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. GSK Medicine: Fluarix Quadrivalent (GSK2321138A) Study Number: 116023 (FLU D-QIV-009 EXT 004) Title: Immunogenicity, safety and reactogenicity study of GSK Biologicals’ quadrivalent seasonal influenza candidate vaccine GSK2321138A, administered to children who previously participated in study 115345. GSK2321138A (FLU D-QIV): GlaxoSmithKline (GSK) Biologicals’ quadrivalent seasonal influenza candidate vaccine. Rationale: The purpose of this study was to evaluate the priming effect of FLU D-QIV vaccine by assessing the immune response after 1 dose of FLU D-QIV in children who were unprimed and in children who had received 2 doses of FLU D-QIV the year before in the primary study [115345 (FLU D-QIV-004 PRI)]. Subjects who received 2-dose FLU D-QIV vaccination in primary study 115345 were considered as primed and received a revaccination dose of the FLU D-QIV vaccine at Day 0 in this study (116023). Subjects who received 2 doses of non-influenza comparator vaccine(s) in primary study 115345 were considered as unprimed and received a primary course of 2 doses of the FLU D-QIV vaccine in this study (116023) at Days 0 and 28. Phase: III Study Period: 06 October 2012 to 05 June 2013 Study Design: Open-label, multi-centre, multi-country study with 2 parallel groups (1:1) Centres: 33 centres (8 centres in Czech Republic, 3 centres in Poland, 12 centres in Spain, 10 centres in United Kingdom) Indication: Immunization against influenza A and B in children aged 17 to 48 months Treatment: The study groups were as follows: FLU D-QIV-1: Subjects in this group were previously primed with 2 doses of FLU D-QIV vaccine in the primary study 115345 and received 1 dose of FLU D-QIV at Day 0 in the current study. FLU D-QIV-2: Subjects in this group were unprimed with respect to FLU D-QIV in the primary study 115345 and received 2 doses of FLU D-QIV at Days 0 and 28 in the current study. The vaccine was administered intramuscularly in the deltoid region of the arm. Objectives: To assess the immune response in terms of haemagglutination inhibition (HI) antibody titre at Day 7 after one dose of FLU D- QIV vaccine (2012-2013 formulation) in vaccine-primed and vaccine-unprimed subjects, for all strains included in the vaccine. Primary Outcome/Efficacy Variable: Serum HI antibody titres at Days 0 and 7 against each of the four vaccine strains after one dose of FLU D-QIV. Derived variables: ‒ Seropositivity rates at Days 0 and 7. ‒ Geometric Mean Titres (GMTs) of HI antibody titres at Days 0 and 7. ‒ Seroconversion rate (SCR)* at Day 7. ‒ Mean Geometric Increase (MGI)** at Day 7. ‒ Seroprotection rate (SPR)*** at Days 0 and 7. *SCR was defined as the percentage of vaccinees that had either a pre-vaccination titre <1:10 and a post-vaccination titre 1:40 or a pre-vaccination titre 1:10 and at least a four-fold increase in post-vaccination titre. **MGI was defined as the geometric mean of the within subject ratios of the post-vaccination reciprocal HI titre to the Day 0 reciprocal HI titre. ***SPR was defined as the percentage of vaccinees with a serum HI titre 1:40 that usually is accepted as indicating protection in adults. Secondary Outcome/Efficacy Variable(s): Immunogenicity: Serum HI antibody titres at Days 0 and 7 against each of the four vaccine strains after one dose of FLU D-QIV. Derived variables: ‒ GMT ratios of primed versus unprimed subjects at Day 7. ‒ SCR difference between primed and unprimed subjects at Day 7. ‒ SPR difference between primed and unprimed subjects at Day 7. ‒ Percentage of subjects with HI antibody titres < 1:10, 1:10 to < 1:40 and ≥ 1:40 at Days 0 and 7. Immunogenicity in the Micro-neutralising/Anti-neuraminidase (MN/AN $ ) subset* of subjects: Serum neutralising antibody titres and anti-neuraminidase antibody titres at Days 0 and 7 against each of the four vaccine strains. Derived variable: ‒ GMTs at Days 0 and 7. ‒ Vaccine Response Rates (VRRs)** at Day 7. ‒ MGIs*** at Day 7.
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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.
GSK Medicine: Fluarix Quadrivalent (GSK2321138A)
Study Number: 116023 (FLU D-QIV-009 EXT 004)
Title: Immunogenicity, safety and reactogenicity study of GSK Biologicals’ quadrivalent seasonal influenza candidate vaccine GSK2321138A, administered to children who previously participated in study 115345. GSK2321138A (FLU D-QIV): GlaxoSmithKline (GSK) Biologicals’ quadrivalent seasonal influenza candidate vaccine.
Rationale: The purpose of this study was to evaluate the priming effect of FLU D-QIV vaccine by assessing the immune response after 1 dose of FLU D-QIV in children who were unprimed and in children who had received 2 doses of FLU D-QIV the year before in the primary study [115345 (FLU D-QIV-004 PRI)]. Subjects who received 2-dose FLU D-QIV vaccination in primary study 115345 were considered as primed and received a revaccination dose of the FLU D-QIV vaccine at Day 0 in this study (116023). Subjects who received 2 doses of non-influenza comparator vaccine(s) in primary study 115345 were considered as unprimed and received a primary course of 2 doses of the FLU D-QIV vaccine in this study (116023) at Days 0 and 28.
Phase: III
Study Period: 06 October 2012 to 05 June 2013
Study Design: Open-label, multi-centre, multi-country study with 2 parallel groups (1:1)
Centres: 33 centres (8 centres in Czech Republic, 3 centres in Poland, 12 centres in Spain, 10 centres in United Kingdom)
Indication: Immunization against influenza A and B in children aged 17 to 48 months
Treatment: The study groups were as follows:
FLU D-QIV-1: Subjects in this group were previously primed with 2 doses of FLU D-QIV vaccine in the primary study 115345 and received 1 dose of FLU D-QIV at Day 0 in the current study.
FLU D-QIV-2: Subjects in this group were unprimed with respect to FLU D-QIV in the primary study 115345 and received 2 doses of FLU D-QIV at Days 0 and 28 in the current study.
The vaccine was administered intramuscularly in the deltoid region of the arm.
Objectives: To assess the immune response in terms of haemagglutination inhibition (HI) antibody titre at Day 7 after one dose of FLU D-QIV vaccine (2012-2013 formulation) in vaccine-primed and vaccine-unprimed subjects, for all strains included in the vaccine.
Primary Outcome/Efficacy Variable:
Serum HI antibody titres at Days 0 and 7 against each of the four vaccine strains after one dose of FLU D-QIV. Derived variables:
‒ Seropositivity rates at Days 0 and 7. ‒ Geometric Mean Titres (GMTs) of HI antibody titres at Days 0 and 7. ‒ Seroconversion rate (SCR)* at Day 7. ‒ Mean Geometric Increase (MGI)** at Day 7. ‒ Seroprotection rate (SPR)*** at Days 0 and 7.
*SCR was defined as the percentage of vaccinees that had either a pre-vaccination titre <1:10 and a post-vaccination titre
1:40 or a pre-vaccination titre 1:10 and at least a four-fold increase in post-vaccination titre. **MGI was defined as the geometric mean of the within subject ratios of the post-vaccination reciprocal HI titre to the Day 0 reciprocal HI titre.
***SPR was defined as the percentage of vaccinees with a serum HI titre 1:40 that usually is accepted as indicating protection in adults.
Serum HI antibody titres at Days 0 and 7 against each of the four vaccine strains after one dose of FLU D-QIV. Derived variables:
‒ GMT ratios of primed versus unprimed subjects at Day 7. ‒ SCR difference between primed and unprimed subjects at Day 7. ‒ SPR difference between primed and unprimed subjects at Day 7. ‒ Percentage of subjects with HI antibody titres < 1:10, 1:10 to < 1:40 and ≥ 1:40 at Days 0 and 7.
Immunogenicity in the Micro-neutralising/Anti-neuraminidase (MN/AN$) subset* of subjects:
Serum neutralising antibody titres and anti-neuraminidase antibody titres at Days 0 and 7 against each of the four vaccine strains.
Derived variable: ‒ GMTs at Days 0 and 7. ‒ Vaccine Response Rates (VRRs)** at Day 7. ‒ MGIs*** at Day 7.
* The MN/AN subset included 226 subjects in total, approximately 56 in each age stratum (17 to 29 months old and 30 to 48 months old) of each study group (FLU D-QIV-1 and FLU D-QIV-2 groups). $Neuraminidase inhibitor antibodies For neutralising antibodies: ** VRR was defined as the percentage of vaccinees who had either a pre-vaccination titre <cut-off and a post-vaccination titre ≥ 4-fold of half of the cut-off or a pre-vaccination titre ≥cut-off and at least a 4-fold increase in post-vaccination titres. *** MGI was defined as the fold increase in GMTs post-vaccination compared to Day 0. Safety:
Occurrence of each solicited local Adverse Event (AE): ‒ Percentage, duration and intensity during the 7-day follow-up period (i.e. day of vaccination and 6 subsequent days)
after the first vaccination.
Occurrence of each solicited general AE: ‒ Percentage, duration, intensity and relationship to vaccination during the 7-day follow-up period (i.e. day of
vaccination and 6 subsequent days) after the first vaccination.
Occurrence of unsolicited AEs: ‒ Percentage, intensity and relationship to vaccination during the 28-day follow up period (i.e. day of vaccination and
27 subsequent days) after the first vaccination.
Occurrence of AEs with Medically Attended Visit (MAV): ‒ Percentage, intensity and relationship to vaccination of AEs with MAV during the entire study period.
Occurrence of Serious Adverse Events (SAEs) and Potential Immune-Mediated Diseases (pIMDs): ‒ Percentage and relationship to vaccination of SAEs and pIMDs during the entire study period.
Statistical Methods: Analyses were performed on the Total Vaccinated cohort, the According-to-Protocol (ATP) cohort for immunogenicity and ATP cohort for immunogenicity (ATP-I) excluding subjects who had an RT-PCR confirmed influenza infection in study 115345.
The Total Vaccinated cohort included all subjects with at least one vaccine administration documented.
The ATP cohort for immunogenicity included all evaluable subjects (i.e., those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria) who received the study vaccine according to their treatment assignment, for whom the assay results for antibodies against at least one study vaccine strain after vaccination and for whom data concerning immunogenicity outcome measures were available.
The ATP-I excluding subjects who had an RT-PCR confirmed influenza infection in study 115345 consisted of all evaluable subjects from the ATP-I, excluding subjects who had an RT-PCR confirmed influenza infection in study 115345. These subjects were identified as having an influenza episode [per Flu D-QIV-004 (115345) protocol definition] which occurred during the influenza surveillance period, had nasal swab taken within 7 days of the start of the influenza episode, and confirmed by RT-PCR.
Analysis of Immunogenicity The analysis was performed on the ATP cohort for immunogenicity and the ATP-I excluding subjects with a RT-PCR-confirmed influenza infection in study 115345. For the humoral response in terms of HI antibodies for all vaccine strains, the following parameters were calculated with 95% confidence interval (CI), by group for all subjects:
Seropositivity rates at Days 0 and 7.
GMTs at Days 0 and 7.
SCR at Day 7.
SPR at Days 0 and 7.
MGI at Day 7.
Percentage of subjects with HI antibody titres <1:10, 1:10 - <1:40 and ≥ 1:40 at Days 0 and 7. Additionally, the percentage of subjects with HI antibody titres ≥1:60 and ≥1:80 at Days 0 and 7 were also calculated with 95% confidence interval (CI), by group for all subjects on ATP-I excluding subjects with a RT-PCR-confirmed influenza infection in study 115345. For the humoral response in terms of neutralising and anti-neuraminidase antibodies for all vaccine strains, the following parameters were calculated with 95% CI, by group and by each age stratum for a subset of subjects:
GMTs at Days 0 and 7.
VRR at Day 7.
MGI at Day 7. For the humoral response in terms of HI antibodies for all vaccine strains, the following parameters were calculated with 95% CI between FLU D-QIV-1 and FLU D-QIV-2 groups for all subjects at Day 7:
GMT ratio.
SCR difference.
SPR difference. Analysis of Safety The analysis was performed on the Total Vaccinated cohort. The percentages of subjects reporting each individual solicited local and general symptom during the 7 day (Days 0 –6) follow-up period after first vaccination were tabulated with exact 95% CI. The same tabulation was performed for grade 3 solicited symptoms and for general symptoms assessed by the investigator as causally related to the study vaccination. The duration of solicited local/general symptoms during the 7 day (days 0-6) follow up period after first vaccination were also tabulated. The percentages of subjects with at least one report of an unsolicited AE classified by Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term during the 28-day (Days 0-27) follow-up period after first vaccination were tabulated. The same tabulation was performed for grade 3 unsolicited AEs and for unsolicited AEs assessed by the investigator to be causally related to vaccination. The percentage of subjects reporting AE with MAVs during the entire study period were tabulated and classified according to MedDRA Preferred Term. The same tabulation was performed for grade 3 AE with MAVs and for AE with MAVs assessed by the investigator to be causally related to vaccination. The percentage of subjects reporting SAEs and pIMDs (including related pIMDs) during the entire study period were summarized and classified according to MedDRA Preferred Term. Fatal SAEs and SAEs assessed by the investigators to be causally related to vaccination were also reported
Study Population: Healthy male and female children aged 17 to 48 months who received a 2-dose vaccination in the primary study 115345. Written informed consent was obtained from the parent(s)/LAR(s) of the subject.
Number of Subjects: FLU D-QIV-1 Group FLU D-QIV-2 Group
Planned, N 226 226
Enrolled, N (Total Vaccinated cohort) 241 229
Completed, n (%) 238 (98.8) 221 (96.5)
Total Number Subjects Withdrawn, n (%) 3 (1.2) 8 (3.5)
Withdrawn due to Adverse Events, n (%) 0 (0.0) 0 (0.0)
Withdrawn due to Lack of Efficacy, n (%) Not Applicable Not Applicable
Withdrawn for other reasons, n (%) 3 (1.2) 8 (3.5)
Demographics FLU D-QIV-1 Group FLU D-QIV-2 Group
N (Total Vaccinated cohort) 241 229
Sex, n (%) Females
114 (47.3) 96 (41.9)
Males 127 (52.7) 133 (58.1)
Mean Age, years (SD) 33.2 (7.54) 32.5 (7.39)
Median 32.0 31.0
Minimum, Maximum 18,47 17, 47
White Caucasian, n (%) 236 (97.9) 224 (97.8)
Primary Outcome Results: Seropositivity rates and GMTs for HI antibodies titres at Day 0 and Day 7 post vaccination Dose 1 (ATP cohort for immunogenicity)
≥ 1:10 GMT
95% CI 95% CI
HI Antibody Group Timing N n % LL UL Value LL UL A/Christchurch/16/2010 (H1N1) FLU D-QIV-1 PRE 221 189 85.5 80.2 89.9 43.1 33.8 54.9
GMT = geometric mean antibody titre calculated on all subjects N = number of subjects with available results n/% = number/percentage of subjects with titre equal to or above specified value 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE = Pre-vaccination at Day 0, PI(D7) = Post-vaccination Dose 1 at Day 7
Primary Outcome Results: Seropositivity rates, SPR and GMTs for HI antibodies titres at Day 0 and Day 7 post vaccination Dose 1 (ATP-I excluding subjects who had an RT-PCR confirmed influenza infection in study 115345)
≥ 1:10 ≥ 1:40 GMT
95% CI 95% CI 95% CI
HI Antibody Group Timing N n % LL UL n % LL UL value LL UL
GMT = geometric mean antibody titre calculated on all subjects N = number of subjects with available results n/% = number/percentage of subjects with titre equal to or above specified value 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE = Pre-vaccination at Day 0, PI(D7) = Post-vaccination Dose 1 at Day 7
Primary Outcome Results: SCR for HI antibodies titres at Day 7 post vaccination Dose 1 (ATP cohort for immunogenicity) SCR
Seroconversion defined as: For initially seronegative subjects, antibody titre ≥ 1:40 after vaccination For initially seropositive subjects, antibody titre after vaccination ≥ 4 fold the pre-vaccination antibody titre N = Number of subjects with pre- and post-vaccination results available n/% = number/percentage of seroconverted subjects 95% CI = 95% confidence interval, LL = Lower Limit, UL = Upper Limit
Primary Outcome Results: SCR for HI antibodies titres at day 7 post vaccination Dose 1 (ATP-I excluding subjects who had an RT-PCR confirmed influenza infection in study 115345)
Seronegative subjects=antibody titre < 1:10 prior to vaccination Seropositive subjects=antibody titre ≥ 1:10 prior to vaccination SCR defined as: For initially seronegative subjects, antibody titre ≥ 1:40 at post-vaccination For initially seropositive subjects, antibody titre at post-vaccination ≥ 4 fold the pre-vaccination antibody titre N = Number of subjects with both pre- and post-vaccination results available n/% = Number/percentage of seroconverted subjects 95% CI = 95% confidence interval, LL = Lower Limit, UL = Upper Limit
Primary Outcome Results: MGI for HI antibodies titres at Day 7 post vaccination Dose 1 (ATP cohort for immunogenicity)
MGI = Mean Geometric increase in serum HI GMTs post-vaccination N = Number of subjects with pre- and post-vaccination results available 95% CI = 95% confidence interval, LL = Lower Limit, UL = Upper Limit
Primary Outcome Results: MGI for HI antibodies titres at day 7 post vaccination Dose 1 (ATP-I excluding subjects who had an RT-PCR confirmed influenza infection in study 115345)
MGI
95% CI
HI Antibody Group N Value LL UL A/Christchurch/16/2010 (H1N1) FLU D-QIV-1 210 10.0 8.1 12.2
SPR = Seroprotection rate N = Number of subjects with available results n/% = number/percentage of subjects with HI titre ≥ 1:40 95% CI = 95% confidence interval, LL = Lower Limit, UL = Upper Limit PRE = Pre-vaccination at Day 0 PI(D7) = Post-vaccination Dose 1 at Day 7 Secondary Outcome Results: GMT ratios of HI antibodies titres at Day 7 post vaccination Dose 1 (ATP cohort for immunogenicity)
Adjusted GMT ratio (FLU D-QIV-1 / FLU D-QIV-2)
FLU D-QIV-1 FLU D-QIV-2 95% CI
HI Antibody N Adjusted GMT N Adjusted GMT Value LL UL
Adjusted GMT = geometric mean antibody titre adjusted for Age (Months) N = Number of subjects with both pre- and post-vaccination results available 95% CI = 95% confidence interval for the adjusted GMT ratio (ANCOVA model: adjustment for Age (Months)-pooled variance; LL = lower limit, UL = upper limit
Secondary Outcome Results: GMT ratios of HI antibodies titres at Day 7 post vaccination Dose 1 (ATP-I excluding subjects who had an RT-PCR confirmed influenza infection in study 115345)
Adjusted GMT ratio (FLU D-QIV-1 / FLU D-QIV-2)
FLU D-QIV-1 FLU D-QIV-2 95% CI
HI Antibody N Adjusted GMT N Adjusted GMT Value LL UL
Adjusted GMT = geometric mean antibody titre adjusted for Age (Months) N = Number of subjects with both pre- and post-vaccination results available 95% CI = 95% confidence interval for the adjusted GMT ratio (Ancova model: adjustment for Age (Months) - pooled variance); LL = lower limit, UL = upper limit
Secondary Outcome Results: Difference in SCR for HI antibodies at Day 7 post vaccination Dose 1 (ATP cohort for immunogenicity)
Difference in SCR (FLU D-QIV-1 minus FLU D-QIV-2)
FLU D-QIV-1 FLU D-QIV-2 95% CI HI Antibody N n % N n % % LL UL A/Christchurch/16/2010 (H1N1) 221 170 76.9 202 65 32.2 44.74 35.87 52.84
SCR defined as: For initially seronegative subjects: post-vaccination antibody titre ≥ 1:40 at PI(D7) For initially seropositive subjects: antibody titre at PI(D7) ≥ 4 fold the pre-vaccination antibody titre N = number of subjects with pre- and post-vaccination results available n/% = number/percentage of subjects with a vaccine response 95% CI = Standardized asymptotic 95% confidence interval; LL = lower limit, UL = upper limit
Secondary Outcome Results: Difference in SCR for HI antibodies at Day 7 post vaccination Dose 1 (ATP-I excluding subjects who had an RT-PCR confirmed influenza infection in study 115345)
Difference in SCR (FLU D-QIV-1 minus FLU D-QIV-2)
FLU D-QIV-1 FLU D-QIV-2 95% CI HI Antibody N n % N n % % LL UL
Seroconversion defined as : For initially seronegative subjects: post-vaccination antibody titre ≥ 1:40 at PI(D7) For initially seropositive subjects : antibody titre at PI(D7) ≥ 4 fold the pre-vaccination antibody titre N = number of subjects with pre- and post-vaccination results available n/% = number/percentage of seroprotected subjects 95% CI = Standardized asymptotic 95% confidence interval; LL = lower limit, UL = upper limit
Secondary Outcome Results: Difference in SPR for HI antibodies at Day 7 post vaccination Dose 1 (ATP cohort for immunogenicity)
Difference in SPR (FLU D-QIV-1 minus FLU D-QIV-2)
FLU D-QIV-1 FLU D-QIV-2 95% CI HI Antibody N % N % % LL UL
N = number of subjects with available results % = percentage of subjects for each strain, HI titre ≥ 1:40 95% CI = 95% Standardized asymptotic confidence interval; LL = lower limit, UL = upper limit
Secondary Outcome Results: Difference in SPR for HI antibodies at Day 7 post vaccination Dose 1 (ATP-I excluding subjects who had an RT-PCR confirmed influenza infection in study 115345)
Difference in SPR (FLU D-QIV-1 minus FLU D-QIV-2)
FLU D-QIV-1 FLU D-QIV-2 95% CI HI Antibody Type N n % N n % % LL UL
N = number of subjects with available results n/% = number/percentage of subjects with HI titre ≥ 1:40 95% CI = Standardized asymptotic 95% confidence interval; LL = lower limit, UL = upper limit
Secondary Outcome Results: Number (%) of subjects with HI antibody titres <1:10, 1:10 to <1:40 and ≥1:40 at Day 0 and Day 7 post vaccination Dose 1 (ATP cohort for immunogenicity)
N = number of subjects with available results n/% = number/percentage of subjects with titre within the specified range PRE = Pre-vaccination at Day 0, P1 (D7) = Post-vaccination Dose 1 at Day 7
Secondary Outcome Results: Number (%) of subjects with HI antibody titres <1:10, 1:10 to <1:40, ≥1:40, ≥1:60 and ≥1:80 at Day 0 and Day 7 post vaccination Dose 1 (ATP-I excluding subjects who had an RT-PCR confirmed influenza infection in study 115345)
<1:10 ≥1:10 ≥1:40 ≥1:60 ≥1:80 HI Antibody Group Timing N n % n % n % n % n %
N = number of subjects with available results n/% = number/percentage of subjects with titre within the specified range PRE = Pre-vaccination at Day 0, PI(D7) = Post-vaccination Dose 1 at Day 7
Secondary Outcome Results: Seropositivity rates and GMTs for neutralizing antibodies titres (H1N1 - H3N2 - Victoria) at Day 0 and Day 7 post vaccination Dose 1 (ATP cohort for immunogenicity)
17-29M = 17-29 months old subjects 30-48M = 30-48 months old subjects GMT = geometric mean antibody titre calculated on all subjects N = number of subjects with available results n/% = number/percentage of subjects with titre equal to or above specified value 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE = Pre-vaccination at Day 0 PI(D7) = Post-vaccination Dose 1 at Day 7
Secondary Outcome Results: Seropositivity rates and GMTs for neutralising antibodies titres (H1N1 - H3N2 - Victoria) at Day 0 and Day 7 post vaccination Dose 1 (ATP-I excluding subjects who had an RT-PCR confirmed influenza infection in study 115345)
GMT = geometric mean antibody titre calculated on all subjects N = number of subjects with available results n/% = number/percentage of subjects with titre within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE = Pre-vaccination at Day 0, P1 (D7) = Post-vaccination Dose 1 at Day 7
Secondary Outcome Results: Seropositivity rates and GMTs for neutralising antibodies titres (H1N1 - H3N2 - Victoria) at Day 0 and Day 7 post Dose 1 - by age strata (ATP cohort for immunogenicity)
GMT = geometric mean antibody titre calculated on all subjects N = number of subjects with available results n/% = number/percentage of subjects with titre within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE = Pre-vaccination at Day 0, PI(D7) = Post-vaccination Dose 1 at Day 7
Secondary Outcome Results: Seropositivity rates and GMTs for neutralizing antibodies titres (Yamagata) at Day 0 and Day 7 post vaccination Dose 1 (ATP cohort for immunogenicity)
GMT = geometric mean antibody titre calculated on all subjects N = number of subjects with available results n/% = number/percentage of subjects with titre within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE = Pre-vaccination at Day 0, P1 (D7) = Post-vaccination Dose 1 at Day 7 Secondary Outcome Results: Seropositivity rates and GMTs for neutralising antibodies titres (Yamagata) at Day 0 and Day 7 post Dose 1 - by age strata (ATP cohort for immunogenicity)
≥ 1:57 GMT
95% CI 95% CI
MN Antibody Group Sub-group Timing N n % LL UL value LL UL B/Hubei- Wujiagang/158/2009) (Yamagata)
17-29M = 17-29 months old subjects 30-48M = 30-48 months old subjects GMT = geometric mean antibody titre calculated on all subjects N = number of subjects with available results n/% = number/percentage of subjects with titre equal to or above specified value 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE = Pre-vaccination at Day 0 PI(D7) = Post-vaccination Dose 1 at Day 7
Secondary Outcome Results: Seropositivity rates and GMTs for neutralising antibodies titres (Yamagata) at Day 0 and Day 7 post vaccination Dose 1 (ATP-I excluding subjects who had an RT-PCR confirmed influenza infection in study 115345)
≥ 1:57 GMT
95% CI 95% CI
MN Antibody Group Timing N n % LL UL value LL UL B/Hubei-Wujiagang/158/2009 (Yamagata)
GMT = geometric mean antibody titre calculated on all subjects N = number of subjects with available results n/% = number/percentage of subjects with titre within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE = Pre-vaccination at Day 0, PI(D7) = Post-vaccination Dose 1 at Day 7
Secondary Outcome Results: VRR for neutralising antibody titres at Day 7 post vaccination Dose 1 (ATP cohort for immunogenicity)
Vaccine response for A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2) and B/Brisbane/60/2008 (Victoria) neutralizing antibody was defined as: For initially seronegative subjects, antibody titre ≥ 1:56 after vaccination and For initially seropositive subjects, antibody titre after vaccination ≥ 4 fold the pre-vaccination antibody titre N = Number of subjects with pre- and post-vaccination results available n/% = number/percentage of seroconverted subjects 95% CI = 95% confidence interval, LL = Lower Limit, UL = Upper Limit
Secondary Outcome Results: VRR for neutralising antibodies titres (H1N1 - H3N2 - Victoria) at day 7 post vaccination Dose 1 - by age strata (ATP cohort for immunogenicity)
17-29M = 17-29 months old subjects 30-48M = 30-48 months old subjects Vaccine response defined as: For initially seronegative subjects, antibody titre ≥ 1:56 after vaccination For initially seropositive subjects, antibody titre after vaccination ≥ 4 fold the pre-vaccination antibody titre N = Number of subjects with pre- and post-vaccination results available n/% = Number/percentage of seroconverted subjects 95% CI = 95% confidence interval, LL = Lower Limit, UL = Upper Limit
Secondary Outcome Results: VRR for neutralising antibodies titres at day 7 post vaccination Dose 1 (ATP-I excluding subjects who had an RT-PCR confirmed influenza infection in study 115345)
Vaccine response for A/Christchurch/16/2010 (H1N1), A/Victoria/361/2011 (H3N2) and B/Brisbane/60/2008 (Victoria) was defined as: For initially seronegative subjects, antibody titre ≥ 1:56 after vaccination For initially seropositive subjects, antibody titre after vaccination ≥ 4 fold the pre-vaccination antibody titre N = Number of subjects with pre- and post-vaccination results available n/% = Number/percentage of seroconverted subjects 95% CI = 95% confidence interval, LL = Lower Limit, UL = Upper Limit
Secondary Outcome Results: VRR for neutralising antibody titres (Yamagata) at Day 7 post vaccination Dose 1 (ATP cohort for immunogenicity) Vaccine response
Vaccine response for B/Hubei-Wujiagang/158/2009 (Yamagata) neutralizing antibody was defined as: For initially seronegative subjects, antibody titre ≥ 1:114 after vaccination; For initially seropositive subjects, antibody titre after vaccination ≥ 4 fold the pre-vaccination antibody titre N = Number of subjects with pre- and post-vaccination results available n/% = number/percentage of seroconverted subjects 95% CI = 95% confidence interval, LL = Lower Limit, UL = Upper Limit
Secondary Outcome Results: VRR for neutralising antibodies titres (Yamagata) at day 7 post Dose 1 - by age strata (ATP cohort for immunogenicity)
Vaccine response
95% CI
MN Antibody Group Sub-group N n % LL UL
B/Hubei-Wujiagang/158/2009 (Yamagata)
FLU D-QIV-1 17-29M 53 17 32.1 19.9 46.3
30-48M 54 28 51.9 37.8 65.7
FLU D-QIV-2 17-29M 51 6 11.8 4.4 23.9
30-48M 54 9 16.7 7.9 29.3
17-29M = 17-29 months old subjects 30-48M = 30-48 months old subjects Vaccine response defined as: For initially seronegative subjects, antibody titre ≥ 1:114 after vaccination For initially seropositive subjects, antibody titre after vaccination ≥ 4 fold the pre-vaccination antibody titre N = Number of subjects with pre- and post-vaccination results available n/% = Number/percentage of seroconverted subjects 95% CI = 95% confidence interval, LL = Lower Limit, UL = Upper Limit
Secondary Outcome Results: VRR for neutralising antibodies titres (Yamagata) at day 7 post Dose 1 (ATP-I excluding subjects who had an RT-PCR confirmed influenza infection in study 115345)
Vaccine response
95% CI
MN Antibody Group N n % LL UL B/Hubei-Wujiagang/158/2009 (Yamagata) FLU D-QIV-1 100 42 42.0 32.2 52.3
FLU D-QIV-2 86 11 12.8 6.6 21.7
Vaccine response for B/Hubei-Wujiagang/158/2009 (Yamagata) neutralizing antibody was defined as: For initially seronegative subjects, antibody titre ≥ 1:114 after vaccination For initially seropositive subjects, antibody titre after vaccination ≥ 4 fold the pre-vaccination antibody titre N = Number of subjects with pre- and post-vaccination results available n/% = Number/percentage of seroconverted subjects 95% CI = 95% confidence interval, LL = Lower Limit, UL = Upper Limit
Secondary Outcome Results: MGI for neutralising antibodies titres at Day 7 post vaccination Dose 1 (ATP cohort for immunogenicity)
MGI
95% CI
MN Antibody Group N Value LL UL A/Christchurch/16/2010 (H1N1) FLU D-QIV-1 97 10.6 8.2 13.7
MGI = Mean Geometric increase in serum MN GMTs post-vaccination N = Number of subjects with pre- and post-vaccination results available 95% CI = 95% confidence interval, LL = Lower Limit, UL = Upper Limit
Secondary Outcome Results: MGI for neutralising antibodies titres at Day 7 post vaccination Dose 1 - by age strata (ATP cohort for immunogenicity)
17-29M = 17-29 months old subjects 30-48M = 30-48 months old subjects N = Number of subjects with pre- and post-vaccination results available MGI = Mean Geometric increase in serum neutralising GMTs post-vaccination 95% CI = 95% confidence interval, LL = Lower Limit, UL = Upper Limit
Secondary Outcome Results: MGI for neutralising antibodies titres at day 7 post vaccination Dose 1 (ATP-I excluding subjects who had an RT-PCR confirmed influenza infection in study 115345)
MGI = Mean Geometric increase in serum MN GMTs post-vaccination N = Number of subjects with pre- and post-vaccination results available
95% CI = 95% confidence interval, LL = Lower Limit, UL = Upper Limit Secondary Outcome Results: Seropositivity rates and GMTs for anti-neuraminidase antibodies titres (H1N1 - Victoria - Yamagata) at Day 0 and Day 7 post vaccination Dose 1 (ATP cohort for immunogenicity)
GMT = geometric mean antibody titre calculated on all subjects N = number of subjects with available results n/% = number/percentage of subjects with titre within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE = Pre-vaccination at Day 0, P1 (D7) = Post-vaccination Dose 1 at Day 7
Secondary Outcome Results: Seropositivity rates and GMTs for Anti-neuraminidase antibodies titres (H1N1 - Victoria - Yamagata) at Day 0 and Day 7 post vaccination Dose 1 - by age strata (ATP cohort for immunogenicity)
≥ 1:20 GMT
95% CI 95% CI
NI Antibody Group Sub-group Timing N n % LL UL value LL UL
17-29M = 17-29 months old subjects 30-48M = 30-48 months old subjects GMT = geometric mean antibody titre calculated on all subjects N = number of subjects with available results n/% = number/percentage of subjects with titre equal to or above specified value 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE = Pre-vaccination at Day 0 PI(D7) = Post-vaccination Dose 1 at Day 7
Secondary Outcome Results: Seropositivity rates and GMTs for anti-neuraminidase antibodies titres (H1N1 - Victoria - Yamagata) at Day 0 and Day 7 post vaccination Dose 1 (ATP-I excluding subjects who had an RT-PCR confirmed influenza infection in study 115345)
GMT = geometric mean antibody titre calculated on all subjects N = number of subjects with available results n/% = number/percentage of subjects with titre within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE = Pre-vaccination at Day 0, PI(D7) = Post-vaccination Dose 1 at Day 7 Secondary Outcome Results: Seropositivity rates and GMTs for anti-neuraminidase antibodies titres (H3N2) at Day 0 and Day 7 post vaccination Dose 1 (ATP cohort for immunogenicity)
≥ 1:40 GMT
95% CI 95% CI
NI Antibody Group Timing N n % LL UL Value LL UL
A/Victoria/361/2011 (H3N2)
FLU D-QIV-1
PRE 107 68 63.6 53.7 72.6 38.4 33.7 43.7
PI(D7) 107 104 97.2 92.0 99.4 189.4 155.9 230.2
FLU D-QIV-2
PRE 106 58 54.7 44.8 64.4 58.8 47.2 73.4
PI(D7) 109 71 65.1 55.4 74.0 114.2 84.1 155.2
GMT = geometric mean antibody titre calculated on all subjects N = number of subjects with available results n/% = number/percentage of subjects with titre within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE = Pre-vaccination at Day 0, P1 (D7) = Post-vaccination Dose 1 at Day 7 Secondary Outcome Results: Seropositivity rates and GMTs for Anti-neuraminidase antibodies titres (H3N2) at Day 0 and Day 7 post vaccination Dose 1 - by age strata (ATP cohort for immunogenicity)
≥ 1:40 GMT
95% CI 95% CI NI Antibody Group Sub-group Timing N n % LL UL value LL UL
17-29M = 17-29 months old subjects 30-48M = 30-48 months old subjects GMT = geometric mean antibody titre calculated on all subjects N = number of subjects with available results n/% = number/percentage of subjects with titre equal to or above specified value 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE = Pre-vaccination at Day 0 PI(D7) = Post-vaccination Dose 1 at Day 7
Secondary Outcome Results: Seropositivity rates and GMTs for anti-neuraminidase antibodies titres (H3N2) at Day 0 and Day 7 post vaccination Dose 1 (ATP-I excluding subjects who had an RT-PCR confirmed influenza infection in study 115345)
GMT = geometric mean antibody titre calculated on all subjects N = number of subjects with available results n/% = number/percentage of subjects with titre within the specified range 95% CI = 95% confidence interval; LL = Lower Limit, UL = Upper Limit PRE = Pre-vaccination at Day 0, PI(D7) = Post-vaccination Dose 1 at Day 7
Secondary Outcome Results: VRR for anti-neuraminidase antibody titres (H1N1 - Victoria - Yamagata) at Day 7 post vaccination Dose 1 (ATP cohort for immunogenicity)
Vaccine response for A/Christchurch/16/2010 (H1N1), B/Brisbane/60/2008 (Victoria), B/Hubei-Wujiagang/158/2009 (Yamagata) anti-neuraminidase was defined as: For initially seronegative subjects, antibody titre ≥ 1:40 after vaccination; For initially seropositive subjects, antibody titre after vaccination ≥ 4 fold the pre-vaccination antibody titre N = Number of subjects with pre- and post-vaccination results available n/% = Number/percentage of seroconverted subjects 95% CI = 95% confidence interval, LL = Lower Limit, UL = Upper Limit
Secondary Outcome Results: VRR for Anti-neuraminidase antibodies titres (H1N1 - Victoria - Yamagata) at day 7 post vaccination Dose 1 - by age strata (ATP cohort for immunogenicity)
17-29M = 17-29 months old subjects 30-48M = 30-48 months old subjects Vaccine response defined as: For initially seronegative subjects, antibody titre ≥ 1:40 after vaccination For initially seropositive subjects, antibody titre after vaccination ≥ 4 fold the pre-vaccination antibody titre N = Number of subjects with pre- and post-vaccination results available n/% = Number/percentage of seroconverted subjects 95% CI = 95% confidence interval, LL = Lower Limit, UL = Upper Limit
Secondary Outcome Results: VRR for anti-neuraminidase antibodies titres (H1N1 - Victoria - Yamagata) at day 7 post vaccination Dose 1 (ATP-I excluding subjects who had an RT-PCR confirmed influenza infection in study 115345)
Vaccine response for A/Christchurch/16/2010 (H1N1), B/Brisbane/60/2008 (Victoria), B/Hubei-Wujiagang/158/2009 (Yamagata) anti-neuraminidase was defined as: For initially seronegative subjects, antibody titre ≥ 1:40 after vaccination For initially seropositive subjects, antibody titre after vaccination ≥ 4 fold the pre-vaccination antibody titre N = Number of subjects with pre- and post-vaccination results available n/% = Number/percentage of seroconverted subjects 95% CI = 95% confidence interval, LL = Lower Limit, UL = Upper Limit
Secondary Outcome Results: VRR for anti-neuraminidase antibody titres (H3N2) at Day 7 post vaccination Dose 1 (ATP cohort for immunogenicity)
Vaccine response for A/Victoria/361/2011 (H3N2) anti-neuraminidase is defined as: For initially seronegative subjects, antibody titre ≥1: 80 after vaccination; For initially seropositive subjects, antibody titre after vaccination ≥ 4 fold the pre-vaccination antibody titre N = Number of subjects with pre- and post-vaccination results available n/% = Number/percentage of seroconverted subjects 95% CI = 95% confidence interval, LL = Lower Limit, UL = Upper Limit
Secondary Outcome Results: VRR for Anti-neuraminidase antibodies titres (H3N2) at day 7 post vaccination Dose 1 - by age strata (ATP cohort for immunogenicity)
17-29M = 17-29 months old subjects 30-48M = 30-48 months old subjects Vaccine response defined as: For initially seronegative subjects, antibody titre ≥ 1:80 after vaccination For initially seropositive subjects, antibody titre after vaccination ≥ 4 fold the pre-vaccination antibody titre N = Number of subjects with pre- and post-vaccination results available n/% = Number/percentage of seroconverted subjects 95% CI = 95% confidence interval, LL = Lower Limit, UL = Upper Limit
Secondary Outcome Results: VRR for anti-neuraminidase antibodies titres (H3N2) at day 7 post vaccination Dose 1 (ATP-I excluding subjects who had an RT-PCR confirmed influenza infection in study 115345)
Vaccine response
95% CI
NI Antibody Group N n % LL UL A/Victoria/361/2011 (H3N2) FLU D-QIV-1 100 70 70.0 60.0 78.8
FLU D-QIV-2 86 22 25.6 16.8 36.1
Vaccine response defined as: For initially seronegative subjects, antibody titre ≥ 1:80 after vaccination For initially seropositive subjects, antibody titre after vaccination ≥ 4 fold the pre-vaccination antibody titre N = Number of subjects with pre- and post-vaccination results available n/% = Number/percentage of seroconverted subjects 95% CI = 95% confidence interval, LL = Lower Limit, UL = Upper Limit
Secondary Outcome Results: MGI for anti-neuraminidase antibodies titres at Day 7 post vaccination Dose 1 (ATP cohort for immunogenicity)
MGI
95% CI
NI Antibody Group N Value LL UL A/Christchurch/16/2010 (H1N1) FLU D-QIV-1 105 8.3 6.5 10.7
MGI = Mean Geometric increase in serum NI GMTs post-vaccination N = Number of subjects with pre- and post-vaccination results available 95% CI = 95% confidence interval, LL = Lower Limit, UL = Upper Limit
Secondary Outcome Results: MGI for Anti-neuraminidase antibodies titres at Day 7 post vaccination Dose 1 - by age strata (ATP cohort for immunogenicity)
17-29M = 17-29 months old subjects 30-48M = 30-48 months old subjects N = Number of subjects with pre- and post-vaccination results available MGI = Mean Geometric increase in serum Anti-neuraminidase GMTs post-vaccination 95% CI = 95% confidence interval, LL = Lower Limit, UL = Upper Limit
Secondary Outcome Results: MGI for anti-neuraminidase antibodies titres at Day 7 post vaccination Dose 1 (ATP-I excluding subjects who had an RT-PCR confirmed influenza infection in study 115345)
MGI = Mean Geometric increase in serum NI GMTs post-vaccination N = Number of subjects with pre- and post-vaccination results available
95% CI = 95% confidence interval, LL = Lower Limit, UL = Upper Limit Secondary Outcome Results: Number (%) of subjects reporting solicited local symptoms during the 7-day (Days 0-6) post-dose 1 vaccination period (Total Vaccinated cohort)
FLU D-QIV-1 Group FLU D-QIV-2 Group
95 % CI 95 % CI Symptom Intensity N n % LL UL N n % LL UL
N= number of subjects with the documented dose n/%= number/percentage of subjects reporting at least once the symptom 95%CI = Exact 95% confidence interval; LL = lower limit, UL = upper limit Any = occurrence of any local symptom regardless of their intensity grade Grade 3 pain = Cried when limb was moved/spontaneously painful
Secondary Outcome Results: Number (%) of subjects reporting solicited general symptoms during the 7-day (Days 0-6) post-dose 1 vaccination period (Total Vaccinated cohort)
FLU D-QIV-1 Group FLU D-QIV-2 Group
95 % CI 95 % CI
Symptom Intensity/Relationship N n % LL UL N n % LL UL Drowsiness Any 238 54 22.7 17.5 28.5 224 44 19.6 14.7 25.5
N= number of subjects with the documented dose n/%= number/percentage of subjects reporting the symptom at least once 95%CI= Exact 95% confidence interval; LL = lower limit, UL = upper limit Any = occurrence of any general symptom regardless of their intensity grade or relationship to vaccination Grade 3 irritability/fussiness = crying that could not be comforted/prevented normal activity Grade 3 drowsiness = drowsiness that prevented normal activity Grade 3 loss of appetite = did not eat at all Related = symptom assessed by the investigator as causally related to the vaccination Secondary Outcome Results: Number of days with symptoms during the 7-day (Days 0-6) post-vaccination Dose 1 period (Total Vaccinated cohort)
N = number of subjects with at least one administered dose n/% = number/percentage of subjects reporting the symptom at least once Grade 3 = event that prevented normal activities Related = event assessed by the investigator as causally related to the study vaccination Counting rule applied: As there were more than 30 subjects per treatment group and ≤ 3 groups, only 10 most frequent events in each treatment group were listed. - : Implies that event was not reported in the particular group or that the adverse event was reported in the particular group but did not fall within the pre-defined counting rule of 10 most frequent events for that group.
Secondary Outcome Results: Number (%) of subjects with pIMDs during the entire study period (Total Vaccinated cohort)
All pIMDs
FLU D-QIV-1 Group N = 241
FLU D-QIV-2 Group N = 229
Subjects with any pIMD(s), n (%) 0 (0.0) 0 (0.0) Subjects with related pIMD(s), n (%) 0 (0.0) 0 (0.0)
N = number of subjects with at least one administered dose n/% = number/percentage of subjects reporting the symptom at least once Related = event assessed by the investigator as causally related to the study vaccination
Safety Results: Number (%) of subjects with unsolicited AEs during the 28-day (Days 0-27) follow up period after the first vaccination (Total Vaccinated cohort)
Most Frequent Unsolicited Adverse Events – On-Therapy (Occurring within Days 0 –27 following the first vaccination)
FLU D-QIV-1 Group N = 241
FLU D-QIV-2 Group N = 229
Subjects with any AE(s), n (%) 66 (27.4 ) 66 (28.8 )
Subjects with grade 3 AE(s), n (%) 6 (2.5 ) 7 (3.1 )
Subjects with related AE(s), n (%) 5 (2.1 ) 3 (1.3 )
Cough 9 (3.7) 13 (5.7)
Bronchitis 11 (4.6) 5 (2.2)
Nasopharyngitis 6 (2.5) 10 (4.4)
Upper respiratory tract infection 4 (1.7) 8 (3.5)
Pharyngitis 5 (2.1) 6 (2.6)
Vomiting 4 (1.7) 5 (2.2)
Tonsillitis 6 (2.5) -
Pyrexia 3 (1.2) 5 (2.2)
Viral infection 6 (2.5) -
Diarrhoea 3 (1.2) 4 (1.7)
Otitis media 3 (1.2) 4 (1.7)
Rhinitis - 5 (2.2)
N = number of subjects with the administered dose n/% = number/percentage of subjects reporting the symptom at least once Grade 3 = event that prevented normal activities Related = event assessed by the investigator as causally related to the study vaccination Counting rule applied: As there were more than 30 subjects per treatment group and ≤ 3 groups, only the 10 most frequent events in each treatment group were listed. -: Implies that adverse event was not reported in the particular group or that the adverse event was reported in the particular group but did not fall within the pre-defined counting rule of 10 most frequent events for that group.
Safety Results: Number (%) of subjects with SAEs during the entire study period (Total Vaccinated cohort)
Serious Adverse Events, n (%) [n considered by the investigator to be related to study medication]
All SAEs FLU D-QIV-1 Group
N = 241 FLU D-QIV-2 Group
N = 229
Subjects with any SAEs, n (%) [n assessed by the investigator as related]
Subjects with fatal SAEs, n (%) [n assessed by the investigator as related]
0 (0.0) [0] 0 (0.0) [0]
Conclusion: For the ATP-I, the geometric mean titre (GMT) for HI antibodies titres at Day 0 ranged between 11.9 and 43.1 in the FLU D-QIV-1 Group (vaccine-primed group), in contrast to between 6.5 and 16.4 in the FLU D-QIV-2 group (vaccine-unprimed group). Post-vaccination, at Day 7, the GMTs ranged between 135.3 and 445.6 in the FLU D-QIV-1 Group, and between 26.1 and 47.5 in the FLU D-QIV-2 Group. In the ATP-I, the SPRs at Day 0 post-vaccination dose 1, across the 4 vaccine strains (A/Christchurch/16/2010, A/Victoria/361/2011, B/Brisbane/60/2008 and B/Hubei-Wujiagang/158/2009) ranged between 12.2% and 40.3% in the FLU D-QIV-1 Group and between 5.9% and 36.6% in the FLU D-QIV-2 Group. At Day 7 post-vaccination dose 1, the SPRs ranged between 86.2% and 96.9% in the FLU D-QIV-1 Group and between 34.4% and 40.2% in the FLU D-QIV-2 Group. The SCRs at Day 7 post-vaccination dose 1, across the 4 vaccine-strains ranged between 76.5% and 94.1% in the FLU D-QIV-1 Group and between 32.2% and 38.6% in the FLU D-QIV-2 Group. At the same time point, the MGI ranged between 6.7 and 15.2 in the FLU D-QIV-1 Group and between 2.9 and 4.6 in the FLU D-QIV-2 Group across the 4 vaccine-strains. Additionally, the protocol-specified analysis of immunogenicity parameters using the ATP-I excluding subjects who had an RT-PCR confirmed influenza infection in study 115345, yielded results which were very similar to the results of the ATP-I analysis inclusive of all eligible subjects. During the 28-day follow-up period after first vaccination, at least one unsolicited adverse event was reported by 66 (27.4%) subjects in FLU D-QIV-1 Group and 66 (28.8%) subjects in FLU D-QIV-2 Group. During the same time period, 6 (2.5%) subjects in FLU D-QIV-1 Group and 7 (3.1%) subjects in FLU D-QIV-2 Group reported grade 3 unsolicited AEs and 5 (2.1%) subjects in FLU D-QIV-1 Group and 3 (1.3%) subjects in FLU D-QIV-2 Group reported unsolicited AEs assessed by the investigator as causally related to study vaccination. During the entire study period, at least 1 SAE was reported by 7 subjects in FLU D-QIV-1 Group and 8 subjects in FLU D-QIV-2 Group. None of them was assessed by the investigator as causally related to study vaccination. There were no fatal SAEs reported throughout the study.