The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product. Before prescribing any product mentioned in this Register, healthcare professionals should consult prescribing information for the product approved in their country. Study No.: SPD707-104 (Flu-Laval-104) Title: A Phase II randomized study to evaluate the immunogenicity, safety and tolerance of three formulations of Fluviral S/F influenza vaccine and Vaxigrip in healthy adults 50-64 years of age and 65 years of age. Fluviral S/F: ID Biomedical s* trivalent split-virion influenza vaccine (FluSF). Vaxigrip : Sanofi-Pasteur s trivalent split-virion inactivated influenza vaccine (Vax). *ID Biomedical has been taken over by GlaxoSmithKline Biologicals. Rationale: The aim of this study was to evaluate the immunogenicity of 3 formulations of FluSF compared to Vax. All vaccines in the trial were formulated with virus strains recommended for the 2004-2005 influenza season. Phase: II Study Period: 11 October 2004 to 04 June 2005 Study Design: A randomized, double-blind, active controlled, multicenter study with 2 age groups, each divided in 4 treatment groups (1:1:1:1). Centers: 10 study centers in Canada Indication: Immunization against influenza disease in subjects aged 50 to 64 years and elderly aged 65 years and older Treatment: The study groups were as follows: Group A: subjects received FluSF, : subjects received filtered formulation of FluSF, : subjects received filtered and thimerosal-reduced formulation of FluSF, : subjects received Vax. Subjects were administered one intra-muscular dose into the deltoid muscle of the non-dominant arm. Objectives: To describe the immunogenicity, as assessed by serum hemagglutination inhibition (HAI) titers, of FluSF sterilefiltered formulations and comparator products based on: Seroconversion rates (at least a four-fold rise in reciprocal titer or change from undetectable (< 10) to a reciprocal titer of 40); Seroprotection rates (Day 21 HAI reciprocal titer of 40, regardless of pre-immunization level); Geometric mean reciprocal titers; Geometric mean fold-rise in titer (GMFR); To compare sterile-filtered FluSF results with published Committee for Proprietary Medicinal Products (CPMP) criteria for the seroconversion, seroprotection, and GMFR. Primary Outcome/Efficacy Variable: Immunogenicity: For each of the 3 viral antigens separately in the 4 treatment groups and in the pooled group receiving FluSF sterilefiltered formulations (groups B plus C) seroconversion* rate seroprotection** rate Geometric mean fold-rise (GMFR***) in HAI titer *Seroconversion is defined as either a 4-fold increase in reciprocal HAI titer post-vaccination (Day 21) compared to prevaccination (Day 0) or a rise of undetectable HAI titer (i.e., <10) pre-vaccination (Day 0) to an HAI titer 40 postvaccination (Day 21) ** Seroprotection is defined as a HAI titer 40 at Day 21 post-vaccination ***GMFR is defined as the ratio of post-vaccination (Day 21) Geometric Mean Titer (GMT) to the pre-vaccination (Day 0) Geometric Mean Titer (GMT). Secondary Outcome/Efficacy Variable(s): Safety: Frequency and severity of adverse events (AEs) through 6 months post-immunization, including solicited local and systemic vaccine reactions from Day 0 to Day 3. Severity data were not readily available in the report for unsolicited AEs.
Statistical Methods: The analyses were performed on the Total Vaccinated cohort and the According-To-Protocol (ATP) for immunogenicity. - The Total Vaccinated cohort included all subjects who received the study vaccine. - The ATP cohort for immunogenicity included all vaccinated subjects who complied with the procedures defined in the protocol and for whom immunogenicity data were available. Analysis of immunogenicity: The analysis of immunogenicity was performed on the ATP cohort for immunogenicity. Geometric mean titers (GMTs) and seroprotection rates for each vaccine strain were computed at pre- and postvaccination for each vaccine group and for each age group with 95% confidence intervals (CIs). Seroconversion rates and GMFR for each vaccine strain were computed at post-vaccination for each vaccine group and each age group. The 95% CIs were also calculated for seroconversion rate, the lower limit for the 95%CI was calculated for GMFR. According to a CBER request, the results of immunogenicity for all study population including subjects below 60 were evaluated by comparison with the European Union (EU) requirements for Influenza vaccines [Committee for Proprietary Medicinal Products (CPMP)] for elderly population. The CPMP standards for elderly vaccinees are for each vaccine strain, the lower 95% confidence bound for : - seroconversion rate : 30% - seroprotection rate : 60% - GMFR : 2 Analysis of safety: The analysis of safety was performed on the Total Vaccinated cohort. For each solicited symptom, the percentage of subjects with solicited symptom was summarized for each vaccine group 30 minutes after vaccine dose and during 4 days (Day 0-3) follow-up period after vaccination. The percentage of subjects reporting unsolicited AEs within 22 days (Day 0-21) and 6 months following administration of vaccine(s) was tabulated according to the Medical Dictionary for Regulatory Activities (MedDRA) preferred term for each vaccine group. The occurrence of serious adverse events (SAEs) was tabulated according to the MedDRA preferred term for each vaccine group during the entire study period including a long-term safety follow-up period of 6 months. Study Population: Healthy male or female adults (50-64 years of age or elderly 65 years of age) who passed a satisfactory medical assessment with no clinically significant and/or relevant abnormalities (medical and concomitant medication history, physical examination). If the subject was female and of childbearing potential, she had to be abstinent or to have used contraceptive precautions for 30 days prior to vaccination. Subjects had to understand and be able, willing and likely to fully comply with study procedures and restrictions. Written informed consent was obtained prior to study entry. Subjects who received an influenza vaccine within 6 months prior to dosing were excluded. Age group: 50-64 years old Number of Subjects: Group A Planned, N Not Available Not Available Not Available Not Available Randomized, N (Total 88 86 89 91 Completed, n (%) 86 (97.7) 85 (98.8) 87 (97.8) 90 (98.9) Total Number Subjects Withdrawn, n (%) 2 (2.3) 1 (1.2) 2 (2.2) 1 (1.1) Withdrawn due to Adverse Events, n (%) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Withdrawn due to Lack of Efficacy, n (%) Not Applicable Not Applicable Not Applicable Not Applicable Withdrawn for other reasons, n (%) 2 (2.3) 1 (1.2) 2 (2.2) 1 (1.1) Demographics Group A N (Total 88 86 89 91 Females: Males 56:32 56:30 44:45 59:32 Mean Age, years (SD) 57 (4) 57 (4) 57 (4) 58 (4) Caucasian, n (%) 80 (90.9) 80 (93.0) 86 (96.6) 89 (97.8) Age group: 65 years old Number of Subjects: Group A Planned, N Not Available Not Available Not Available Not Available Randomized, N (Total 76 77 76 75 Completed, n (%) 75 (98.7) 75 (97.4) 76 (100) 75 (100) Total Number Subjects Withdrawn, n (%) 1 (1.3) 2 (2.6) 0 (0.0) 0 (0.0) Withdrawn due to Adverse Events, n (%) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Withdrawn due to Lack of Efficacy, n (%) Not Applicable Not Applicable Not Applicable Not Applicable Withdrawn for other reasons, n (%) 1 (1.3) 2 (2.6) 0 (0.0) 0 (0.0)
Demographics Group A N (Total 76 77 76 75 Females: Males 41:35 42:35 38:38 38:37 Mean Age, years (SD) 71 (6) 69 (4) 70 (5) 70 (5) Caucasian, n (%) 74 (97.4) 73 (94.8) 74 (97.4) 75 (100) Primary Efficacy Results: Seroprotection rates and GMTs for each vaccine strain (ATP cohort for immunogenicity) Strain Group Timing N GMT 40 Value 95% CI n % 95% CI* LL UL LL 50-64 years old A/Wyoming (H3N2) A/Caledonia (H1N1) A Pre 88 40.64 29.63 55.72 53 60.23 - Post 88 431.66 349.96 532.44 87 98.86 96.65 B Pre 85 44.47 32.13 61.55 54 63.53 - Post 85 436.24 348.19 546.56 84 98.82 96.53 C Pre 88 47.94 35.46 64.82 57 64.77 - Post 88 431.66 345.57 539.20 87 98.86 96.65 B&C Pre 173 46.21 37.11 57.54 111 64.16 - Post 173 433.90 370.95 507.54 171 98.84 97.25 D Pre 90 37.61 27.46 51.50 49 54.44 - Post 90 435.45 346.19 547.73 88 97.78 94.73 A Pre 88 18.20 14.14 23.41 29 32.95 - Post 88 92.91 72.48 119.12 78 88.64 82.01 B Pre 85 16.58 12.90 21.31 26 30.59 - Post 85 106.42 81.22 139.46 75 88.24 81.39 C Pre 88 20.16 15.77 25.77 32 36.36 - Post 88 103.75 78.54 137.05 77 87.50 80.59 B&C Pre 173 18.31 15.38 21.80 58 33.53 - Post 173 105.05 86.68 127.32 152 87.86 82.99 D Pre 90 16.37 12.91 20.76 31 34.44 - Post 90 123.14 95.40 158.95 82 91.11 85.23 B/Jiangsu A Pre 88 7.36 6.27 8.63 6 6.82 - Post 88 27.84 21.22 36.54 45 51.14 40.69 B Pre 85 6.76 5.92 7.73 3 3.53 - Post 85 28.87 21.47 38.81 40 47.06 36.45 C Pre 88 7.07 6.14 8.14 6 6.82 - Post 88 29.89 22.42 39.84 44 50.00 39.55 B&C Pre 173 6.92 6.28 7.62 9 5.20 - Post 173 29.38 23.96 36.04 84 48.55 41.11 D Pre 90 7.84 6.66 9.21 9 10.00 - Post 90 41.25 30.56 55.68 53 58.89 48.72 65 years old A/Wyoming (H3N2) A/Caledonia (H1N1) A Pre 76 61.41 45.27 83.30 55 72.37 - Post 76 420.70 336.74 525.61 76 100 100 B Pre 75 55.79 41.70 74.65 55 73.33 - Post 75 406.92 331.30 499.80 75 100 100 C Pre 76 60.85 43.60 84.92 54 71.05 - Post 76 363.58 285.36 463.24 75 98.68 96.12 B&C Pre 151 58.28 46.82 72.56 109 72.19 - Post 151 384.50 328.48 450.07 150 99.34 98.04 D Pre 75 74.99 56.74 99.11 58 77.33 - Post 75 434.11 354.78 531.18 75 100 100 A Pre 76 30.70 24.36 38.69 43 56.58 - Post 76 87.64 70.33 109.20 68 89.47 82.57 B Pre 75 26.15 20.59 33.20 37 49.33 -
Post 75 89.38 69.51 114.95 67 89.33 82.35 C Pre 76 25.82 20.64 32.29 33 43.42 - Post 76 75.05 58.47 96.34 61 80.26 71.31 B&C Pre 151 25.98 22.10 30.54 70 46.36 - Post 151 81.86 68.67 97.58 128 84.77 79.04 D Pre 75 26.64 20.54 34.53 35 46.67 - Post 75 94.48 75.19 118.71 69 92.00 85.86 B/Jiangsu A Pre 76 10.37 8.37 12.86 11 14.47 - Post 76 52.11 38.37 70.77 51 67.11 56.54 B Pre 75 10.87 8.77 13.47 13 17.33 - Post 75 64.68 51.47 81.29 58 77.33 67.86 C Pre 76 10.00 8.17 12.24 11 14.47 - Post 76 42.25 31.15 57.30 43 56.58 45.44 B&C Pre 151 10.42 9.01 12.06 24 15.89 - Post 151 52.20 43.10 63.23 101 66.89 59.38 D Pre 75 9.29 7.69 11.21 8 10.67 - Post 75 68.37 50.73 92.14 56 74.67 64.82 N = Number of subjects with available results n (%) = number (percentage) of subjects with antibody titers specified value Pre = Pre-vaccination at Day 0 Post = Post-vaccination at Day 21 95% CI = 95% confidence interval ; LL = lower limit, UL = upper limit * 95% confidence interval on the point estimate of % seroprotected derived by the normal approximation to the binomial. CPMP criteria [EU requirement for the seroprotection rates (post-vaccination)] for elderly vaccinees : 60% Seroconversion rates and geometric mean fold rise (GMFR) for each vaccine strain at post-vaccination (ATP cohort for immunogenicity) Strain Group N Seroconversion rate GMFR n % 95% CI Value 95% CI LL LL A/Wyoming (H3N2) A/Caledonia (H1N1) 50-64 years old A 88 63 71.59 62.17 10.62 7.63 B 85 65 76.47 67.45 9.81 7.11 C 88 62 70.45 60.92 9.00 6.50 B&C 173 127 73.41 66.83 9.39 7.48 D 90 67 74.44 65.43 11.58 8.14 A 88 48 54.55 44.14 5.11 3.76 B 85 49 57.65 47.14 6.42 4.62 C 88 44 50.00 39.55 5.15 3.78 B&C 173 93 53.76 46.33 5.74 4.59 D 90 54 60.00 49.88 7.52 5.47 B/Jiangsu A 88 39 44.32 33.94 3.79 3.00 B 85 35 41.18 30.71 4.27 3.20 C 88 40 45.45 35.05 4.23 3.24 B&C 173 75 43.35 35.97 4.25 3.50 D 90 48 53.33 43.03 5.26 3.92 65 years old A/Wyoming (H3N2) A/Caledonia (H1N1) A 76 53 69.74 59.41 6.85 5.00 B 75 51 68.00 57.44 7.29 5.26 C 76 46 60.53 49.54 5.98 4.30 B&C 151 97 64.24 56.59 6.60 5.24 D 75 50 66.67 56.00 5.79 4.39 A 76 24 31.58 21.13 2.85 2.28 B 75 27 36.00 25.14 3.42 2.51 C 76 25 32.89 22.33 2.91 2.22
B&C 151 52 34.44 26.86 3.15 2.57 D 75 34 45.33 34.07 3.55 2.71 B/Jiangsu A 76 42 55.26 44.08 5.02 3.81 B 75 47 62.67 51.72 5.95 4.73 C 76 37 48.68 37.45 4.22 3.33 B&C 151 84 55.63 47.70 5.01 4.24 D 75 49 65.33 54.56 7.36 5.45 N = Number of subjects with available results n (%) = number (percentage) of responders 95% CI = 95% confidence interval ; LL = lower limit * 95% confidence interval on the point estimate of seroconversion for each vaccine, derived by the normal approximation to the binomial. CPMP criteria [EU requirement (post-vaccination)] for elderly vaccinees: - for seroconversion rate: 30% - for GMFR: 2.0 Number and percentage of subjects reporting local immediate complaints* within 30 minutes after vaccination (Total Symptom Intensity Group A n % n % n % n % Any 0 0.0 2 1.2 0 0.0 1 0.6 Limited arm mobility Pain Any 3 1.8 6 3.7 9 5.5 6 3.6 Redness Any 8 4.9 10 6.1 8 4.8 11 6.6 > 50 mm 0 0.0 0 0.0 0 0.0 0 0.0 Swelling Any 7 4.3 4 2.5 1 0.6 3 1.8 > 50 mm 0 0.0 0 0.0 0 0.0 0 0.0 N = number of subjects with a symptom sheet completed n (%) = number (percentage) of subjects for whom the symptom was reported Any = incidence of a specified solicited local symptom irrespective of intensity grade Grade 3 = that prevented activities of daily living For one subject of this vaccine group, information about redness or swelling symptom was not collected. * Immediate complaints = solicited reactions present at the 30-minute observation period and resolved within 2 hours after vaccination, these are considered article-related. Number and percentage of subjects reporting general immediate complaints* within 30 minutes after vaccination (Total Symptom Intensity Group A n % n % n % n % Chest tightness Any 0 0.0 0 0.0 0 0.0 1 0.6 Chills Any 1 0.6 0 0.0 1 0.6 0 0.0 Cough Any 1 0.6 0 0.0 1 0.6 1 0.6 Difficulty in Any 0 0.0 0 0.0 0 0.0 0 0.0 breathing Facial swelling Any 0 0.0 0 0.0 0 0.0 0 0.0 Fatigue Any 1 0.6 1 0.6 0 0.0 0 0.0 Fever > 38.0 C 0 0.0 0 0.0 0 0.0 0 0.0 > 40.0 C 0 0.0 0 0.0 0 0.0 0 0.0
Headache Any 1 0.6 1 0.6 3 1.8 1 0.6 Joint pain Any 0 0.0 0 0.0 0 0.0 0 0.0 Low body temperature Malaise Any 0 0.0 1 0.6 0 0.0 0 0.0 Muscle aches Any 1 0.6 1 0.6 2 1.2 1 0.6 < 35.8 C 16 9.8 16 9.8 23 13.9 21 12.7 < 30.0 C 0 0.0 0 0.0 0 0.0 0 0.0 Nausea, vomiting, Any 0 0.0 0 0.0 0 0.0 0 0.0 diarrhea Red eyes Any 0 0.0 0 0.0 0 0.0 0 0.0 Sore throat Any 0 0.0 0 0.0 0 0.0 0 0.0 Wheeze Any 0 0.0 0 0.0 0 0.0 0 0.0 N = number of subjects with a symptom sheet completed n (%) = number (percentage) of subjects for whom the symptom was reported Any = incidence of a specified solicited general symptom irrespective of intensity grade Grade 3 = that prevented activities of daily living For 3 subjects of this vaccine group, information about fever or low body temperature symptom was not collected. * Immediate complaints = solicited reactions present at the 30-minute observation period and resolved within 2 hours after vaccination, these were considered as related to the vaccination. Number and percentage of subjects reporting solicited local symptoms* within 4 days (Day 0-3) after vaccination (Total Symptom Intensity Group A n % n % n % n % Any 9 5.5 16 9.8 9 5.5 12 7.2 Limited arm mobility Pain Any 40 24.4 37 22.7 33 20.0 39 23.5 Redness Any 19 11.6 29 17.8 19 11.5 20 12.0 > 50 mm 0 0.0 0 0.0 0 0.0 0 0.0 Swelling Any 15 9.1 15 9.2 6 3.6 12 7.2 > 50 mm 0 0.0 0 0.0 0 0.0 1 0.6 N = number of subjects with a symptom sheet completed n (%) = number (percentage) of subjects for whom the symptom was reported Any = incidence of a specified solicited local symptom irrespective of intensity grade Grade 3 = that prevented activities of daily living * Solicited symptoms = solicited reactions with onset more than 2 hours after vaccination and resolution before Day 4 post-vaccination. These were considered test article-related. Primary Efficacy Results: Number and percentage of subjects reporting solicited general symptoms* within 4 days (Day 0-3) after vaccination (Total Symptom Intensity Group A n % n % n % n % Chest tightness Any 3 1.8 5 3.1 1 0.6 4 2.4 Chills Any 8 4.9 6 3.7 4 2.4 9 5.4 Grade 3 0 0.0 0 0.0 0 0.0 1 0.6 Cough Any 6 3.7 5 3.1 6 3.6 6 3.6
Grade 3 1 0.6 0 0.0 0 0.0 0 0.0 Difficulty in Any 1 0.6 4 2.5 2 1.2 3 1.8 breathing Facial swelling Any 2 1.2 0 0.0 1 0.6 3 1.8 Fatigue Any 14 8.5 20 12.3 13 7.9 17 10.2 Grade 3 0 0.0 2 1.2 1 0.6 2 1.2 Fever > 38.0 C 0 0.0 0 0.0 1 0.6 3 1.8 > 40.0 C 0 0.0 0 0.0 0 0.0 0 0.0 Flu-like symptoms Any 1 0.6 1 0.6 0 0.0 1 0.6 Headache Any 17 10.4 18 11.0 16 9.7 18 10.8 Grade 3 0 0.0 1 0.6 1 0.6 1 0.6 Joint pain Any 9 5.5 12 7.4 8 4.8 9 5.4 Grade 3 0 0.0 1 0.6 0 0.0 1 0.6 Low body temperature < 35.8 C 32 19.5 33 20.2 33 20.0 34 20.5 < 30.0 C 0 0.0 0 0.0 0 0.0 0 0.0 Malaise Any 10 6.1 8 4.9 5 3.0 7 4.2 Grade 3 0 0.0 0 0.0 1 0.6 0 0.0 Muscle aches Any 17 10.4 18 11.0 17 10.3 17 10.2 Grade 3 0 0.0 0 0.0 1 0.6 1 0.6 Nausea, vomiting, Any 10 6.1 14 8.6 5 3.0 9 5.4 diarrhea Grade 3 0 0.0 0 0.0 0 0.0 1 0.6 Red eyes Any 3 1.8 8 4.9 2 1.2 4 2.4 Grade 3 1 0.6 0 0.0 0 0.0 0 0.0 Sore throat Any 5 3.0 9 5.5 8 4.8 8 4.8 Wheeze Any 2 1.2 1 0.6 1 0.6 2 1.2 Grade 3 0 0.0 1 0.6 0 0.0 0 0.0 N = number of subjects with a symptom sheet completed n (%) = number (percentage) of subjects for whom the symptom was reported Any = incidence of a specified general symptom irrespective of intensity grade Grade 3 = that prevented activities of daily living. * Solicited symptoms = solicited reactions with onset more than 2 hours after vaccination and resolution before Day 4 post-vaccination. These were considered as related to the vaccination. Not Applicable. Safety Results: Number (%) of subjects with unsolicited adverse events within 21 days after vaccination (Total Most Frequent Adverse Events - On-Therapy- (occurring within Day 0-21 following vaccination) Group A Subjects with any AE(s), n (%) 67 (40.9) 84 (51.5) 73 (44.2) 79 (47.6) Headache 9 (5.5) 15 (9.2) 22 (13.3) 14 (8.4) Pharyngolaryngeal pain 6 (3.7) 8 (4.9) 8 (4.8) 11 (6.6) Injection site erythema 6 (3.7) 10 (6.1) 8 (4.8) 8 (4.8) Cough 8 (4.9) 5 (3.1) 10 (6.1) 7 (4.2) Injection site pain 8 (4.9) 8 (4.9) 6 (3.6) 8 (4.8) Myalgia 2 (1.2) 8 (4.9) 9 (5.5) 5 (3.0) Arthralgia 3 (1.8) 9 (5.5) 5 (3.0) 6 (3.6) Fatigue 4 (2.4) 4 (2.5) 10 (6.1) 5 (3.0) Safety Results: Number (%) of subjects with unsolicited adverse events from vaccine administration up to 6 months after vaccination(total
Most Frequent Adverse Events - On-Therapy- (occurring within Month 0-6 following vaccination) Group A Subjects with any AE(s), n (%) 125 (76.2%) 128 (78.5%) 130 (78.8%) 130 (78.3%) Headache 28 (17.1) 31 (19.0) 32 (19.4) 30 (18.1) Cough 17 (10.4) 23 (14.1) 25 (15.2) 24 (14.5) Pharyngolaryngeal pain 20 (12.2) 19 (11.7) 19 (11.5) 20 (12.0) Rhinorrhea 14 (8.5) 17 (10.4) 18 (10.9) 17 (10.2) Upper respiratory tract infection nos 10 (6.1) 17 (10.4) 13 (7.9) 16 (9.6) Arthralgia 5 (3.0) 12 (7.4) 15 (9.1) 12 (7.2) Nasal congestion 14 (8.5) 9 (5.5) 7 (4.2) 5 (3.0) Safety Results: Number (%) of subjects with Serious Adverse Events (SAEs) during the entire study period up to 6 months after vaccination (Total Serious adverse event, n (%) [n considered by the investigator to be related to study medication] All SAEs Group A Subjects with any SAE(s), n (%)[related] 2 (1.2) [0] 2 (1.2) [0] 6 (3.6) [0] 4 (2.4) [0] Myocardial infarction 0 (0.0) [0] 0 (0.0) [0] 2 (1.2) [0] 0 (0.0) [0] Acute coronary syndrome 0 (0.0) [0] 0 (0.0) [0] 1 (0.6) [0] 0 (0.0) [0] Ankle fracture 0 (0.0) [0] 0 (0.0) [0] 1 (0.6) [0] 0 (0.0) [0] Anxiety 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (0.6) [0] Atrial fibrillation 0 (0.0) [0] 0 (0.0) [0] 1 (0.6) [0] 0 (0.0) [0] Bradycardia nos 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (0.6) [0] Breast cancer nos 0 (0.0) [0] 0 (0.0) [0] 1 (0.6) [0] 0 (0.0) [0] Cardiac procedure complication 0 (0.0) [0] 0 (0.0) [0] 1 (0.6) [0] 0 (0.0) [0] Cerebrovascular accident 1 (0.6) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] Chest pain 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (0.6) [0] Cystocele 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (0.6) [0] Deep vein thrombosis 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (0.6) [0] Dizziness 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (0.6) [0] Endometrial cancer stage I 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (0.6) [0] Lobar pneumonia nos 1 (0.6) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] Lung cancer stage unspecified 1 (0.6) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] Prostatism 0 (0.0) [0] 1 (0.6) [0] 0 (0.0) [0] 0 (0.0) [0] Pulmonary embolism 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (0.6) [0] Stress incontinence 0 (0.0) [0] 1 (0.6) [0] 0 (0.0) [0] 0 (0.0) [0] Syncope 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 1 (0.6) [0] Fatal SAEs Group A Subjects with fatal SAEs, n (%) [related] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] 0 (0.0) [0] Conclusion: At Day 21, at least 97.78%, 87.50% and 47.06% of the subjects between 50-64 years of age had HAI titers 40 for A/Wyoming, A/Caledonia and B/Jiangsu vaccine strains, respectively. At the same time point, at least 98.68%, 80.26% and 56.58% of the subjects 65 years of age had HAI titers 40 for A/Wyoming, A/Caledonia and B/Jiangsu vaccine strains, respectively. In all groups, redness was the most frequently reported local immediate complaint while pain at the injection site was the most frequently reported solicited local symptom (Day 0-3). Low body temperature was the most frequently reported solicited general immediate complaint and symptom in all groups. At least one unsolicited AE was reported between Day 0 and 21 by 67 (40.9%), 84 (51.5%), 73 (44.2%) and 79 (47.6%) subjects of the Groups A-D, respectively. Between Month 0 and Month 6, unsolicited AEs were reported by 125 (76.2%), 128 (78.5%), 130 (78.8%) and 130 (78.3%) subjects of the Groups A-D, respectively. SAEs were reported by 14 subjects (2 in Group A, 2 in Group B, 6 in, and 4 in ). These SAEs were considered by the investigators to be not related to the study vaccination. No fatal SAEs were reported. Date Updated: 20-May-2015