Efficacy Study of Two Influenza Vaccines and Placebo in Healthy Adult Subjects
Sponsor
Novartis Vaccines (Industry)
Overall Status
Completed
CT.gov ID
NCT00630331
Collaborator
(none)
11,404
56
3
9
203.6
22.6
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
11404 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Participant)
Primary Purpose:
Prevention
Official Title:
A Phase III, Randomized, Observer-Blind, Placebo-Controlled, Multicenter Study to Assess Clinical Efficacy of a Cell-Derived Subunit Influenza Vaccine and an Egg-Derived Subunit Influenza Vaccine in the 2007-2008 Influenza Season in Healthy Adult Subjects
Study Start Date
:
Oct 1, 2007
Actual Primary Completion Date
:
Jul 1, 2008
Actual Study Completion Date
:
Jul 1, 2008
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: CCI Subjects received one dose of cell culture-derived influenza vaccine. |
Biological: Cell culture-derived influenza vaccine
One dose (0.5 mL) of cell culture-derived influenza vaccine, administered in the deltoid muscle.
|
| Experimental: IVV Subjects received one dose of the trivalent egg-derived influenza vaccine. |
Biological: Egg-derived influenza virus vaccine
One dose (0.5 mL) of the trivalent egg-derived influenza virus vaccine, administered in the deltoid muscle.
|
| Placebo Comparator: Placebo Subjects received one dose of phosphate buffered solution (PBS). |
Biological: Placebo
One dose (0.5 mL) of phosphate buffered solution.
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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 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 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.
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 49 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:
-
subjects 18 to 49 years of age;
-
in good health as determined by medical history and physical examination;
-
able and willing to provide written informed consent prior to any study procedure;
-
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:
-
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;
-
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;
-
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;
-
history of Guillain-Barré syndrome;
-
bleeding diathesis;
-
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;
-
receipt of another vaccine within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to Visit 1;
-
laboratory-confirmed influenza disease within 6 months prior to Visit 1;
-
receipt of an influenza vaccine within 6 months prior to Visit 1 or plans to receive influenza vaccine outside of this study;
-
experienced a temperature (≥100.0°F / ≥37.8°C) and/or any acute illness within 3 days prior to study vaccination;
-
pregnant or breast-feeding female;
-
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;
-
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;
-
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.;
-
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Site 14 | Denver | Colorado | United States | 80212 |
| 2 | Site 15 | Pembroke Pines | Florida | United States | 33024 |
| 3 | Site 17 | South Miami | Florida | United States | 33143 |
| 4 | Site 13 | Lenexa | Kansas | United States | 66219 |
| 5 | Site 2 | Bardstown | Kentucky | United States | 40004 |
| 6 | Site 1 | Saint Louis | Missouri | United States | 63140 |
| 7 | Site 4 | Edison | New Jersey | United States | 08817 |
| 8 | Site 10 | Binghamton | New York | United States | 13901 |
| 9 | Site 5 | Endwell | New York | United States | 13760 |
| 10 | Site 16 | Winston-Salem | North Carolina | United States | 27103 |
| 11 | Site 11 | Warwick | Rhode Island | United States | 02886 |
| 12 | Site 12 | Anderson | South Carolina | United States | 29621 |
| 13 | Site 9 | Austin | Texas | United States | 78705 |
| 14 | Site 8 | Dallas | Texas | United States | 75234 |
| 15 | Site 7 | Salt Lake City | Utah | United States | 84109 |
| 16 | Site 3 | Salt Lake City | Utah | United States | 84121 |
| 17 | Site 6 | Burke | Virginia | United States | 22105 |
| 18 | Site 25 | Espoo | Finland | 02100 | |
| 19 | Site 26 | Helsinki | Finland | 00100 | |
| 20 | Site 27 | Helsinki | Finland | 00930 | |
| 21 | Site 33 | Järvenpää | Finland | 04400 | |
| 22 | Site 35 | Kokkola | Finland | 67100 | |
| 23 | Site 34 | Kotka | Finland | 48600 | |
| 24 | Site 30 | Kuopio | Finland | 70100 | |
| 25 | Site 22 | Lahti | Finland | 15140 | |
| 26 | Site 31 | Oulu | Finland | 90100 | |
| 27 | Site 23 | Pori | Finland | 28120 | |
| 28 | Site 32 | Seinäjoki | Finland | 60100 | |
| 29 | Site 21 | Tampere | Finland | 33100 | |
| 30 | Site 24 | Turku | Finland | 20520 | |
| 31 | Site 28 | Vantaa | Finland | 01300 | |
| 32 | Site 29 | Vantaa | Finland | 01600 | |
| 33 | Site 49 | Bydgoszcz | Poland | 85-316 | |
| 34 | Site 53 | Gniewkowo | Poland | 88-140 | |
| 35 | Site 59 | Katowice | Poland | 40-084 | |
| 36 | Site 63 | Kielce | Poland | 25-711 | |
| 37 | Site 62 | Końskie | Poland | 26-200 | |
| 38 | Site 57 | Krakow | Poland | 30-510 | |
| 39 | Site 41 | Kraków | Poland | 30-969 | |
| 40 | Site 43 | Kraków | Poland | 31-115 | |
| 41 | Site 42 | Kraków | Poland | 31-503 | |
| 42 | Site 50 | Kraków | Poland | 31-832 | |
| 43 | Site 44 | Lubartów | Poland | 21 - 100 | |
| 44 | Site 45 | Lublin | Poland | 20-044 | |
| 45 | Site 65 | Oleśnica | Poland | 56-400 | |
| 46 | Site 47 | Olsztyn | Poland | 10-117 | |
| 47 | Site 48 | Olsztyn | Poland | 10-295 | |
| 48 | Site 46 | Olsztyn | Poland | 10-461 | |
| 49 | Site 58 | Radziszów | Poland | 32-052 | |
| 50 | Site 61 | Ruda Śląska | Poland | 41-703 | |
| 51 | Site 60 | Rzeszów | Poland | 35-324 | |
| 52 | Site 52 | Warszawa | Poland | 02-777 | |
| 53 | Site 55 | Wilkowice | Poland | 43-365 | |
| 54 | Site 64 | Wrocław | Poland | 51-312 | |
| 55 | Site 54 | Wąbrzeźno | Poland | 87-200 | |
| 56 | Site 51 | Łodź | Poland | 90-302 |
Sponsors and Collaborators
- Novartis Vaccines
Investigators
- Study Chair: Novartis Vaccines, Novartis Vaccines
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Novartis Vaccines
ClinicalTrials.gov Identifier:
NCT00630331
Other Study ID Numbers:
- V58P13
- 2007-002871-15
- 11580
First Posted:
Mar 7, 2008
Last Update Posted:
Aug 14, 2019
Last Verified:
Aug 1, 2019
Keywords provided by Novartis Vaccines
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants were enrolled at multiple centres in the US, Poland and Finland. |
|---|---|
| Pre-assignment Detail | All enrolled subjects were included in the trial. |
| Arm/Group Title | CCI Vaccine | IVV Vaccine | Placebo |
|---|---|---|---|
| Arm/Group Description | One dose of cell culture-derived influenza vaccine. | One dose of the trivalent egg-derived influenza virus vaccine. | One dose of phosphate buffered solution (PBS). |
| Period Title: Overall Study | |||
| STARTED | 3828 | 3676 | 3900 |
| COMPLETED | 3622 | 3510 | 3712 |
| NOT COMPLETED | 206 | 166 | 188 |
Baseline Characteristics
| Arm/Group Title | CCI Vaccine | IVV Vaccine | Placebo | Total |
|---|---|---|---|---|
| Arm/Group Description | One dose of cell culture-derived influenza vaccine. | One dose of the trivalent egg-derived influenza virus vaccine. | One dose of phosphate buffered solution (PBS). | Total of all reporting groups |
| Overall Participants | 3828 | 3676 | 3900 | 11404 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
32.7
(10.1)
|
33.0
(10.2)
|
32.7
(10.2)
|
32.8
(10.2)
|
| Sex/Gender, Customized (Subjects) [Number] | ||||
| Female |
2088
|
2026
|
2176
|
6290
|
| Male |
1740
|
1649
|
1722
|
5111
|
| Not Available |
0
|
1
|
2
|
3
|
Outcome Measures
| Title | Number of Subjects With Culture-Confirmed Influenza Illness Caused by Vaccine-like Strains |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | CCI Vaccine | IVV Vaccine | Placebo |
|---|---|---|---|
| Arm/Group Description | One dose of cell culture-derived influenza vaccine. | One dose of the trivalent egg-derived influenza virus vaccine. | One dose of phosphate buffered solution (PBS). |
| Measure Participants | 3776 | 3638 | 3843 |
| Overall |
7
|
9
|
44
|
| A/Wisconsin/67/2005 (H3N2)-like |
2
|
1
|
0
|
| A/Solomon Islands/3/2006 (H1N1)-like |
5
|
8
|
43
|
| B/Malaysia/2506/2004-like |
0
|
0
|
1
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | CCI Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of CCI vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 83.8 | |
| Confidence Interval |
(1-Sided) 97.5% 61.0 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | CCI Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of CCI vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 88.2 | |
| Confidence Interval |
(1-Sided) 97.5% 67.4 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | CCI Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.999 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of CCI vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | For strain A/H3N2, the vaccine efficacy of the CCI vaccine vs. placebo was not evaluable since no influenza case was observed in the placebo group. | |
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | CCI Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.394 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of CCI vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 100 | |
| Confidence Interval |
(1-Sided) 97.5% - 410 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | IVV Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.004 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of IVV vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 78.4 | |
| Confidence Interval |
(1-Sided) 97.5% 52.1 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | IVV Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.002 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of IVV vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 80.3 | |
| Confidence Interval |
(1-Sided) 97.5% 54.7 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | IVV Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.992 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of IVV vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | For strain A/H3N2, the vaccine efficacy of the IVV vaccine vs. placebo was not evaluable since no influenza case was observed in the placebo group. | |
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | IVV Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.400 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of IVV vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 100 | |
| Confidence Interval |
(1-Sided) 97.5% - 429.4 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Subjects With Culture-confirmed Influenza Illness Caused by Non-Vaccine Like Strains |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on PP efficacy population. |
| Arm/Group Title | CCI Vaccine | IVV Vaccine | Placebo |
|---|---|---|---|
| Arm/Group Description | One dose of cell culture-derived influenza vaccine. | One dose of the trivalent egg-derived influenza virus vaccine. | One dose of phosphate buffered solution (PBS). |
| Measure Participants | 3776 | 3638 | 3843 |
| Overall |
30
|
29
|
74
|
| A/H3N2 |
0
|
2
|
8
|
| A/H1N1 |
1
|
0
|
8
|
| B |
29
|
27
|
59
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | CCI Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.078 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of CCI vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 58.7 | |
| Confidence Interval |
(1-Sided) 97.5% 33.5 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | CCI Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.104 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of CCI vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 87.3 | |
| Confidence Interval |
(1-Sided) 97.5% 4.6 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | CCI Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.030 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of CCI vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 100 | |
| Confidence Interval |
(1-Sided) 97.5% 36.3 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | CCI Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.376 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of CCI vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 50.0 | |
| Confidence Interval |
(1-Sided) 97.5% 17.5 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | IVV Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.085 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of IVV vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 58.6 | |
| Confidence Interval |
(1-Sided) 97.5% 32.9 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | IVV Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.033 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of IVV vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 100 | |
| Confidence Interval |
(1-Sided) 97.5% 33.9 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | IVV Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.265 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of IVV vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 73.6 | |
| Confidence Interval |
(1-Sided) 97.5% -30.0 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | IVV Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.319 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of IVV vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 51.7 | |
| Confidence Interval |
(1-Sided) 97.5% 19.4 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Number of Subjects With Influenza Caused by Vaccine-like and Non-vaccine-like Strains |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on PP efficacy population. |
| Arm/Group Title | CCI Vaccine | IVV Vaccine | Placebo |
|---|---|---|---|
| Arm/Group Description | One dose of cell culture-derived influenza vaccine. | One dose of the trivalent egg-derived influenza virus vaccine. | One dose of phosphate buffered solution (PBS). |
| Measure Participants | 3776 | 3638 | 3843 |
| Overall |
42
|
49
|
140
|
| A/H3N2 |
6
|
12
|
25
|
| A/H1N1 |
6
|
10
|
57
|
| B |
30
|
27
|
61
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | CCI Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of CCI vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 69.5 | |
| Confidence Interval |
(1-Sided) 97.5% 55.0 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | CCI Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of CCI vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 89.3 | |
| Confidence Interval |
(1-Sided) 97.5% 73.0 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | CCI Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.040 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of CCI vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 75.6 | |
| Confidence Interval |
(1-Sided) 97.5% 35.1 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | CCI Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.37 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of CCI vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 49.9 | |
| Confidence Interval |
(1-Sided) 97.5% 18.2 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 5
| Statistical Analysis Overview | Comparison Group Selection | IVV Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.003 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of IVV vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 63.0 | |
| Confidence Interval |
(1-Sided) 97.5% 46.7 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 6
| Statistical Analysis Overview | Comparison Group Selection | IVV Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of IVV vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 81.5 | |
| Confidence Interval |
(1-Sided) 97.5% 60.9 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 7
| Statistical Analysis Overview | Comparison Group Selection | IVV Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.53 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of IVV vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 49.3 | |
| Confidence Interval |
(1-Sided) 97.5% - 9.0 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 8
| Statistical Analysis Overview | Comparison Group Selection | IVV Vaccine, Placebo |
|---|---|---|
| Comments | 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. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.26 |
| Comments | Adjusted p-values are from score statistic with Sidak correction testing the null hypothesis that the VE of IVV vs. placebo is <= 40% (the relative risk, >= 0.60). If adjusted p-value is <0.025, then the comparison is statistically significant. | |
| Method | Sidak-corrected score CI | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Vaccine Efficacy |
| Estimated Value | 53.2 | |
| Confidence Interval |
(1-Sided) 97.5% 22.2 to |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Influenza-Associated Days in Bed, All Subjects |
|---|---|
| Description | The number of subjects in this analysis included all subjects in the per protocol efficacy population. |
| Time Frame | 6 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on the PP efficacy population. |
| Arm/Group Title | CCI Vaccine | IVV Vaccine | Placebo |
|---|---|---|---|
| Arm/Group Description | One dose of cell culture-derived influenza vaccine. | One dose of the trivalent egg-derived influenza virus vaccine. | One dose of phosphate buffered solution (PBS). |
| Measure Participants | 3775 | 3638 | 3837 |
| Mean (Standard Deviation) [Number of Days] |
0.04
(0.496)
|
0.04
(0.404)
|
0.12
(0.777)
|
| Title | Influenza-Associated Days in Bed, Subset of Subjects With Virus-Confirmed- Influenza |
|---|---|
| Description | The analysis was done among the subset of subjects in the per protocol efficacy population who had culture-confirmed influenza. |
| Time Frame | 6 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on PP efficacy population. |
| Arm/Group Title | CCI Vaccine | IVV Vaccine | Placebo |
|---|---|---|---|
| Arm/Group Description | One dose of cell culture-derived influenza vaccine. | One dose of the trivalent egg-derived influenza virus vaccine. | One dose of phosphate buffered solution (PBS). |
| Measure Participants | 180 | 230 | 332 |
| Mean (Standard Deviation) [Number of Days] |
3.9
(2.62)
|
2.9
(1.98)
|
3.4
(2.4)
|
| Title | Number Of Medical Visits (Inpatient and Outpatient) Due to Influenza Illness or Symptoms of Influenza, All Subjects |
|---|---|
| Description | The number of subjects in this analysis included all subjects in the per protocol efficacy population. |
| Time Frame | 6 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done of PP efficacy population. |
| Arm/Group Title | CCI Vaccine | IVV Vaccine | Placebo |
|---|---|---|---|
| Arm/Group Description | One dose of cell culture-derived influenza vaccine. | One dose of the trivalent egg-derived influenza virus vaccine. | One dose of phosphate buffered solution (PBS). |
| Measure Participants | 3775 | 3638 | 3838 |
| Mean (Standard Deviation) [Number of Medical Visits] |
0.01
(0.138)
|
0.01
(0.134)
|
0.03
(0.262)
|
| Title | Number of Medical Visits (Inpatient and Outpatient), Subset of Subjects With Virus-Confirmed-Influenza |
|---|---|
| Description | The analysis was done among the subset of subjects in the per protocol efficacy population who had culture-confirmed influenza. |
| Time Frame | 6 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done of PP efficacy population. |
| Arm/Group Title | CCI Vaccine | IVV Vaccine | Placebo |
|---|---|---|---|
| Arm/Group Description | One dose of cell culture-derived influenza vaccine. | One dose of the trivalent egg-derived influenza virus vaccine. | One dose of phosphate buffered solution (PBS). |
| Measure Participants | 180 | 230 | 332 |
| Mean (Standard Deviation) [Number of Medical Visits] |
0.8
(0.92)
|
0.6
(1.0)
|
0.8
(1.16)
|
| Title | Number of Days of Usual Activity (i.e. Job, School,Household/Family/Community Activities) Lost Due to Influenza Disease, All Subjects |
|---|---|
| Description | The number of subjects in this analysis included all subjects in the per protocol efficacy population. |
| Time Frame | 6 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on PP efficacy population. |
| Arm/Group Title | CCI Vaccine | IVV Vaccine | Placebo |
|---|---|---|---|
| Arm/Group Description | One dose of cell culture-derived influenza vaccine. | One dose of the trivalent egg-derived influenza virus vaccine. | One dose of phosphate buffered solution (PBS). |
| Measure Participants | 3775 | 3638 | 3837 |
| Mean (Standard Deviation) [Numebr of Days of Usual Activity Lost] |
0.06
(0.635)
|
0.05
(0.605)
|
0.16
(1.006)
|
| Title | Number of Days of Usual Activity (i.e. Job, School,Household/Family/Community Activities) Lost, Subset of Subjects With Virus-Confirmed-Influenza |
|---|---|
| Description | The analysis was done among the subset of subjects in the per protocol efficacy population who had culture-confirmed influenza. |
| Time Frame | 6 Months |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on PP efficacy population. |
| Arm/Group Title | CCI Vaccine | IVV Vaccine | Placebo |
|---|---|---|---|
| Arm/Group Description | One dose of cell culture-derived influenza vaccine. | One dose of the trivalent egg-derived influenza virus vaccine. | One dose of phosphate buffered solution (PBS). |
| Measure Participants | 180 | 230 | 332 |
| Mean (Standard Deviation) [Numebr of Days of Usual Activity Lost] |
5.1
(3.41)
|
4.0
(3.4)
|
4.6
(3.45)
|
| Title | Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on a subset of subjects who constituted the PP immunogenicity population. |
| Arm/Group Title | CCI Vaccine | IVV Vaccine | Placebo |
|---|---|---|---|
| Arm/Group Description | One dose of cell culture-derived influenza vaccine. | One dose of the trivalent egg-derived influenza virus vaccine. | One dose of phosphate buffered solution (PBS). |
| Measure Participants | 228 | 695 | 55 |
| A/H1N1 - Day 1 |
48
|
53
|
60
|
| A/H1N1 - Day 22 |
99
|
98
|
60
|
| A/H3N2 - Day 1 |
63
|
58
|
71
|
| A/H3N2 - Day 22 |
99
|
99
|
65
|
| B - Day 1 |
25
|
23
|
22
|
| B - Day 22 |
78
|
92
|
22
|
| Title | Percentages of Subjects Achieving Seroconversion After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo |
|---|---|
| Description | 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on a subset of subjects who constituted the PP immunogenicity population. |
| Arm/Group Title | CCI Vaccine | IVV Vaccine | Placebo |
|---|---|---|---|
| Arm/Group Description | One dose of cell culture-derived influenza vaccine. | One dose of the trivalent egg-derived influenza virus vaccine. | One dose of phosphate buffered solution (PBS). |
| Measure Participants | 228 | 695 | 55 |
| A/H1N1 |
78
|
75
|
0
|
| A/H3N2 |
59
|
68
|
0
|
| B |
51
|
68
|
0
|
| Title | Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Analysis was done on Safety population i.e. all subjects in the exposed population who provide post vaccination safety data. |
| Arm/Group Title | CCI Vaccine | IVV Vaccine | Placebo |
|---|---|---|---|
| Arm/Group Description | One dose of cell culture-derived influenza vaccine. | One dose of the trivalent egg-derived influenza virus vaccine. | One dose of phosphate buffered solution (PBS). |
| Measure Participants | 3813 | 3669 | 3894 |
| Injection site Pain |
1158
|
893
|
375
|
| Injection site Erythema |
510
|
492
|
391
|
| Injection site Induration |
239
|
207
|
101
|
| Injection site Ecchymosis |
143
|
110
|
147
|
| Injection site Swelling |
218
|
181
|
103
|
| Chills |
210
|
211
|
223
|
| Malaise |
290
|
259
|
237
|
| Myalgia |
450
|
364
|
275
|
| Arthralgia |
108
|
111
|
125
|
| Headache |
564
|
551
|
592
|
| Sweating |
124
|
122
|
120
|
| Fatigue |
390
|
404
|
384
|
| Fever (>= 38 C) |
27
|
21
|
15
|
| Oral Temp. (< 38 C) |
3786
|
3648
|
3879
|
| Stayed home due to Reactions (N=3781, 3651, 3867) |
42
|
62
|
42
|
| Analgesic medicines used |
394
|
397
|
386
|
Adverse Events
| Time Frame | Serious Adverse Events were collected throughout the study period (i.e., 6 months). | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The analysis was done on the safety population. | |||||
| Arm/Group Title | CCI Vaccine | IVV Vaccine | Placebo | |||
| Arm/Group Description | One dose of cell culture-derived influenza vaccine. | One dose of the trivalent egg-derived influenza virus vaccine. | One dose of phosphate buffered solution (PBS). | |||
All Cause Mortality |
||||||
| CCI Vaccine | IVV Vaccine | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| CCI Vaccine | IVV Vaccine | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 42/3813 (1.1%) | 35/3669 (1%) | 38/3894 (1%) | |||
| Cardiac disorders | ||||||
| Cardiac Failure Congestive | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Coronary Artery disease | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Ear and labyrinth disorders | ||||||
| Vertigo Positional | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Endocrine disorders | ||||||
| Hyperthyroidism | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Eye disorders | ||||||
| Mydriasis | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Gastrointestinal disorders | ||||||
| Abdominal Pain | 1/3813 (0%) | 1 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Abdominal Pain Upper | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 1/3894 (0%) | 1 |
| Anal Fistula | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Colitis Ischaemic | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Crohn's Disease | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Gastrooesophageal Reflux Disease | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Haemorrhoids | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Inguinal Hernia | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 1/3894 (0%) | 1 |
| Intestinal Obstructon | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Pancreatitis Acute | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Peritoneal Cyst | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Salivary Duct Inflammation | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Salivary Gland Calculus | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Small Intestinal Obstruction | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Vomiting in Pregnancy | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| General disorders | ||||||
| Chest Pain | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Death | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Non-Cardiac Chest Pain | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Hepatobiliary disorders | ||||||
| Cholangitis Sclerosing | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Cholecystitis | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Cholecystitis Acute | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Cholelithiasis | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Hepatitis Acute | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Jaundice | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Infections and infestations | ||||||
| Acute Sinusitis | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Acute Tonsillitis | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Appendicitis | 1/3813 (0%) | 1 | 1/3669 (0%) | 1 | 3/3894 (0.1%) | 3 |
| Breast Cellulitis | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Cellulitis | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Diverticulitis | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Gastroenteritis Viral | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Infection | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Lung Abscess | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Mastitis Bacterial | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Perirectal Abscess | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Peritonsillar Abscess | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Pharyngitis | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 2/3894 (0.1%) | 2 |
| Pneumonia | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 2/3894 (0.1%) | 2 |
| Pyelonephritis Acute | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Urinary Tract Infection | 1/3813 (0%) | 1 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Wound Infection | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||
| Abdominal Injury | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Alcohol Poisoning | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Ankle Fracture | 2/3813 (0.1%) | 2 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Chest Injury | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Extradural Haematoma | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Foot Fracture | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Joint Injury | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Road Traffic Accident | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Skull Fracture | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Subdural Haematoma | 1/3813 (0%) | 1 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Tendon Rupture | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Upper Limb Fracture | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Wound | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Metabolism and nutrition disorders | ||||||
| Obesity | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Musculoskeletal and connective tissue disorders | ||||||
| Back Pain | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 2/3894 (0.1%) | 2 |
| Intervertebral Disc Protrusion | 2/3813 (0.1%) | 2 | 0/3669 (0%) | 0 | 2/3894 (0.1%) | 2 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Adenocarcinoma of the Cervix | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Bone Neoplasm | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Breast Cancer | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Carcinoid Tumour | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Leiomyosarcoma | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Ovarian Cancer | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Nervous system disorders | ||||||
| Cerebral Haemorrhage | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Epilepsy | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Headache | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Loss of Consciousness | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Migraine | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Syncope | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Tethered Cord Syndrome | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Pregnancy, puerperium and perinatal conditions | ||||||
| Abortion Spontaneous | 1/3813 (0%) | 1 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Delivery | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Ectopic Pregnancy | 1/3813 (0%) | 1 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Psychiatric disorders | ||||||
| Acute Stress Disorder | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Anxiety | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Bipolar Disorder | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Borderline Personality Disorder | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Major Depression | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Psychotic Disorder | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Renal and urinary disorders | ||||||
| Bladder Prolapse | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Dysuria | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Renal Failure Acute | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Reproductive system and breast disorders | ||||||
| Breast Hyperplasia | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Dysmenorrhoea | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Haemorrhagic Ovarian Cyst | 0/3813 (0%) | 0 | 2/3669 (0.1%) | 2 | 0/3894 (0%) | 0 |
| Menometrorrhagia | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Pelvic Pain | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Polycystic Ovaries | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Uterine Haemorrhage | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||||
| Dyspnoea | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Nasal Septum Deviation | 1/3813 (0%) | 1 | 2/3669 (0.1%) | 2 | 0/3894 (0%) | 0 |
| Pulmonary Embolism | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Tonsillar Hypertrophy | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||
| Dermatitis Atopic | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Social circumstances | ||||||
| Homicide | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Surgical and medical procedures | ||||||
| Aortic Valve Replacement | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Appendicetomy | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
| Knee Operation | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Medical Device Removal | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Nasal Septal Operation | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Rhinoplasty | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Tendon Operation | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Vascular disorders | ||||||
| Deep Vein Thrombosis | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Hypertension | 1/3813 (0%) | 1 | 0/3669 (0%) | 0 | 0/3894 (0%) | 0 |
| Thrombophlebitis | 0/3813 (0%) | 0 | 1/3669 (0%) | 1 | 0/3894 (0%) | 0 |
| Varicose Vein | 0/3813 (0%) | 0 | 0/3669 (0%) | 0 | 1/3894 (0%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
| CCI Vaccine | IVV Vaccine | Placebo | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1949/3813 (51.1%) | 1703/3669 (46.4%) | 1387/3894 (35.6%) | |||
| General disorders | ||||||
| Chills | 212/3813 (5.6%) | 212/3669 (5.8%) | 225/3894 (5.8%) | |||
| Fatigue | 390/3813 (10.2%) | 404/3669 (11%) | 386/3894 (9.9%) | |||
| Injection Site Erythema | 510/3813 (13.4%) | 492/3669 (13.4%) | 391/3894 (10%) | |||
| Injection Site Induration | 239/3813 (6.3%) | 207/3669 (5.6%) | 101/3894 (2.6%) | |||
| Injection Site Pain | 1158/3813 (30.4%) | 893/3669 (24.3%) | 375/3894 (9.6%) | |||
| Injection Site Swelling | 218/3813 (5.7%) | 181/3669 (4.9%) | 103/3894 (2.6%) | |||
| Malaise | 290/3813 (7.6%) | 260/3669 (7.1%) | 238/3894 (6.1%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Myalgia | 451/3813 (11.8%) | 369/3669 (10.1%) | 278/3894 (7.1%) | |||
| Nervous system disorders | ||||||
| Headache | 571/3813 (15%) | 554/3669 (15.1%) | 597/3894 (15.3%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Posting Director |
|---|---|
| Organization | Novartis Vaccines and Diagnostics |
| Phone | |
| RegistryContactVaccinesUS@novartis.com |
Responsible Party:
Novartis Vaccines
ClinicalTrials.gov Identifier:
NCT00630331
Other Study ID Numbers:
- V58P13
- 2007-002871-15
- 11580
First Posted:
Mar 7, 2008
Last Update Posted:
Aug 14, 2019
Last Verified:
Aug 1, 2019