Immunogenicity, Safety, Reactogenicity, Efficacy, Effectiveness and Lot Consistency of FluBlok
Study Details
Study Description
Brief Summary
The purpose of this study was to evaluate a single dose of FluBlok in terms of safety, efficacy and effectiveness in prevention of influenza and influenza-like illness and assess clinical lot-to-lot consistency in manufacturing by evaluating and comparing the immunogenicity of three different lots of FluBlok in a subset of participants.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
Detailed Description
All currently licensed influenza vaccines in the United States were produced in embryonated hen's eggs. There were several well-recognized disadvantages to the use of eggs as the substrate for influenza vaccine. Eggs required specialized manufacturing facilities and could be difficult to scale up rapidly in response to an emerging need such as a pandemic. It was usually necessary to adapt candidate vaccine viruses for high-yield growth in eggs, a process that could be time consuming, was not always successful, and could select receptor variants that might have suboptimal immunogenicity. In addition, agricultural diseases that affected chicken flocks, and that might be an important issue in a pandemic due to an avian influenza virus strain, could easily disrupt the supply of eggs for vaccine manufacturing. Therefore, development of alternative substrates for influenza vaccine production had been identified as a high-priority objective.
One potential alternative method for production of influenza vaccine was expression of the influenza virus hemagglutinin (HA) using recombinant deoxyribonucleic acid (DNA) techniques. This alternative avoided dependence on eggs and was very efficient because of the high levels of protein expression under the control of the baculovirus polyhedrin promoter.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: FluBlok (Lots A, B, C) Participants received a single 0.5 milliliters (mL) dose of FluBlok vaccine from any of the Lots A, B, or C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. |
Biological: FluBlok®
Dose: 0.5 mL, single dose; Route of administration: intramuscular. Recombinant Trivalent Hemagglutinin Influenza Vaccine containing 45 microgram (mcg) of each hemagglutinin derived from A/Solomon Islands/3/2006 (H1N1), A/Wisconsin/67/2005 (H3N2), and B/Malaysia/2506/2004
Other Names:
|
Placebo Comparator: Placebo Participants received a single dose of placebo matched to FluBlok, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. |
Biological: Placebo
Dose: 0.5 mL normal saline for injection, single dose; Route of administration: intramuscular
|
Outcome Measures
Primary Outcome Measures
- Number of Participants Reporting Solicited Injection Site (Local) Reactions [Within 7 days post vaccination]
Solicited reaction (reactogenicity event) was an adverse event (AE) that was pre-listed in electronic case report form(eCRF), considered to be related to vaccination and recorded by participant by means of memory aid. Injection sites reaction included pain,bruising,redness,swelling. Pain and bruising:Grade0: didn't have it at all; Grade1: noticed it, but it didn't interfere with usual activities at all; Grade2: had it, and it was bad enough to prevent a significant part of usual activities; Grade3: had it, and it prevented most or all of normal activities, or had to see a doctor for prescription medicine, Redness and swelling: participants measured largest diameter of any injection site reaction and grade them from 0 to 3, where Grade0: measured less than(<)10 milliliters(mm); Grade1: larger than or equal to(>=) 10mm and <20mm; Grade 2: >=20mm and <50mm; Grade3: >=50mm. Participants with multiple symptoms in same category were counted once per category using symptom with maximum grade
- Number of Participants Reporting Solicited Systemic Reactions [Within 7 days post vaccination]
Solicited reaction (reactogenicity event) was an AE that was pre-listed in eCRF, considered to be related to vaccination recorded by the participant by means of a memory aid between the day of vaccination (Day 0) and Day 7 post vaccination. Systemic events included fever, fatigue, shivering, joint pain, muscle pain, headache, and nausea. Fever: >=100.4 degree Fahrenheit (ºF) to <101.1ºF; >=101.2ºF to <102.2ºF; >=102.2ºF; Fatigue, shivering, joint pain, muscle pain, headache and nausea: Grade 0: didn't have it at all; Grade 1: noticed it, but it didn't interfere with usual activities at all; Grade 2: had it, and it was bad enough to prevent a significant part of usual activities; and Grade 3: had it, and it prevented most or all of normal activities, or had to see a doctor for prescription medicine. Participants with multiple symptoms in the same category were counted once per category using the symptom with the maximum grade.
- Number of Participants Reporting Unsolicited Adverse Events [From Day 0 (post-vaccination) through Day 28 post vaccination]
An AE was defined as any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a study vaccine, whether or not considered to be related to the study vaccine. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination, ascertained during follow-up visit or telephone contact up to (and including) the Day 28 contact, whether reported spontaneously by the participant or in response to general questions about current or interim health status.
- Lot Consistency: Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies Following FluBlok Vaccination [Day 28 post vaccination]
GMTs of anti-influenza antibodies were measured using a single radial immunodiffusion (SRID) assay for 3 strains: A/Solomon Islands [H1N1], A/Wisconsin [H3N2], and B/Malaysia. Titers were expressed in terms of 1/dilution.
- Percentage of Participants With Positive Cell Culture/Culture-Confirmed Influenza Like Illness as Defined by Centers for Disease Control and Prevention (CDC-ILI) [14 days post vaccination through and up to 6 months]
CDC-defined ILI was defined as fever (body temperature >=100ºF oral accompanied by cough and/or sore throat, on the same day or on consecutive days) due to strains represented in the vaccine.
Secondary Outcome Measures
- Percentage of Participants With Seroprotection to Influenza Vaccine Antigens After Vaccination With FluBlok [28 days post vaccination]
Anti-influenza antibodies were measured using an HAI assay for 3 strains: A/Solomon Islands [H1N1], A/Wisconsin [H3N2] and B/Malaysia. Seroprotection was defined as a post-vaccination HAI antibody titer of >=1:40.
- Percentage of Participants With Seroconversion to Influenza Vaccine Antigens After Vaccination With FluBlok [28 days post vaccination]
Anti-influenza antibodies were measured using an HAI assay for 3 strains: A/Solomon Islands [H1N1], A/Wisconsin [H3N2] and B/Malaysia. Seroconversion was defined as a post-vaccination titer of >=1:40 in participants with undetectable baseline antibody (HI titer = <1:10) or a >=4-fold rise in antibody in participants with a baseline titer of >=1:10, with the achievement of post-vaccination titer of at least 1:40.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Healthy adult aged 18-49 years.
-
Provided informed consent prior to any study procedures.
-
Able to comply with all study procedures.
-
Available for follow-up for the duration of the influenza season.
-
Women of child-bearing potential must have had a negative urine pregnancy test at the time of randomization and must be willing to use an adequate form of contraception (includes abstinence, condom with spermicide, licensed hormonal contraceptive, intrauterine device [IUD], monogamous relationship with a vasectomized partner) during the course of the study.
Exclusion Criteria:
-
Long-term use of oral steroids, parenteral steroids, or high-dose inhaled steroids (greater than [>] 800 mcg/day of beclomethasone dipropionate or equivalent) within the preceding 6 months (Nasal and topical steroids were allowed).
-
Presence of high-risk conditions or other characteristics were considered to be indication for influenza vaccination, as defined by the Advisory Committee on Immunization Practices.
-
Acute febrile illness (defined as having a temperature greater than or equal to [>=]100 degrees Fahrenheit) or upper respiratory tract illness within 72 hours of vaccination. Participants with acute febrile illness were rescheduled after fever resolved.
-
Use of experimental vaccines or any influenza vaccine other than FluBlOk after May 31st 2007 for the 2008 Southern Hemisphere or 2007 to 2008 Northern hemisphere epidemic seasons.
-
Immunosuppression as a result of an underlying illness or treatment, or used anticancer chemotherapy or radiation therapy within the preceding 36 months.
-
Any malignancy diagnosed or treated actively during the past five (5) years, with two (2) exceptions. Participant with any history of lymphoproliferative disorder were excluded. However, participants with a history of localized non-melanotic skin cancer were eligible.
-
Receipt of any other licensed vaccines within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrollment in this study.
-
Receipt of an experimental agent (vaccine, drug, biologic, device, blood product or medication) within 1 month prior to enrollment in this study, or expected to receive an experimental agent during study period.
-
Receipt of parenteral immunoglobulin or other blood product within the three months prior to study vaccination.
-
Major psychiatric diagnosis including schizophrenia, bipolar disease or other major depression, or any diagnosis of dementia or associated concomitant medications (e.g., Aricept) used for treating dementia.
-
Known active human immunodeficiency virus, hepatitis B, or hepatitis C infection.
-
History of alcohol or drug abuse in the last 5 years.
-
Not available for three or more consecutive weeks during flu surveillance period.
-
Any acute or chronic condition that, in the opinion of the investigator, would render vaccination unsafe or interfere with the evaluation of responses or render the participant unable to meet the requirements of the protocol.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Impact Clinical Trials | Beverly Hills | California | United States | 90211 |
2 | Benchmark Research - Sacramento | Sacramento | California | United States | 95816 |
3 | Benchmark Research - San Francisco | San Francisco | California | United States | 94102 |
4 | University Clinical Research, Inc | Pembroke Pines | Florida | United States | 33024 |
5 | Vince and Associates | Overland Park | Kansas | United States | 66212 |
6 | Kentucky pediatric /Adult Research | Bardstown | Kentucky | United States | 40004 |
7 | Benchmarch Research - New Orleans | Metairie | Louisiana | United States | 70006 |
8 | University of Maryland - Baltimore | Baltimore | Maryland | United States | 21201 |
9 | Saint Louis University | Saint Louis | Missouri | United States | 63110 |
10 | Meridian Clinical Research | Omaha | Nebraska | United States | 68134 |
11 | Regional Clinical Research, Inc. | Endwell | New York | United States | 13760 |
12 | Rochester Medical Center | Rochester | New York | United States | 14642 |
13 | Carolina Medical Trials | Winston-Salem | North Carolina | United States | 27103 |
14 | Sterling Research | Cincinnati | Ohio | United States | 45246 |
15 | Primary Physicians Research - Pediatric Alliance St. Clair | Pittsburgh | Pennsylvania | United States | 15241 |
16 | Primary Physicians Research | Pittsburgh | Pennsylvania | United States | 15241 |
17 | Vanderbilt University Medical Center | Nashville | Tennessee | United States | 37232 |
18 | Benchmarch Research - Austin | Austin | Texas | United States | 78705 |
19 | Benchmark Research - Fort Worth | Fort Worth | Texas | United States | 76135 |
20 | Baylor College of Medicine | Houston | Texas | United States | 77030 |
21 | Benchmark Research - San Angelo | San Angelo | Texas | United States | 76904 |
22 | Jean Brown Research | Salt Lake City | Utah | United States | 84124 |
23 | University of Virginia Health System | Charlottesville | Virginia | United States | 22908 |
24 | Marshfield Clinic | Marshfield | Wisconsin | United States | 54449 |
Sponsors and Collaborators
- Sanofi
- Protein Sciences Corporation
Investigators
- Principal Investigator: John J Treanor, MD, University of Rochester
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- PSC04
Study Results
Participant Flow
Recruitment Details | The study was conducted at 24 active centers in the United States from 15-September-2007 to 28-May-2008. |
---|---|
Pre-assignment Detail | A total of 4648 participants were randomized in the study. Participants were randomized in 1:1 ratio to receive FluBlok or Placebo. The FluBlok assignment was further stratified into three lots, A, B and C to assess lot consistency. |
Arm/Group Title | FluBlok (Lots A, B, C) | Placebo |
---|---|---|
Arm/Group Description | Participants received a single 0.5 milliliters (mL) dose of FluBlok vaccine from any of the Lots A, B, or C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. | Participants received a single dose of placebo matched to FluBlok, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. |
Period Title: Overall Study | ||
STARTED | 2344 | 2304 |
COMPLETED | 2049 | 2022 |
NOT COMPLETED | 295 | 282 |
Baseline Characteristics
Arm/Group Title | FluBlok (Lots A, B, C) | Placebo | Total |
---|---|---|---|
Arm/Group Description | Participants received a single 0.5 mL dose of FluBlok vaccine from any of the Lots A, B, or C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. | Participants received a single dose of placebo matched to FluBlok, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. | Total of all reporting groups |
Overall Participants | 2344 | 2304 | 4648 |
Age (Count of Participants) | |||
<=18 years |
0
0%
|
0
0%
|
0
0%
|
Between 18 and 65 years |
2344
100%
|
2304
100%
|
4648
100%
|
>=65 years |
0
0%
|
0
0%
|
0
0%
|
Sex: Female, Male (Count of Participants) | |||
Female |
1391
59.3%
|
1349
58.6%
|
2740
59%
|
Male |
953
40.7%
|
955
41.4%
|
1908
41%
|
Race/Ethnicity, Customized (Count of Participants) | |||
White/Caucasian |
1570
67%
|
1530
66.4%
|
3100
66.7%
|
Black/African-American |
430
18.3%
|
447
19.4%
|
877
18.9%
|
Latino/Hispanic |
250
10.7%
|
239
10.4%
|
489
10.5%
|
Asian |
62
2.6%
|
52
2.3%
|
114
2.5%
|
American Indian/Alaska Native |
7
0.3%
|
9
0.4%
|
16
0.3%
|
Native Hawaiian/Pacific Islander |
6
0.3%
|
8
0.3%
|
14
0.3%
|
Other-unspecified |
19
0.8%
|
19
0.8%
|
38
0.8%
|
Outcome Measures
Title | Number of Participants Reporting Solicited Injection Site (Local) Reactions |
---|---|
Description | Solicited reaction (reactogenicity event) was an adverse event (AE) that was pre-listed in electronic case report form(eCRF), considered to be related to vaccination and recorded by participant by means of memory aid. Injection sites reaction included pain,bruising,redness,swelling. Pain and bruising:Grade0: didn't have it at all; Grade1: noticed it, but it didn't interfere with usual activities at all; Grade2: had it, and it was bad enough to prevent a significant part of usual activities; Grade3: had it, and it prevented most or all of normal activities, or had to see a doctor for prescription medicine, Redness and swelling: participants measured largest diameter of any injection site reaction and grade them from 0 to 3, where Grade0: measured less than(<)10 milliliters(mm); Grade1: larger than or equal to(>=) 10mm and <20mm; Grade 2: >=20mm and <50mm; Grade3: >=50mm. Participants with multiple symptoms in same category were counted once per category using symptom with maximum grade |
Time Frame | Within 7 days post vaccination |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on safety population. |
Arm/Group Title | FluBlok (Lots A, B, C) | Placebo |
---|---|---|
Arm/Group Description | Participants received a single 0.5 mL dose of FluBlok vaccine from any of the Lots A, B, or C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. | Participants received a single dose of placebo matched to FluBlok, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. |
Measure Participants | 2344 | 2304 |
Injection site pain- Grade 0 |
1421
60.6%
|
2050
89%
|
Injection site pain- Grade 1 |
797
34%
|
177
7.7%
|
Injection site pain- Grade 2 |
52
2.2%
|
3
0.1%
|
Injection site pain- Grade 3 |
2
0.1%
|
1
0%
|
Injection site bruising- Grade 0 |
2197
93.7%
|
2172
94.3%
|
Injection site bruising- Grade 1 |
68
2.9%
|
57
2.5%
|
Injection site bruising- Grade 2 |
6
0.3%
|
1
0%
|
Injection site bruising- Grade 3 |
1
0%
|
1
0%
|
Injection site redness- Grade 0 |
2181
93%
|
2184
94.8%
|
Injection site redness- Grade 1 |
72
3.1%
|
40
1.7%
|
Injection site redness- Grade 2 |
15
0.6%
|
6
0.3%
|
Injection site redness- Grade 3 |
4
0.2%
|
1
0%
|
Injection site swelling- Grade 0 |
2195
93.6%
|
2189
95%
|
Injection site swelling- Grade 1 |
55
2.3%
|
34
1.5%
|
Injection site swelling- Grade 2 |
16
0.7%
|
6
0.3%
|
Injection site swelling- Grade 3 |
6
0.3%
|
2
0.1%
|
Title | Number of Participants Reporting Solicited Systemic Reactions |
---|---|
Description | Solicited reaction (reactogenicity event) was an AE that was pre-listed in eCRF, considered to be related to vaccination recorded by the participant by means of a memory aid between the day of vaccination (Day 0) and Day 7 post vaccination. Systemic events included fever, fatigue, shivering, joint pain, muscle pain, headache, and nausea. Fever: >=100.4 degree Fahrenheit (ºF) to <101.1ºF; >=101.2ºF to <102.2ºF; >=102.2ºF; Fatigue, shivering, joint pain, muscle pain, headache and nausea: Grade 0: didn't have it at all; Grade 1: noticed it, but it didn't interfere with usual activities at all; Grade 2: had it, and it was bad enough to prevent a significant part of usual activities; and Grade 3: had it, and it prevented most or all of normal activities, or had to see a doctor for prescription medicine. Participants with multiple symptoms in the same category were counted once per category using the symptom with the maximum grade. |
Time Frame | Within 7 days post vaccination |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on safety population. |
Arm/Group Title | FluBlok (Lots A, B, C) | Placebo |
---|---|---|
Arm/Group Description | Participants received a single 0.5 mL dose of FluBlok vaccine from any of the Lots A, B, or C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. | Participants received a single dose of placebo matched to FluBlok, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. |
Measure Participants | 2344 | 2304 |
Fever (>=100.4ºF) |
2238
95.5%
|
2188
95%
|
Fever (>=100.4 to <101.1ºF) |
8
0.3%
|
5
0.2%
|
Fever (>=101.2 to <102.2ºF) |
5
0.2%
|
6
0.3%
|
Fever (>=102.2ºF) |
4
0.2%
|
1
0%
|
Fatigue- Grade 0 |
1932
82.4%
|
1898
82.4%
|
Fatigue- Grade 1 |
250
10.7%
|
256
11.1%
|
Fatigue- Grade 2 |
78
3.3%
|
66
2.9%
|
Fatigue- Grade 3 |
12
0.5%
|
11
0.5%
|
Shivering- Grade 0 |
2202
93.9%
|
2160
93.8%
|
Shivering- Grade 1 |
52
2.2%
|
54
2.3%
|
Shivering- Grade 2 |
12
0.5%
|
13
0.6%
|
Shivering- Grade 3 |
6
0.3%
|
4
0.2%
|
Joint pain- Grade 0 |
2183
93.1%
|
2148
93.2%
|
Joint pain- Grade 1 |
69
2.9%
|
67
2.9%
|
Joint pain- Grade 2 |
14
0.6%
|
12
0.5%
|
Joint pain- Grade 3 |
6
0.3%
|
4
0.2%
|
Muscle pain- Grade 0 |
2033
86.7%
|
2077
90.1%
|
Muscle pain- Grade 1 |
197
8.4%
|
124
5.4%
|
Muscle pain- Grade 2 |
36
1.5%
|
22
1%
|
Muscle pain- Grade 3 |
6
0.3%
|
8
0.3%
|
Headache- Grade 0 |
1923
82%
|
1877
81.5%
|
Headache- Grade 1 |
264
11.3%
|
273
11.8%
|
Headache- Grade 2 |
70
3%
|
68
3%
|
Headache- Grade 3 |
15
0.6%
|
13
0.6%
|
Nausea- Grade 0 |
2143
91.4%
|
2122
92.1%
|
Nausea- Grade 1 |
94
4%
|
74
3.2%
|
Nausea- Grade 2 |
29
1.2%
|
25
1.1%
|
Nausea- Grade 3 |
6
0.3%
|
10
0.4%
|
Title | Number of Participants Reporting Unsolicited Adverse Events |
---|---|
Description | An AE was defined as any unfavorable and unintended sign (e.g., a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a study vaccine, whether or not considered to be related to the study vaccine. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination, ascertained during follow-up visit or telephone contact up to (and including) the Day 28 contact, whether reported spontaneously by the participant or in response to general questions about current or interim health status. |
Time Frame | From Day 0 (post-vaccination) through Day 28 post vaccination |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on safety population. |
Arm/Group Title | FluBlok (Lots A, B, C) | Placebo |
---|---|---|
Arm/Group Description | Participants received a single 0.5 mL dose of FluBlok vaccine from any of the Lots A, B, or C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. | Participants received a single dose of placebo matched to FluBlok, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. |
Measure Participants | 2344 | 2304 |
Count of Participants [Participants] |
61
2.6%
|
67
2.9%
|
Title | Lot Consistency: Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies Following FluBlok Vaccination |
---|---|
Description | GMTs of anti-influenza antibodies were measured using a single radial immunodiffusion (SRID) assay for 3 strains: A/Solomon Islands [H1N1], A/Wisconsin [H3N2], and B/Malaysia. Titers were expressed in terms of 1/dilution. |
Time Frame | Day 28 post vaccination |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was done on evaluable population that included all participants who had met the study entry criteria and had titers taken at Baseline (Day 0) and after vaccination (Day 28). Data for this outcome measure was planned to be collected and analyzed for each FluBlok lot separately and not planned to be collected for placebo, as pre-specified in protocol. |
Arm/Group Title | FluBlok: Lot A | FluBlok: Lot B | FluBlok: Lot C |
---|---|---|---|
Arm/Group Description | Participants received a single 0.5 mL dose of FluBlok vaccine from Lot A, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. | Participants received a single 0.5 mL dose of FluBlok vaccine from Lot B, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. | Participants received a single 0.5 mL dose of FluBlok vaccine from Lot C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. |
Measure Participants | 150 | 151 | 147 |
A/Solomon Islands (H1N1) |
346.15
|
322.95
|
381.00
|
A/Wisconsin (H3N2) |
390.34
|
192.25
|
240.01
|
B/Malaysia |
182.10
|
205.95
|
215.34
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | FluBlok (Lots A, B, C), Placebo |
---|---|---|
Comments | A/Solomon Islands (H1N1): FluBlok: Lot A versus FluBlok: Lot B | |
Type of Statistical Test | Equivalence | |
Comments | Equivalence between 2 lots for each strain was concluded if the 2-sided 95% CI for the ratio of post-vaccination GMTs for Lot A vs. B falls within 0.67 to 1.5. | |
Statistical Test of Hypothesis | p-Value | 0.009 |
Comments | Threshold for significance of p value was 0.05. | |
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | GMT ratio |
Estimated Value | 1.07 | |
Confidence Interval |
(2-Sided) 95% 0.85 to 1.36 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 2
Statistical Analysis Overview | Comparison Group Selection | FluBlok (Lots A, B, C), FluBlok: Lot C |
---|---|---|
Comments | A/Solomon Islands (H1N1): FluBlok: Lot A versus FluBlok: Lot C | |
Type of Statistical Test | Equivalence | |
Comments | Equivalence between 2 lots for each strain was concluded if the 2-sided 95% CI for the ratio of post-vaccination GMTs for Lot A vs. C falls within 0.67 to 1.5. | |
Statistical Test of Hypothesis | p-Value | 0.009 |
Comments | Threshold for significance of p value was 0.05. | |
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | GMT ratio |
Estimated Value | 0.91 | |
Confidence Interval |
(2-Sided) 0.91% 0.71 to 1.15 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 3
Statistical Analysis Overview | Comparison Group Selection | Placebo, FluBlok: Lot C |
---|---|---|
Comments | A/Solomon Islands (H1N1): FluBlok: Lot B versus FluBlok: Lot C | |
Type of Statistical Test | Equivalence | |
Comments | Equivalence between 2 lots for each strain was concluded if the 2-sided 95% CI for the ratio of post-vaccination GMTs for Lot B vs. C falls within 0.67 to 1.5. | |
Statistical Test of Hypothesis | p-Value | 0.009 |
Comments | ||
Method | ANOVA | |
Comments | Threshold for significance of p value was 0.05. | |
Method of Estimation | Estimation Parameter | GMT ratio |
Estimated Value | 0.85 | |
Confidence Interval |
(2-Sided) 95% 0.67 to 1.07 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 4
Statistical Analysis Overview | Comparison Group Selection | FluBlok (Lots A, B, C), Placebo |
---|---|---|
Comments | A/Wisconsin (H3N2): FluBlok: Lot A versus FluBlok: Lot B | |
Type of Statistical Test | Equivalence | |
Comments | Equivalence between 2 lots for each strain was concluded if the 2-sided 95% CI for the ratio of post-vaccination GMTs for Lot A vs. B falls within 0.67 to 1.5. | |
Statistical Test of Hypothesis | p-Value | 0.065 |
Comments | Threshold of significance for p value was 0.05. | |
Method | ANOVA | |
Comments | ||
Method of Estimation | Estimation Parameter | GMT ratio |
Estimated Value | 2.03 | |
Confidence Interval |
(2-Sided) 95% 1.56 to 2.64 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 5
Statistical Analysis Overview | Comparison Group Selection | FluBlok (Lots A, B, C), FluBlok: Lot C |
---|---|---|
Comments | A/Wisconsin (H3N2): FluBlok: Lot A versus FluBlok: Lot C | |
Type of Statistical Test | Equivalence | |
Comments | Equivalence between 2 lots for each strain was concluded if the 2-sided 95% CI for the ratio of post-vaccination GMTs for Lot A vs. C falls within 0.67 to 1.5. | |
Statistical Test of Hypothesis | p-Value | 0.065 |
Comments | ||
Method | ANOVA | |
Comments | Threshold of significance for p value was 0.05. | |
Method of Estimation | Estimation Parameter | GMT ratio |
Estimated Value | 1.63 | |
Confidence Interval |
(2-Sided) 95% 1.26 to 2.11 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 6
Statistical Analysis Overview | Comparison Group Selection | Placebo, FluBlok: Lot C |
---|---|---|
Comments | A/Wisconsin (H3N2): FluBlok: Lot B versus FluBlok: Lot C | |
Type of Statistical Test | Equivalence | |
Comments | Equivalence between 2 lots for each strain was concluded if the 2-sided 95% CI for the ratio of post-vaccination GMTs for Lot B vs. C falls within 0.67 to 1.5. | |
Statistical Test of Hypothesis | p-Value | 0.065 |
Comments | ||
Method | ANOVA | |
Comments | Threshold of significance for p value was 0.05. | |
Method of Estimation | Estimation Parameter | GMT ratio |
Estimated Value | 0.80 | |
Confidence Interval |
(2-Sided) 95% 0.62 to 1.04 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 7
Statistical Analysis Overview | Comparison Group Selection | FluBlok (Lots A, B, C), Placebo |
---|---|---|
Comments | B/Malaysia: FluBlok: Lot A versus FluBlok: Lot B | |
Type of Statistical Test | Equivalence | |
Comments | Equivalence between 2 lots for each strain was concluded if the 2-sided 95% CI for the ratio of post-vaccination GMTs for Lot A vs. B falls within 0.67 to 1.5. | |
Statistical Test of Hypothesis | p-Value | 0.011 |
Comments | ||
Method | ANOVA | |
Comments | Threshold of significance for p value was 0.05. | |
Method of Estimation | Estimation Parameter | GMT ratio |
Estimated Value | 0.88 | |
Confidence Interval |
(2-Sided) 95% 0.69 to 1.13 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 8
Statistical Analysis Overview | Comparison Group Selection | FluBlok (Lots A, B, C), FluBlok: Lot C |
---|---|---|
Comments | B/Malaysia: FluBlok: Lot A versus FluBlok: Lot C | |
Type of Statistical Test | Equivalence | |
Comments | Equivalence between 2 lots for each strain was concluded if the 2-sided 95% CI for the ratio of post-vaccination GMTs for Lot A vs. C falls within 0.67 to 1.5. | |
Statistical Test of Hypothesis | p-Value | 0.011 |
Comments | ||
Method | ANOVA | |
Comments | Threshold of significance for p value was 0.05. | |
Method of Estimation | Estimation Parameter | GMT ratio |
Estimated Value | 0.85 | |
Confidence Interval |
(2-Sided) 95% 0.65 to 1.09 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Statistical Analysis 9
Statistical Analysis Overview | Comparison Group Selection | Placebo, FluBlok: Lot C |
---|---|---|
Comments | B/Malaysia: FluBlok: Lot B versus FluBlok: Lot C | |
Type of Statistical Test | Equivalence | |
Comments | Equivalence between 2 lots for each strain was concluded if the 2-sided 95% CI for the ratio of post-vaccination GMTs for Lot B vs. C falls within 0.67 to 1.5. | |
Statistical Test of Hypothesis | p-Value | 0.011 |
Comments | ||
Method | ANOVA | |
Comments | Threshold of significance for p value was 0.05. | |
Method of Estimation | Estimation Parameter | GMT ratio |
Estimated Value | 0.96 | |
Confidence Interval |
(2-Sided) 95% 0.75 to 1.23 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Percentage of Participants With Positive Cell Culture/Culture-Confirmed Influenza Like Illness as Defined by Centers for Disease Control and Prevention (CDC-ILI) |
---|---|
Description | CDC-defined ILI was defined as fever (body temperature >=100ºF oral accompanied by cough and/or sore throat, on the same day or on consecutive days) due to strains represented in the vaccine. |
Time Frame | 14 days post vaccination through and up to 6 months |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on safety population. |
Arm/Group Title | FluBlok (Lots A, B, C) | Placebo |
---|---|---|
Arm/Group Description | Participants received a single 0.5 mL dose of FluBlok vaccine from any of the Lots A, B, or C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. | Participants received a single dose of placebo matched to FluBlok, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. |
Measure Participants | 2344 | 2304 |
Number [percentage of participants] |
0.04
0%
|
0.2
0%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | FluBlok (Lots A, B, C), Placebo |
---|---|---|
Comments | FluBlok versus Placebo | |
Type of Statistical Test | Superiority | |
Comments | Relative protective efficacy is equivalent to absolute efficacy which is defined as the reduction in the influenza rate for Flublok relative to placebo. | |
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Relative protective efficacy |
Estimated Value | 75.4 | |
Confidence Interval |
(2-Sided) 95% -148.0 to 99.5 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | Percentage of Participants With Seroprotection to Influenza Vaccine Antigens After Vaccination With FluBlok |
---|---|
Description | Anti-influenza antibodies were measured using an HAI assay for 3 strains: A/Solomon Islands [H1N1], A/Wisconsin [H3N2] and B/Malaysia. Seroprotection was defined as a post-vaccination HAI antibody titer of >=1:40. |
Time Frame | 28 days post vaccination |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on evaluable population. Data for this outcome measure was not planned to be collected and analyzed for placebo group, as pre-specified in protocol. |
Arm/Group Title | FluBlok (Lots A, B, C) |
---|---|
Arm/Group Description | Participants received a single 0.5 mL dose of FluBlok vaccine from any of the Lots A, B, or C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. |
Measure Participants | 448 |
A/Solomon Islands (H1N1) |
99
4.2%
|
A/Wisconsin (H3N2) |
97
4.1%
|
B/Malaysia |
96
4.1%
|
Title | Percentage of Participants With Seroconversion to Influenza Vaccine Antigens After Vaccination With FluBlok |
---|---|
Description | Anti-influenza antibodies were measured using an HAI assay for 3 strains: A/Solomon Islands [H1N1], A/Wisconsin [H3N2] and B/Malaysia. Seroconversion was defined as a post-vaccination titer of >=1:40 in participants with undetectable baseline antibody (HI titer = <1:10) or a >=4-fold rise in antibody in participants with a baseline titer of >=1:10, with the achievement of post-vaccination titer of at least 1:40. |
Time Frame | 28 days post vaccination |
Outcome Measure Data
Analysis Population Description |
---|
Analysis was performed on evaluable population. Data for this outcome measure was not planned to be collected and analyzed for placebo group, as pre-specified in protocol. |
Arm/Group Title | FluBlok (Lots A, B, C) |
---|---|
Arm/Group Description | Participants received a single 0.5 mL dose of FluBlok vaccine from any of the Lots A, B, or C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. |
Measure Participants | 448 |
A/Solomon Islands (H1N1) |
78
3.3%
|
A/Wisconsin (H3N2) |
81
3.5%
|
B/Malaysia |
52
2.2%
|
Adverse Events
Time Frame | Unsolicited non-serious AEs: Day 0 to Day 28 post vaccination, Solicited reactions: within 7 days post vaccination, SAE: through the end of influenza season (up to 6 months) | |||
---|---|---|---|---|
Adverse Event Reporting Description | Solicited reaction was AE that was prelisted (i.e., solicited) in the eCRF and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination. Analysis was performed on Safety population. | |||
Arm/Group Title | FluBlok (Lots A, B, C) | Placebo | ||
Arm/Group Description | Participants received a single 0.5 mL dose of FluBlok vaccine from any of the Lots A, B, or C, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. | Participants received a single dose of placebo matched to FluBlok, intramuscularly on Day 0 (Visit 1). Participants were followed up to 6 months after vaccination. | ||
All Cause Mortality |
||||
FluBlok (Lots A, B, C) | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 1/2344 (0%) | 1/2304 (0%) | ||
Serious Adverse Events |
||||
FluBlok (Lots A, B, C) | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 30/2344 (1.3%) | 34/2304 (1.5%) | ||
Blood and lymphatic system disorders | ||||
Iron deficiency anaemia | 1/2344 (0%) | 0/2304 (0%) | ||
Lymphadenopathy | 0/2344 (0%) | 1/2304 (0%) | ||
Cardiac disorders | ||||
Angina pectoris | 1/2344 (0%) | 0/2304 (0%) | ||
Myocardial infarction | 0/2344 (0%) | 1/2304 (0%) | ||
Pericardial effusion | 1/2344 (0%) | 0/2304 (0%) | ||
Sinus tachycardia | 1/2344 (0%) | 0/2304 (0%) | ||
Supraventricular tachycardia | 0/2344 (0%) | 1/2304 (0%) | ||
Congenital, familial and genetic disorders | ||||
Rathke's cleft cyst | 0/2344 (0%) | 1/2304 (0%) | ||
Eye disorders | ||||
Retinal haemorrhage | 1/2344 (0%) | 0/2304 (0%) | ||
Gastrointestinal disorders | ||||
Abdominal pain | 1/2344 (0%) | 1/2304 (0%) | ||
Crohn's disease | 0/2344 (0%) | 1/2304 (0%) | ||
Inflammatory bowel disease | 0/2344 (0%) | 1/2304 (0%) | ||
Small intestinal obstruction | 1/2344 (0%) | 0/2304 (0%) | ||
Vomiting | 1/2344 (0%) | 0/2304 (0%) | ||
General disorders | ||||
Accidental death | 0/2344 (0%) | 1/2304 (0%) | ||
Chest pain | 0/2344 (0%) | 1/2304 (0%) | ||
Non-cardiac chest pain | 1/2344 (0%) | 0/2304 (0%) | ||
Hepatobiliary disorders | ||||
Biliary colic | 0/2344 (0%) | 1/2304 (0%) | ||
Cholelithiasis | 1/2344 (0%) | 0/2304 (0%) | ||
Infections and infestations | ||||
Appendicitis | 1/2344 (0%) | 2/2304 (0.1%) | ||
Cellulitis | 0/2344 (0%) | 1/2304 (0%) | ||
Hepatitis viral | 1/2344 (0%) | 0/2304 (0%) | ||
Infected insect bite | 0/2344 (0%) | 1/2304 (0%) | ||
Infectious mononucleosis | 0/2344 (0%) | 1/2304 (0%) | ||
Kidney infection | 0/2344 (0%) | 2/2304 (0.1%) | ||
Perianal abscess | 0/2344 (0%) | 1/2304 (0%) | ||
Peritonsillar abscess | 0/2344 (0%) | 1/2304 (0%) | ||
Pharyngitis streptococcal | 0/2344 (0%) | 1/2304 (0%) | ||
Pneumonia | 0/2344 (0%) | 1/2304 (0%) | ||
Postoperative infection | 0/2344 (0%) | 1/2304 (0%) | ||
Pyelonephritis acute | 1/2344 (0%) | 0/2304 (0%) | ||
Staphylococcal abscess | 0/2344 (0%) | 1/2304 (0%) | ||
Tonsillitis | 1/2344 (0%) | 0/2304 (0%) | ||
Injury, poisoning and procedural complications | ||||
Acetabulum fracture | 1/2344 (0%) | 0/2304 (0%) | ||
Cervical vertebral fracture | 1/2344 (0%) | 0/2304 (0%) | ||
Fibula fracture | 1/2344 (0%) | 0/2304 (0%) | ||
Hand fracture | 1/2344 (0%) | 0/2304 (0%) | ||
Head injury | 0/2344 (0%) | 1/2304 (0%) | ||
Injury | 1/2344 (0%) | 0/2304 (0%) | ||
Ligament injury | 1/2344 (0%) | 0/2304 (0%) | ||
Open fracture | 1/2344 (0%) | 0/2304 (0%) | ||
Tibia fracture | 1/2344 (0%) | 0/2304 (0%) | ||
Metabolism and nutrition disorders | ||||
Dehydration | 0/2344 (0%) | 2/2304 (0.1%) | ||
Hyperglycaemic hyperosmolar nonketotic syndrome | 0/2344 (0%) | 1/2304 (0%) | ||
Musculoskeletal and connective tissue disorders | ||||
Aseptic necrosis bone | 1/2344 (0%) | 0/2304 (0%) | ||
Back pain | 1/2344 (0%) | 0/2304 (0%) | ||
Intervertebral disc protrusion | 0/2344 (0%) | 2/2304 (0.1%) | ||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
Breast cancer | 0/2344 (0%) | 1/2304 (0%) | ||
Liposarcoma | 1/2344 (0%) | 0/2304 (0%) | ||
Uterine leiomyoma | 2/2344 (0.1%) | 0/2304 (0%) | ||
Nervous system disorders | ||||
Headache | 0/2344 (0%) | 1/2304 (0%) | ||
Hypoaesthesia | 1/2344 (0%) | 0/2304 (0%) | ||
Pregnancy, puerperium and perinatal conditions | ||||
Ectopic pregnancy | 0/2344 (0%) | 1/2304 (0%) | ||
Pregnancy induced hypertension | 0/2344 (0%) | 1/2304 (0%) | ||
Psychiatric disorders | ||||
Adjustment disorder | 1/2344 (0%) | 0/2304 (0%) | ||
Bipolar disorder | 1/2344 (0%) | 0/2304 (0%) | ||
Depression | 0/2344 (0%) | 3/2304 (0.1%) | ||
Suicidal ideation | 0/2344 (0%) | 1/2304 (0%) | ||
Suicide attempt | 2/2344 (0.1%) | 1/2304 (0%) | ||
Depression | 0/2344 (0%) | 1/2304 (0%) | ||
Renal and urinary disorders | ||||
Nephrolithiasis | 0/2344 (0%) | 1/2304 (0%) | ||
Reproductive system and breast disorders | ||||
Adnexa uteri mass | 1/2344 (0%) | 0/2304 (0%) | ||
Dysfunctional uterine bleeding | 1/2344 (0%) | 0/2304 (0%) | ||
Dysmenorrhoea | 1/2344 (0%) | 1/2304 (0%) | ||
Dyspareunia | 0/2344 (0%) | 1/2304 (0%) | ||
Endometrial disorder | 1/2344 (0%) | 0/2304 (0%) | ||
Menometrorrhagia | 0/2344 (0%) | 1/2304 (0%) | ||
Menorrhagia | 1/2344 (0%) | 0/2304 (0%) | ||
Ovarian cyst | 1/2344 (0%) | 0/2304 (0%) | ||
Uterine haemorrhage | 1/2344 (0%) | 0/2304 (0%) | ||
Uterine prolapse | 0/2344 (0%) | 1/2304 (0%) | ||
Prolapsed bladder | 1/2344 (0%) | 0/2304 (0%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Pleural effusion | 1/2344 (0%) | 0/2304 (0%) | ||
Pulmonary embolism | 1/2344 (0%) | 0/2304 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
FluBlok (Lots A, B, C) | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 152/2344 (6.5%) | 120/2304 (5.2%) | ||
Nervous system disorders | ||||
Headache | 35/2344 (1.5%) | 42/2304 (1.8%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Cough | 48/2344 (2%) | 37/2304 (1.6%) | ||
Nasal congestion | 37/2344 (1.6%) | 31/2304 (1.3%) | ||
Pharyngolaryngeal pain | 42/2344 (1.8%) | 49/2304 (2.1%) |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications.
Results Point of Contact
Name/Title | Trial Transparency Team |
---|---|
Organization | Sanofi Pasteur |
Phone | 800-633-1610 ext 1# |
Contact-US@sanofi.com |
- PSC04