Bed, All Subjects | 0.04 Number of Days | Standard Deviation 0.496 |
| IVV Vaccine | Influenza-Associated Days in Bed, All Subjects | 0.04 Number of Days | Standard Deviation 0.404 |
| Placebo | Influenza-Associated Days in Bed, All Subjects | 0.12 Number of Days | Standard Deviation 0.777 |
Secondary
Influenza-Associated Days in Bed, Subset of Subjects With Virus-Confirmed- Influenza
The analysis was done among the subset of subjects in the per protocol efficacy population who had culture-confirmed influenza.
Time frame: 6 Months
Population: Analysis was done on PP efficacy population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CCI Vaccine | Influenza-Associated Days in Bed, Subset of Subjects With Virus-Confirmed- Influenza | 3.9 Number of Days | Standard Deviation 2.62 |
| IVV Vaccine | Influenza-Associated Days in Bed, Subset of Subjects With Virus-Confirmed- Influenza | 2.9 Number of Days | Standard Deviation 1.98 |
| Placebo | Influenza-Associated Days in Bed, Subset of Subjects With Virus-Confirmed- Influenza | 3.4 Number of Days | Standard Deviation 2.4 |
Secondary
Number of Days of Usual Activity (i.e. Job, School,Household/Family/Community Activities) Lost Due to Influenza Disease, All Subjects
The number of subjects in this analysis included all subjects in the per protocol efficacy population.
Time frame: 6 Months
Population: Analysis was done on PP efficacy population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CCI Vaccine | Number of Days of Usual Activity (i.e. Job, School,Household/Family/Community Activities) Lost Due to Influenza Disease, All Subjects | 0.06 Numebr of Days of Usual Activity Lost | Standard Deviation 0.635 |
| IVV Vaccine | Number of Days of Usual Activity (i.e. Job, School,Household/Family/Community Activities) Lost Due to Influenza Disease, All Subjects | 0.05 Numebr of Days of Usual Activity Lost | Standard Deviation 0.605 |
| Placebo | Number of Days of Usual Activity (i.e. Job, School,Household/Family/Community Activities) Lost Due to Influenza Disease, All Subjects | 0.16 Numebr of Days of Usual Activity Lost | Standard Deviation 1.006 |
Secondary
Number of Days of Usual Activity (i.e. Job, School,Household/Family/Community Activities) Lost, Subset of Subjects With Virus-Confirmed-Influenza
The analysis was done among the subset of subjects in the per protocol efficacy population who had culture-confirmed influenza.
Time frame: 6 Months
Population: Analysis was done on PP efficacy population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CCI Vaccine | Number of Days of Usual Activity (i.e. Job, School,Household/Family/Community Activities) Lost, Subset of Subjects With Virus-Confirmed-Influenza | 5.1 Numebr of Days of Usual Activity Lost | Standard Deviation 3.41 |
| IVV Vaccine | Number of Days of Usual Activity (i.e. Job, School,Household/Family/Community Activities) Lost, Subset of Subjects With Virus-Confirmed-Influenza | 4.0 Numebr of Days of Usual Activity Lost | Standard Deviation 3.4 |
| Placebo | Number of Days of Usual Activity (i.e. Job, School,Household/Family/Community Activities) Lost, Subset of Subjects With Virus-Confirmed-Influenza | 4.6 Numebr of Days of Usual Activity Lost | Standard Deviation 3.45 |
Secondary
Number Of Medical Visits (Inpatient and Outpatient) Due to Influenza Illness or Symptoms of Influenza, All Subjects
The number of subjects in this analysis included all subjects in the per protocol efficacy population.
Time frame: 6 Months
Population: Analysis was done of PP efficacy population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CCI Vaccine | Number Of Medical Visits (Inpatient and Outpatient) Due to Influenza Illness or Symptoms of Influenza, All Subjects | 0.01 Number of Medical Visits | Standard Deviation 0.138 |
| IVV Vaccine | Number Of Medical Visits (Inpatient and Outpatient) Due to Influenza Illness or Symptoms of Influenza, All Subjects | 0.01 Number of Medical Visits | Standard Deviation 0.134 |
| Placebo | Number Of Medical Visits (Inpatient and Outpatient) Due to Influenza Illness or Symptoms of Influenza, All Subjects | 0.03 Number of Medical Visits | Standard Deviation 0.262 |
Secondary
Number of Medical Visits (Inpatient and Outpatient), Subset of Subjects With Virus-Confirmed-Influenza
The analysis was done among the subset of subjects in the per protocol efficacy population who had culture-confirmed influenza.
Time frame: 6 Months
Population: Analysis was done of PP efficacy population.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CCI Vaccine | Number of Medical Visits (Inpatient and Outpatient), Subset of Subjects With Virus-Confirmed-Influenza | 0.8 Number of Medical Visits | Standard Deviation 0.92 |
| IVV Vaccine | Number of Medical Visits (Inpatient and Outpatient), Subset of Subjects With Virus-Confirmed-Influenza | 0.6 Number of Medical Visits | Standard Deviation 1 |
| Placebo | Number of Medical Visits (Inpatient and Outpatient), Subset of Subjects With Virus-Confirmed-Influenza | 0.8 Number of Medical Visits | Standard Deviation 1.16 |
Secondary
Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination
The solicited local and systemic reactogenicity were collected up to 7 days after vaccination for all three vaccine groups.
Time frame: Up to 7 days post vaccination
Population: Analysis was done on Safety population i.e. all subjects in the exposed population who provide post vaccination safety data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CCI Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Injection site Swelling | 218 Subjects |
| CCI Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Injection site Erythema | 510 Subjects |
| CCI Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Injection site Induration | 239 Subjects |
| CCI Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Injection site Ecchymosis | 143 Subjects |
| CCI Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Injection site Pain | 1158 Subjects |
| CCI Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Chills | 210 Subjects |
| CCI Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Malaise | 290 Subjects |
| CCI Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Myalgia | 450 Subjects |
| CCI Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Arthralgia | 108 Subjects |
| CCI Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Headache | 564 Subjects |
| CCI Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Sweating | 124 Subjects |
| CCI Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Fatigue | 390 Subjects |
| CCI Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Fever (>= 38 C) | 27 Subjects |
| CCI Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Oral Temp. (< 38 C) | 3786 Subjects |
| CCI Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Stayed home due to Reactions (N=3781, 3651, 3867) | 42 Subjects |
| CCI Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Analgesic medicines used | 394 Subjects |
| IVV Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Chills | 211 Subjects |
| IVV Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Malaise | 259 Subjects |
| IVV Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Headache | 551 Subjects |
| IVV Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Myalgia | 364 Subjects |
| IVV Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Oral Temp. (< 38 C) | 3648 Subjects |
| IVV Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Arthralgia | 111 Subjects |
| IVV Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Analgesic medicines used | 397 Subjects |
| IVV Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Sweating | 122 Subjects |
| IVV Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Injection site Pain | 893 Subjects |
| IVV Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Stayed home due to Reactions (N=3781, 3651, 3867) | 62 Subjects |
| IVV Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Injection site Erythema | 492 Subjects |
| IVV Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Fatigue | 404 Subjects |
| IVV Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Injection site Induration | 207 Subjects |
| IVV Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Injection site Ecchymosis | 110 Subjects |
| IVV Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Injection site Swelling | 181 Subjects |
| IVV Vaccine | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Fever (>= 38 C) | 21 Subjects |
| Placebo | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Sweating | 120 Subjects |
| Placebo | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Chills | 223 Subjects |
| Placebo | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Fever (>= 38 C) | 15 Subjects |
| Placebo | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Injection site Induration | 101 Subjects |
| Placebo | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Malaise | 237 Subjects |
| Placebo | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Analgesic medicines used | 386 Subjects |
| Placebo | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Injection site Pain | 375 Subjects |
| Placebo | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Fatigue | 384 Subjects |
| Placebo | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Myalgia | 275 Subjects |
| Placebo | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Injection site Swelling | 103 Subjects |
| Placebo | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Injection site Erythema | 391 Subjects |
| Placebo | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Arthralgia | 125 Subjects |
| Placebo | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Oral Temp. (< 38 C) | 3879 Subjects |
| Placebo | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Headache | 592 Subjects |
| Placebo | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Injection site Ecchymosis | 147 Subjects |
| Placebo | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | Stayed home due to Reactions (N=3781, 3651, 3867) | 42 Subjects |
Secondary
Number of Subjects With Culture-confirmed Influenza Illness Caused by Non-Vaccine Like Strains
The vaccine efficacy of CCI and IVV vaccines was estimated relative to placebo group as the number of subjects prevented against virus-confirmed symptomatic influenza A or B illness caused by non-vaccine-like strains.
Time frame: 6 Months
Population: Analysis was done on PP efficacy population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CCI Vaccine | Number of Subjects With Culture-confirmed Influenza Illness Caused by Non-Vaccine Like Strains | Overall | 30 Subjects |
| CCI Vaccine | Number of Subjects With Culture-confirmed Influenza Illness Caused by Non-Vaccine Like Strains | A/H3N2 | 0 Subjects |
| CCI Vaccine | Number of Subjects With Culture-confirmed Influenza Illness Caused by Non-Vaccine Like Strains | A/H1N1 | 1 Subjects |
| CCI Vaccine | Number of Subjects With Culture-confirmed Influenza Illness Caused by Non-Vaccine Like Strains | B | 29 Subjects |
| IVV Vaccine | Number of Subjects With Culture-confirmed Influenza Illness Caused by Non-Vaccine Like Strains | B | 27 Subjects |
| IVV Vaccine | Number of Subjects With Culture-confirmed Influenza Illness Caused by Non-Vaccine Like Strains | Overall | 29 Subjects |
| IVV Vaccine | Number of Subjects With Culture-confirmed Influenza Illness Caused by Non-Vaccine Like Strains | A/H1N1 | 0 Subjects |
| IVV Vaccine | Number of Subjects With Culture-confirmed Influenza Illness Caused by Non-Vaccine Like Strains | A/H3N2 | 2 Subjects |
| Placebo | Number of Subjects With Culture-confirmed Influenza Illness Caused by Non-Vaccine Like Strains | B | 59 Subjects |
| Placebo | Number of Subjects With Culture-confirmed Influenza Illness Caused by Non-Vaccine Like Strains | A/H3N2 | 8 Subjects |
| Placebo | Number of Subjects With Culture-confirmed Influenza Illness Caused by Non-Vaccine Like Strains | A/H1N1 | 8 Subjects |
| Placebo | Number of Subjects With Culture-confirmed Influenza Illness Caused by Non-Vaccine Like Strains | Overall | 74 Subjects |
Comparison: Vaccine efficacy (VE) of CCI vaccine vs. Placebo (Overall)~Simultaneous one-sided 97.5% confidence interval (CI) for the VE of CCI vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: 0.078Sidak-corrected score CI
Comparison: Vaccine efficacy (VE) of CCI vaccine vs. Placebo for A/H1N1 strain~Simultaneous one-sided 97.5% confidence interval (CI) for the VE of CCI vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: 0.104Sidak-corrected score CI
Comparison: Vaccine efficacy (VE) of CCI vaccine vs. Placebo for A/H3N2 strain~Simultaneous one-sided 97.5% confidence interval (CI) for the VE of CCI vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: 0.03Sidak-corrected score CI
Comparison: Vaccine efficacy (VE) of CCI vaccine vs. Placebo for B strain~Simultaneous one-sided 97.5% confidence interval (CI) for the VE of CCI vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: 0.376Sidak-corrected score CI
Comparison: Vaccine efficacy (VE) of IVV vaccine vs. Placebo (Overall)~Simultaneous one-sided 97.5% confidence interval (CI) for the VE of IVV vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: 0.085Sidak-corrected score CI
Comparison: Vaccine efficacy (VE) of IVV vaccine vs. Placebo for A/H1N1 strain~Simultaneous one-sided 97.5% confidence interval (CI) for the VE of IVV vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: 0.033Sidak-corrected score CI
Comparison: Vaccine efficacy (VE) of IVV vaccine vs. Placebo for A/H3N2 strain~Simultaneous one-sided 97.5% confidence interval (CI) for the VE of IVV vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: 0.265Sidak-corrected score CI
Comparison: Vaccine efficacy (VE) of IVV vaccine vs. Placebo for B strain~Simultaneous one-sided 97.5% confidence interval (CI) for the VE of IVV vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: 0.319Sidak-corrected score CI
Secondary
Number of Subjects With Influenza Caused by Vaccine-like and Non-vaccine-like Strains
The vaccine efficacy of CCI and IVV vaccines was estimated relative to placebo as the number of subjected prevented against virus-confirmed symptomatic influenza A or B illness caused by vaccine-like and non-vaccine-like strains.
Time frame: 6 Months
Population: Analysis was done on PP efficacy population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CCI Vaccine | Number of Subjects With Influenza Caused by Vaccine-like and Non-vaccine-like Strains | Overall | 42 Subjects |
| CCI Vaccine | Number of Subjects With Influenza Caused by Vaccine-like and Non-vaccine-like Strains | A/H3N2 | 6 Subjects |
| CCI Vaccine | Number of Subjects With Influenza Caused by Vaccine-like and Non-vaccine-like Strains | A/H1N1 | 6 Subjects |
| CCI Vaccine | Number of Subjects With Influenza Caused by Vaccine-like and Non-vaccine-like Strains | B | 30 Subjects |
| IVV Vaccine | Number of Subjects With Influenza Caused by Vaccine-like and Non-vaccine-like Strains | B | 27 Subjects |
| IVV Vaccine | Number of Subjects With Influenza Caused by Vaccine-like and Non-vaccine-like Strains | Overall | 49 Subjects |
| IVV Vaccine | Number of Subjects With Influenza Caused by Vaccine-like and Non-vaccine-like Strains | A/H1N1 | 10 Subjects |
| IVV Vaccine | Number of Subjects With Influenza Caused by Vaccine-like and Non-vaccine-like Strains | A/H3N2 | 12 Subjects |
| Placebo | Number of Subjects With Influenza Caused by Vaccine-like and Non-vaccine-like Strains | B | 61 Subjects |
| Placebo | Number of Subjects With Influenza Caused by Vaccine-like and Non-vaccine-like Strains | A/H3N2 | 25 Subjects |
| Placebo | Number of Subjects With Influenza Caused by Vaccine-like and Non-vaccine-like Strains | A/H1N1 | 57 Subjects |
| Placebo | Number of Subjects With Influenza Caused by Vaccine-like and Non-vaccine-like Strains | Overall | 140 Subjects |
Comparison: Vaccine efficacy (VE) of CCI vaccine vs. Placebo (Overall)~Simultaneous one-sided 97.5% confidence interval (CI) for the VE of CCI vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: <0.001Sidak-corrected score CI
Comparison: Vaccine efficacy (VE) of CCI vaccine vs. Placebo for A/H1N1 strain~Simultaneous one-sided 97.5% confidence interval (CI) for the VE of CCI vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: <0.001Sidak-corrected score CI
Comparison: Vaccine efficacy (VE) of CCI vaccine vs. Placebo for A/H3N2 strain~Simultaneous one-sided 97.5% confidence interval (CI) for the VE of CCI vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: 0.04Sidak-corrected score CI
Comparison: Vaccine efficacy (VE) of CCI vaccine vs. Placebo for B strain~Simultaneous one-sided 97.5% confidence interval (CI) for the VE of CCI vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: 0.37Sidak-corrected score CI
Comparison: Vaccine efficacy (VE) of IVV vaccine vs. Placebo (Overall)~Simultaneous one-sided 97.5% confidence interval (CI) for the VE of IVV vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: 0.003Sidak-corrected score CI
Comparison: Vaccine efficacy (VE) of IVV vaccine vs. Placebo for A/H1N1 strain~Simultaneous one-sided 97.5% confidence interval (CI) for the VE of IVV vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: <0.001Sidak-corrected score CI
Comparison: Vaccine efficacy (VE) of IVV vaccine vs. Placebo for A/H3N2 strain~Simultaneous one-sided 97.5% confidence interval (CI) for the VE of IVV vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: 0.53Sidak-corrected score CI
Comparison: Vaccine efficacy (VE) of IVV vaccine vs. Placebo for B strain~Simultaneous one-sided 97.5% confidence interval (CI) for the VE of IVV vaccine relative to Placebo was based on the Sidak-corrected score CIs for the two relative risks.p-value: 0.26Sidak-corrected score CI
Secondary
Percentages of Subjects Achieving Seroconversion After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo
As per the CBER guideline, seroconversion is defined as the percentage of subjects with a prevaccination HI titer \<10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, a ≥4-fold increase in postvaccination HI antibody titer. According to CBER criteria, the lower limit of the two-sided 95% CI for the percentage of subjects achieving seroconversion for HI antibody titer at day 22 met exceeded 40%.
Time frame: Three weeks after vaccination (day 22)
Population: Analysis was done on a subset of subjects who constituted the PP immunogenicity population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CCI Vaccine | Percentages of Subjects Achieving Seroconversion After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | A/H3N2 | 59 Percentages of subjects |
| CCI Vaccine | Percentages of Subjects Achieving Seroconversion After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | A/H1N1 | 78 Percentages of subjects |
| CCI Vaccine | Percentages of Subjects Achieving Seroconversion After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | B | 51 Percentages of subjects |
| IVV Vaccine | Percentages of Subjects Achieving Seroconversion After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | A/H3N2 | 68 Percentages of subjects |
| IVV Vaccine | Percentages of Subjects Achieving Seroconversion After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | A/H1N1 | 75 Percentages of subjects |
| IVV Vaccine | Percentages of Subjects Achieving Seroconversion After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | B | 68 Percentages of subjects |
| Placebo | Percentages of Subjects Achieving Seroconversion After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | A/H1N1 | 0 Percentages of subjects |
| Placebo | Percentages of Subjects Achieving Seroconversion After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | B | 0 Percentages of subjects |
| Placebo | Percentages of Subjects Achieving Seroconversion After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | A/H3N2 | 0 Percentages of subjects |
Secondary
Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo
Immunogenicity was measured as the percentage of subjects achieving HI titers ≥40 at baseline (day 1) and three weeks after (day 22) one vaccination of either cell-culture or egg-derived vaccine or placebo for each of the three influenza vaccine strains (A/H1N1, A/H3N2 and B), evaluated using hemagglutination inhibition (HI) egg-derived antigen assay. This criterion is met according to US (CBER) guideline if the lower limit of the two-sided 95% CI for the percentage of subjects achieving HI titers ≥40 is ≥70%.
Time frame: Before vaccination (day 1) and three weeks after vaccination (day 22)
Population: Analysis was done on a subset of subjects who constituted the PP immunogenicity population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| CCI Vaccine | Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | A/H1N1 - Day 1 | 48 Percentages of subjects |
| CCI Vaccine | Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | A/H1N1 - Day 22 | 99 Percentages of subjects |
| CCI Vaccine | Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | A/H3N2 - Day 1 | 63 Percentages of subjects |
| CCI Vaccine | Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | A/H3N2 - Day 22 | 99 Percentages of subjects |
| CCI Vaccine | Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | B - Day 1 | 25 Percentages of subjects |
| CCI Vaccine | Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | B - Day 22 | 78 Percentages of subjects |
| IVV Vaccine | Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | B - Day 22 | 92 Percentages of subjects |
| IVV Vaccine | Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | A/H1N1 - Day 1 | 53 Percentages of subjects |
| IVV Vaccine | Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | A/H3N2 - Day 22 | 99 Percentages of subjects |
| IVV Vaccine | Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | B - Day 1 | 23 Percentages of subjects |
| IVV Vaccine | Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | A/H1N1 - Day 22 | 98 Percentages of subjects |
| IVV Vaccine | Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | A/H3N2 - Day 1 | 58 Percentages of subjects |
| Placebo | Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | A/H1N1 - Day 22 | 60 Percentages of subjects |
| Placebo | Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | A/H3N2 - Day 1 | 71 Percentages of subjects |
| Placebo | Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | B - Day 22 | 22 Percentages of subjects |
| Placebo | Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | A/H3N2 - Day 22 | 65 Percentages of subjects |
| Placebo | Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | A/H1N1 - Day 1 | 60 Percentages of subjects |
| Placebo | Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | B - Day 1 | 22 Percentages of subjects |