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Trial record 89 of 112 for:    mf59

Safety and Immunogenicity of an Adjuvanted Trivalent Influenza Vaccine in Children 6 to <72 Months of Age in Mexico.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02255279
Recruitment Status : Completed
First Posted : October 2, 2014
Results First Posted : February 3, 2016
Last Update Posted : January 27, 2017
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Vaccines )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Condition Influenza
Interventions Biological: Adjuvanted Trivalent Influenza Vaccine, 1 dose for non-naive subjects (day 1), two doses for naive subjects (day 1 and day 29)
Biological: Non-adjuvanted Trivalent Influenza Vaccine, 1 dose for non-naive subjects (day 1), two doses for naive subjects (day 1 and day 29).
Enrollment 287
Recruitment Details Subjects were enrolled from 3 study centers in Mexico.
Pre-assignment Details All enrolled subjects were included in study.
Arm/Group Title aTIV (6 Months to < 72 Months) TIV (6 Months to < 72 Months)
Hide Arm/Group Description A 0.25 mL (for children 6 to <36 months old) and 0.5 mL (for children ≥36 months to < 72 months old) dose of aTIV to be administered. A 0.25 mL (for children 6 to <36 months old) and 0.5 mL (for children ≥36 months to < 72 months old) dose of TIV to be administered.
Period Title: Overall Study
Started 144 143
Completed 139 134
Not Completed 5 9
Reason Not Completed
Lost to Follow-up             2             2
Protocol Violation             0             1
Withdrawal by Subject             3             6
Arm/Group Title aTIV (6 Months to < 72 Months) TIV (6 Months to < 72 Months) Total
Hide Arm/Group Description A 0.25 mL (for children 6 to <36 months old) and 0.5 mL (for children ≥36 months to < 72 months old) dose of aTIV to be administered. A 0.25 mL (for children 6 to <36 months old) and 0.5 mL (for children ≥36 months to < 72 months old) dose of TIV to be administered. Total of all reporting groups
Overall Number of Baseline Participants 144 143 287
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 144 participants 143 participants 287 participants
29.5  (18.2) 30.1  (19.1) 29.8  (18.6)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 144 participants 143 participants 287 participants
FEMALE
68
  47.2%
72
  50.3%
140
  48.8%
MALE
76
  52.8%
71
  49.7%
147
  51.2%
1.Primary Outcome
Title Number of Naive Subjects 6 to < 36 Months Old Reporting Solicited Local and Systemic Adverse Events (AEs) From Day 1 to Day 7 Following Each Vaccination.
Hide Description Number of naive subjects 6 to < 36 months old reporting solicited local and systemic AEs from Day 1 to Day 7 after first vaccination and from Day 29 to Day 35 after second vaccination.
Time Frame From Day 1 to Day 7 by vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis performed on the Solicited Safety Set.
Arm/Group Title Naive_aTIV (6 to <36 Months) Naive_TIV (6 to <36 Months)
Hide Arm/Group Description:
A 0.25 mL (for children 6 to <36 months old) dose of aTIV to be administered.
A 0.25 mL (for children 6 to <36 months old) dose of TIV to be administered.
Overall Number of Participants Analyzed 68 69
Measure Type: Number
Unit of Measure: Participants
Any Local (Vac-1) 35 20
Any Local (Vac-2, N= 67,67) 21 15
Injection site ecchymosis (Vac-1, N= 65,69) 2 2
Injection site ecchymosis (Vac-2, N= 66,67) 1 1
Injection site induration (Vac-1, N= 66,69) 5 6
Injection site induration (Vac-2, N= 66,67) 3 4
Injection site swelling (Vac-1, N= 65,69) 8 2
Injection site swelling (Vac-2, N= 66,67) 2 2
Injection site erythema (Vac-1, N= 64,69) 9 8
Injection site erythema (Vac-2, N= 66,67) 7 4
Injection site tenderness (Vac-1, N= 66,69) 26 16
Injection site tenderness (Vac-1, N= 66,66) 17 13
Any Systemic (Vac-1) 34 27
Any Systemic (Vac-2, N=67,67) 27 22
Body Temperature (>=40°C) (Vac-1, N= 67,68) 0 0
Body Temperature (>=40°C) (Vac-2, N= 67,67) 0 0
Fever (Vac-1) 7 5
Fever (Vac-2, N= 67,67) 7 2
Change in eating habits (Vac-1, N= 67,69) 14 4
Change in eating habits (Vac-2, N= 66,67) 11 7
Diarrhea (Vac-1, N= 67,69) 15 15
Diarrhea (Vac-2, N= 66,67) 11 11
Irritability (Vac-1, N= 67,69) 18 13
Irritability (Vac-2, N= 66,67) 17 9
Persistent Crying (Vac-1, N= 67,69) 15 11
Persistent Crying (Vac-2, N= 66,67) 11 9
Sleepiness (Vac-1, N= 67,68) 10 11
Sleepiness (Vac-2, N= 65,67) 8 9
Vomiting (Vac-1, N= 67,68) 5 4
Vomiting (Vac-2, N= 65,67) 2 2
Prevention of Pain and or Fever (Vac-1, N= 67,67) 2 2
Prevention of Pain and or Fever (Vac-2, N= 64,67) 3 2
Treatment of Pain and or Fever (Vac-1, N= 67,67) 9 7
Treatment of Pain and or Fever (Vac-1, N= 66,67) 10 2
2.Primary Outcome
Title Number of Non-naive Subjects 6 to < 36 Months Old Reporting Solicited Local and Systemic AEs From Day 1 to Day 7 After Vaccination.
Hide Description Number of non-naive subjects 6 to < 36 months old reporting solicited local and systemic AEs from Day 1 to Day 7 after vaccination.
Time Frame From Day 1 to Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis performed on the Solicited Safety Set.
Arm/Group Title Non-naive_aTIV (6 to <36 Months) Non-naive_TIV (6 to <36 Months)
Hide Arm/Group Description:
A 0.25 mL (for children 6 to <36 months old) dose of aTIV to be administered.
A 0.25 mL (for children 6 to <36 months old) dose of TIV to be administered.
Overall Number of Participants Analyzed 22 22
Measure Type: Number
Unit of Measure: Participants
Any Local 10 7
Injection site ecchymosis 0 1
Injection site induration 2 0
Injection site swelling 1 1
Injection site erythema 2 4
Injection site tenderness (N= 22,21) 9 4
Any Systemic 9 7
Body Temperature (>= 40.0°C) 0 0
Fever 6 1
Change in eating habits 4 3
Diarrhea 3 6
Irritability 4 3
Persistent Crying 1 1
Sleepiness 2 0
Vomiting (N= 21,21) 1 1
Prevention of Pain and or Fever (N= 21,22) 0 0
Treatment of Pain and or Fever (N= 21,22) 2 1
3.Primary Outcome
Title Number of Naive Subjects ≥ 36 Months to < 72 Months Old Reporting Solicited Local and Systemic AEs From Day 1 to Day 7 Following Each Vaccination.
Hide Description Number of naive subjects ≥ 36 months to < 72 months old reporting solicited local and systemic AEs from Day 1 to Day 7 after first vaccination and from Day 29 to Day 35 after second vaccination.
Time Frame From Day 1 to Day 7 by vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis performed on the Solicited Safety Set.
Arm/Group Title Naive_aTIV (≥36 Months to < 72 Months) Naive_TIV (≥36 Months to < 72 Months)
Hide Arm/Group Description:
A 0.5 mL (for children ≥36 months to < 72 months old) dose of aTIV to be administered.
A 0.5 mL (for children ≥36 months to < 72 months old) dose of TIV to be administered.
Overall Number of Participants Analyzed 6 4
Measure Type: Number
Unit of Measure: Participants
Any Local (Vac-1) 5 2
Any Local (Vac-2, N= 6,3) 4 2
Injection site ecchymosis (Vac-1) 0 0
Injection site ecchymosis (Vac-2, N= 6,3) 0 0
Injection site induration (Vac-1) 2 1
Injection site induration (Vac-2, N= 6,3) 2 0
Injection site swelling (Vac-1) 2 0
Injection site swelling (Vac-2, N= 6,3) 0 0
Injection site erythema (Vac-1) 1 0
Injection site erythema (Vac-2, N= 6,3) 0 0
Injection site pain (Vac-1) 3 2
Injection site pain (Vac-2, N= 6,3) 3 2
Any Systemic (Vac-1) 3 1
Any Systemic (Vac-2, N= 6,3) 2 0
Fatigue (Vac-1) 1 1
Fatigue (Vac-2, N= 6,3) 2 0
Myalgia (Vac-1) 2 0
Myalgia (Vac-2, N= 6,3) 1 0
Arthralgia (Vac-1) 0 0
Arthralgia (Vac-2, N= 6,2) 0 0
Headache (Vac-1) 1 1
Headache (Vac-2, N= 6,2) 1 0
Body Temperature (>= 40.0°C) (Vac-1) 0 0
Body Temperature (>= 40.0°C) (Vac-2, N= 6,3) 0 0
Fever (Vac-1) 2 0
Fever (Vac-2, N= 6,3) 1 0
Chills (Vac-1) 0 0
Chills (Vac-2, N= 6,3) 0 0
Change in Eating Habits (Vac-1, N= 5,4) 2 0
Change in Eating Habits (Vac-2, N= 6,3) 0 0
Diarrhea (Vac-1) 0 0
Diarrhea (Vac-2, N= 6,3) 0 0
Vomiting (Vac-1) 0 0
Vomiting (Vac-2, N= 6,3) 0 0
Prevention of Pain and or Fever (Vac-1, N= 6,2) 1 0
Prevention of Pain and or Fever (Vac-2, N= 4,2) 0 0
Treatment of Pain and or Fever (Vac-1, N= 6,2) 0 0
Treatment of Pain and or Fever (Vac-2, N= 5,2) 0 0
4.Primary Outcome
Title Number of Non-naive Subjects ≥36 Months to < 72 Months Old Reporting Solicited Local and Systemic AEs From Day 1 to Day 7 Following Each Vaccination.
Hide Description Number of non-naive subjects ≥36 months to < 72 months old reporting solicited local and systemic AEs from Day 1 to Day 7 after vaccination.
Time Frame From Day 1 to Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis performed on the Solicited Safety Set.
Arm/Group Title Non-naive_aTIV (≥36 Months to < 72 Months) Non-naive_TIV (≥36 Months to < 72 Months)
Hide Arm/Group Description:
A 0.5 mL (for children ≥36 months to < 72 months old) dose of aTIV to be administered.
A 0.5 mL (for children ≥36 months to < 72 months old) dose of TIV to be administered.
Overall Number of Participants Analyzed 44 41
Measure Type: Number
Unit of Measure: Participants
Any Local 17 20
Injection site ecchymosis 2 1
Injection site induration 6 3
Injection site swelling 4 3
Injection site erythema (N= 43,40) 6 7
Injection site pain (N= 44,40) 14 16
Injection site tenderness 0 0
Any Systemic 15 7
Fatigue (N= 44,40) 6 2
Myalgia (N= 44,40) 7 0
Arthralgia (N= 44,40) 4 0
Headache (N= 44,40) 3 2
Body Temperature (>= 40.0°C) (N= 44,40) 0 0
Fever 2 1
Chills (N= 44,40) 2 0
Change in eating habits (N= 44,39) 8 3
Diarrhea (N= 44,39) 4 3
Vomiting (N= 44,40) 2 1
Prevention of Pain and or Fever (N= 42,40) 0 0
Treatment of Pain and or Fever (N=42,40) 5 0
5.Primary Outcome
Title Number of Naive Subjects Aged 6 to < 72 Months Reporting All Unsolicited AEs From Day 1 to Day 50.
Hide Description Number of naive subjects aged 6 to < 72 months reporting all unsolicited AEs, medically attended AEs, AE leading to study withdrawal and serious AEs (SAEs) from Day 1 to Day 50.
Time Frame From Day 1 to Day 50
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis performed on the Unsolicited Safety Set.
Arm/Group Title Naive_aTIV (6 Months to < 72 Months) Naive_TIV (6 Months to < 72 Months)
Hide Arm/Group Description:
A 0.25 mL (for children 6 to <36 months old) and 0.5 mL (for children ≥36 months to < 72 months old) dose of aTIV to be administered.
A 0.25 mL (for children 6 to <36 months old) and 0.5 mL (for children ≥36 months to < 72 months old) dose of TIV to be administered.
Overall Number of Participants Analyzed 74 73
Measure Type: Number
Unit of Measure: Participants
Any AE 33 28
At least Possibly related AE 4 4
SAE 0 0
At least possibly related SAE 0 0
AE leading to study withdrawal 0 0
Medically attended AE 26 25
Death 0 0
6.Primary Outcome
Title Number of Non-naive Subjects Aged 6 to < 72 Months Reporting All Unsolicited AEs From Day 1 to Day 22
Hide Description Number of non-naive subjects aged 6 to < 72 months reporting all unsolicited AEs, medically attended AEs, AE leading to study withdrawal and SAEs from Day 1 to Day 22.
Time Frame From Day 1 to Day 22
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis performed on the Unsolicited Safety Set.
Arm/Group Title Non naive_aTIV (6 Months to < 72 Months) Non naive_TIV (6 Months to < 72 Months)
Hide Arm/Group Description:
A 0.25 mL (for children 6 to <36 months old) and 0.5 mL (for children ≥36 months to < 72 months old) dose of aTIV to be administered.
A 0.25 mL (for children 6 to <36 months old) and 0.5 mL (for children ≥36 months to < 72 months old) dose of TIV to be administered.
Overall Number of Participants Analyzed 66 64
Measure Type: Number
Unit of Measure: Participants
Any AE 9 6
At least Possibly related AE 2 0
SAE 0 0
At least possibly related SAE 0 0
AE leading to study withdrawal 0 0
Medically attended AE 3 4
Death 0 0
7.Primary Outcome
Title Geometric Mean Titers (GMTs), in All Three Homologous Virus Strains in Subjects 6 to < 72 Months of Age.
Hide Description

Antibody response was assessed in terms of GMTs in all three homologous virus strains, 21 days after last immunization, in subjects 6 to <72 months of age.

The study is considered a success if the 21 days after last immunization GMT ratios of aTIV relative to TIV demonstrate as non-inferior with the lower limit (LL) of the two sided 95% confidence interval (CI) above 0.67 (-0.176 on log10 scale) for each vaccine strain (Center for Biologics Evaluation and Research {CBER} Guideline on Seasonal Vaccines May 2007).

Time Frame Day 1 and Day 22 (vaccine non-naïve subjects) or Day 50 (vaccine naïve subjects) post vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis performed on the Per Protocol Set.
Arm/Group Title aTIV (6 Months to < 72 Months) TIV (6 Months to < 72 Months)
Hide Arm/Group Description:
A 0.25 mL (for children 6 to <36 months old) and 0.5 mL (for children ≥36 months to < 72 months old) dose of aTIV to be administered.
A 0.25 mL (for children 6 to <36 months old) and 0.5 mL (for children ≥36 months to < 72 months old) dose of TIV to be administered.
Overall Number of Participants Analyzed 114 112
Geometric Mean (95% Confidence Interval)
Unit of Measure: Titers
A/H1N1 (Day 1) (N= 113,112)
14
(11 to 19)
15
(11 to 20)
A/H1N1 (Day 22 or Day 50)
675
(536 to 849)
166
(132 to 208)
A/H3N2 (Day 1)
59
(40 to 86)
55
(38 to 81)
A/H3N2 (Day 22 or Day 50)
1280
(1077 to 1521)
495
(417 to 588)
B (Day 1)
7.47
(6.41 to 8.71)
6.92
(5.95 to 8.06)
B (Day 22 or Day 50)
76
(61 to 93)
16
(13 to 20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection aTIV (6 Months to < 72 Months), TIV (6 Months to < 72 Months)
Comments Geometric mean titers (GMTs), in H1N1 strain of all the tree strains in Subjects 6 to < 72 months of Age.
Type of Statistical Test Non-Inferiority or Equivalence
Comments

Hypothesis: Demonstrate non-inferiority (NI) of aTIV to TIV:

H0 : μAi - μBi ≤ -0.176 (Null) H1 : μAi – μBi >-0.176 (alternative) (i= H1N1, H3N2, B) μA and μB are means of log10-transformed titers 21 days after last vaccination of the aTIV & TIV vaccine groups respectively. NI is claimed if LL of 95% CI for GMT ratios is >0.67.

Significance level is α = 2.5% (1-sided), which needs no further adjustment for multiplicity as to reach NI, above hypothesis needs to be rejected for all 3 strains.

Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of GMTs
Estimated Value 4.06
Confidence Interval (2-Sided) 95%
3.00 to 5.51
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection aTIV (6 Months to < 72 Months), TIV (6 Months to < 72 Months)
Comments Geometric mean titers (GMTs), in H3N2 strain of all three homologous virus strains in Subjects 6 to < 72 months of Age.
Type of Statistical Test Non-Inferiority or Equivalence
Comments

Hypothesis: Demonstrate non-inferiority (NI) of aTIV to TIV:

H0 : μAi - μBi ≤ -0.176 (Null) H1 : μAi - μBi >-0.176 (alternative) (i= H1N1, H3N2, B) μA and μB are means of log10-transformed titers 21 days after last vaccination of the aTIV & TIV vaccine groups respectively. NI is claimed if LL of 95% CI for GMT ratios is >0.67.

Significance level is α = 2.5% (1-sided), which needs no further adjustment for multiplicity as to reach NI, above hypothesis needs to be rejected for all 3 strains.

Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of GMTs
Estimated Value 2.58
Confidence Interval (2-Sided) 95%
2.05 to 3.25
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection aTIV (6 Months to < 72 Months), TIV (6 Months to < 72 Months)
Comments Geometric mean titers (GMTs), in B strain of all three homologous virus strains in Subjects 6 to < 72 months of Age.
Type of Statistical Test Non-Inferiority or Equivalence
Comments

Hypothesis: Demonstrate non-inferiority (NI) of aTIV to TIV:

H0 : μAi - μBi ≤ -0.176 (Null) H1 : μAi - μBi >-0.176 (alternative) (i= H1N1, H3N2, B) μA and μB are means of log10-transformed titers 21 days after last vaccination of the aTIV & TIV vaccine groups respectively. NI is claimed if LL of 95% CI for GMT ratios is >0.67.

Significance level is α = 2.5% (1-sided), which needs no further adjustment for multiplicity as to reach NI, above hypothesis needs to be rejected for all 3 strains.

Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of GMTs
Estimated Value 4.67
Confidence Interval (2-Sided) 95%
3.52 to 6.20
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Percentages of Subjects Achieving Seroconversion in Hemagglutination Inhibition (HI) Titers and Vaccine Group Differences at Day 1 and 21 Days After Last Vaccination With aTIV or TIV in Naive and Non-naive Subjects.
Hide Description Percentages of subjects with seroconversion in all three homologous virus strains, 21 days after last immunization, in subjects 6 to <72 months of age, defined as: HI ≥ 40 subject with a pre-vaccination HI titer <10; a minimum 4-fold increase HI titer for subjects with a prevaccination HI titer ≥10, on Day 22 (non-naive subjects) or Day 50 (naive subjects), as applicable.
Time Frame Day 1 and Day 22 (vaccine non-naive subjects) or Day 50 (vaccine naive subjects) post vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis performed on the Per Protocol Set.
Arm/Group Title aTIV (6 Months to < 72 Months) TIV (6 Months to < 72 Months)
Hide Arm/Group Description:
A 0.25 mL (for children 6 to <36 months old) and 0.5 mL (for children ≥36 months to < 72 months old) dose of aTIV to be administered.
A 0.25 mL (for children 6 to <36 months old) and 0.5 mL (for children ≥36 months to < 72 months old) dose of TIV to be administered.
Overall Number of Participants Analyzed 114 112
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentages of subjects
H1N1 strain (N= 113,112)
90
(83.2 to 95)
75
(65.9 to 82.7)
H3N2 strain
77
(68.4 to 84.5)
67
(57.4 to 75.6)
B strain
78
(69.4 to 85.3)
22
(15 to 31.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection aTIV (6 Months to < 72 Months), TIV (6 Months to < 72 Months)
Comments Percentage of subjects achieving seroconversion in H1N1 strain after last vaccination with aTIV or TIV in naïve and non-naive subjects.
Type of Statistical Test Non-Inferiority or Equivalence
Comments

The following hypotheses should be tested to demonstrate non-inferiority of aTIV to TIV:

H0i: πi1 > πi2-0.1 vs. H1i: πi1 > πi2- 0.1 where H0i and H1i represent the null and the alternative hypothesis (respectively) of the non- inferiority objective and πi1 and πi2 represent the seroresponse rates 21 days after last immunization of the aTIV and TIV vaccine groups respectively in the i-th strain (H1N1, H3N2, B). The non-inferiority criterion is -0.1 (i.e., -10%).

Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Loglinear model
Comments Binary data were analyzed using loglinear models with a qualitative factor for vaccine group (αik, i = A, B) and center (δlk, k=1).
Method of Estimation Estimation Parameter Vaccine Group Differences
Estimated Value 17
Confidence Interval (2-Sided) 95%
8.1 to 26.3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection aTIV (6 Months to < 72 Months), TIV (6 Months to < 72 Months)
Comments Percentage of subjects achieving seroconversion in H3N2 strain after last vaccination with aTIV or TIV in naive and non-naive subjects.
Type of Statistical Test Non-Inferiority or Equivalence
Comments

The following hypotheses should be tested to demonstrate non-inferiority of aTIV to TIV:

H0i: πi1 > πi2-0.1 vs. H1i: πi1 > πi2- 0.1 where H0i and H1i represent the null and the alternative hypothesis (respectively) of the non- inferiority objective and πi1 and πi2 represent the seroresponse rates 21 days after last immunization of the aTIV and TIV vaccine groups respectively in the i-th strain (H1N1, H3N2, B). The non-inferiority criterion is -0.1 (i.e., -10%).

Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Loglinear model
Comments Binary data were analyzed using loglinear models with a qualitative factor for vaccine group (αik, i = A, B) and center (δlk, k=1).
Method of Estimation Estimation Parameter Vaccine Group Differences
Estimated Value 10
Confidence Interval (2-Sided) 95%
-1.8 to 21
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection aTIV (6 Months to < 72 Months), TIV (6 Months to < 72 Months)
Comments Percentage of subjects achieving seroconversion in B strains after last vaccination with aTIV or TIV in naïve and non naive subjects.
Type of Statistical Test Non-Inferiority or Equivalence
Comments

The following hypotheses should be tested to demonstrate non-inferiority of aTIV to TIV:

H0i: πi1 > πi2-0.1 vs. H1i: πi1 > πi2- 0.1 where H0i and H1i represent the null and the alternative hypothesis (respectively) of the non- inferiority objective and πi1 and πi2 represent the seroresponse rates 21 days after last immunization of the aTIV and TIV vaccine groups respectively in the i-th strain (H1N1, H3N2, B). The non-inferiority criterion is -0.1 (i.e., -10%).

Statistical Test of Hypothesis P-Value [Not Specified]
Comments [Not Specified]
Method Loglinear model
Comments Binary data were analyzed using loglinear models with a qualitative factor for vaccine group (αik, i = A, B) and center (δlk, k=1).
Method of Estimation Estimation Parameter Vaccine Group Differences
Estimated Value 58
Confidence Interval (2-Sided) 95%
47.5 to 68.5
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Geometric Mean Ratios (GMRs) of HI and Vaccine Group Differences at Day 1 and 21 Days After Last Vaccination With aTIV or TIV in Naive and Non-naive Subjects.
Hide Description GMRs of HI, day 22/day 1 (non-naive subjects) or day 50/day 1 (naive subjects) in all three homologous virus strains, 21 days after last immunization, in subjects 6 to <72 months of age. As the non-inferiority of aTIV to TIV has been established, GMT ratio of aTIV relative to TIV in all three homologous virus strains, 21 days after last immunization in subjects 6 to <72 months of age was evaluated using margins greater than the non-inferiority cut-off of 0.67.
Time Frame Day 1 and Day 22 (vaccine non-naive subjects) or Day 50 (vaccine naive subjects) post vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis performed on the Per Protocol Set.
Arm/Group Title aTIV (6 Months to < 72 Months) TIV (6 Months to < 72 Months)
Hide Arm/Group Description:
A 0.25 mL (for children 6 to <36 months old) and 0.5 mL (for children ≥36 months to < 72 months old) dose of aTIV to be administered.
A 0.25 mL (for children 6 to <36 months old) and 0.5 mL (for children ≥36 months to < 72 months old) dose of TIV to be administered.
Overall Number of Participants Analyzed 114 112
Geometric Mean (95% Confidence Interval)
Unit of Measure: Ratios
H1N1 strain (N=113,112)
46
(34 to 62)
11
(8.12 to 15)
H3N2 strain
21
(16 to 28)
8.39
(6.26 to 11)
B strain
10
(8.25 to 13)
2.30
(1.84 to 2.87)
10.Secondary Outcome
Title Percentages of Subjects With a HI Titer ≥ 40, ≥110 and ≥330 and Vaccine Group Differences at Day 1 and 21 Days After Last Vaccination With aTIV or TIV in Naive and Non-naive Subjects.
Hide Description Percentage of subjects with a HI titer ≥ 40, ≥110 and ≥330 on Day 1, Day 22 (non naïve subjects) or Day 50 (naïve subjects), in all three homologous virus strains, 21 days after last immunization, in subjects 6 to <72 months of age.
Time Frame Day 1 and Day 22 (vaccine non-naive subjects) or Day 50 (vaccine naive subjects) post vaccination
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis performed on the Per Protocol Set.
Arm/Group Title aTIV (6 Months to < 72 Months) TIV (6 Months to < 72 Months)
Hide Arm/Group Description:
A 0.25 mL (for children 6 to <36 months old) and 0.5 mL (for children ≥36 months to < 72 months old) dose of aTIV to be administered.
A 0.25 mL (for children 6 to <36 months old) and 0.5 mL (for children ≥36 months to < 72 months old) dose of TIV to be administered.
Overall Number of Participants Analyzed 114 112
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of subjects
H1N1 strain (HI titer ≥ 40, Day 1) (N=113,112)
32
(23.4 to 41.3)
33
(24.4 to 42.6)
H1N1 strain (HI titer ≥ 40, Day 22 or Day 50)
99
(95.2 to 99.98)
88
(81 to 93.7)
H1N1 strain (HI titer ≥ 110, Day 1) (N=113,112)
19
(11.9 to 27)
20
(12.7 to 28.2)
H1N1 strain (HI titer ≥ 110, Day 22 or Day 50)
96
(90.1 to 98.6)
68
(58.4 to 76.4)
H1N1 strain (HI titer ≥ 330, Day 1)
4
(1.5 to 10)
7
(3.1 to 13.6)
H1N1 strain (HI titer ≥ 330, Day 22 or Day 50)
78
(69.4 to 85.3)
37
(27.7 to 46.2)
H3N2 strain (HI titer ≥ 40, Day 1)
56
(46.5 to 65.4)
58
(48.3 to 67.3)
H3N2 strain (HI titer ≥ 40, Day 22 or Day 50)
100
(96.8 to 100)
97
(92.4 to 99.4)
H3N2 strain (HI titer ≥ 110, Day 1)
44
(34.6 to 53.5)
44
(34.4 to 53.4)
H3N2 strain (HI titer ≥ 110, Day 22 or Day 50)
99
(95.2 to 99.98)
84
(75.8 to 90.2)
H3N2 strain (HI titer ≥ 330, Day 1)
33
(24.8 to 42.8)
30
(22 to 39.8)
H3N2 strain (HI titer ≥ 330, Day 22 or Day 50)
86
(78.2 to 91.8)
61
(51 to 69.8)
B strain (HI titer ≥ 40, Day 1)
9
(4.3 to 15.5)
9
(4.4 to 15.8)
B strain (HI titer ≥ 40, Day 22 or Day 50)
84
(76.2 to 90.4)
32
(23.6 to 41.6)
B strain (HI titer ≥ 110, Day 1)
2
(0.21 to 6.2)
1
(0.02 to 4.9)
B strain (HI titer ≥ 110, Day 22 or Day 50)
43
(33.7 to 52.6)
6
(2.5 to 12.5)
B strain (HI titer ≥ 330, Day 1)
0
(0 to 3.2)
0
(0 to 3.2)
B strain (HI titer ≥ 330, Day 22 or Day 50)
8
(3.7 to 14.5)
0
(0 to 3.2)
Time Frame Throughout the study; Day 1 - Day 50 (naive subjects) and Day 1 - Day 22 (non-naive subjects).
Adverse Event Reporting Description

Solicited AEs were collected by the subject parent(s)/legal guardian(s) for 7 days from the day of vaccination/s (Day 1 & Day 29 for naive; Day 1 for non-naive). Unsolicited AEs were collected from Day 1 to Day 50 for naive, from Day 1 to Day 22 for non-naive.

All AEs were monitored until resolution or the investigator assesses them as stable.

 
Arm/Group Title Naive_aTIV (6 Months to < 72 Months) Naive_TIV (6 Months to < 72 Months) Non-naive_aTIV (6 Months to < 72 Months) Non-naive_TIV (6 Months to < 72 Months)
Hide Arm/Group Description A 0.25 mL (for children 6 to <36 months old) and 0.5 mL (for children ≥36 months to < 72 months old) dose of aTIV to be administered (Naive).

A 0.25 mL (for children 6 to <36 months old) and 0.5 mL (for children ≥36 months to < 72 months old) dose of TIV to be administered (Naive).

Enrolled subjects- 79 Exposed subjects- 78 Reason for discrepancy- Before vaccination one subject was withdrawn from study because of the suspected egg allergy.

A 0.25 mL (for children 6 to <36 months old) and 0.5 mL (for children ≥36 months to < 72 months old) dose of aTIV to be administered (Non-naive). A 0.25 mL (for children 6 to <36 months old) and 0.5 mL (for children ≥36 months to < 72 months old) dose of TIV to be administered (Non-naive).
All-Cause Mortality
Naive_aTIV (6 Months to < 72 Months) Naive_TIV (6 Months to < 72 Months) Non-naive_aTIV (6 Months to < 72 Months) Non-naive_TIV (6 Months to < 72 Months)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Naive_aTIV (6 Months to < 72 Months) Naive_TIV (6 Months to < 72 Months) Non-naive_aTIV (6 Months to < 72 Months) Non-naive_TIV (6 Months to < 72 Months)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/77 (0.00%)   0/78 (0.00%)   0/67 (0.00%)   0/64 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Naive_aTIV (6 Months to < 72 Months) Naive_TIV (6 Months to < 72 Months) Non-naive_aTIV (6 Months to < 72 Months) Non-naive_TIV (6 Months to < 72 Months)
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   58/77 (75.32%)   52/78 (66.67%)   35/67 (52.24%)   31/64 (48.44%) 
Gastrointestinal disorders         
Diarrhoea  1  22/77 (28.57%)  21/78 (26.92%)  7/67 (10.45%)  9/64 (14.06%) 
Vomiting  1  7/77 (9.09%)  6/78 (7.69%)  4/67 (5.97%)  2/64 (3.13%) 
General disorders         
Crying * 1  20/77 (25.97%)  15/78 (19.23%)  1/67 (1.49%)  1/64 (1.56%) 
Fatigue * 1  3/77 (3.90%)  1/78 (1.28%)  6/67 (8.96%)  2/64 (3.13%) 
Injection site erythema  1  13/77 (16.88%)  11/78 (14.10%)  8/67 (11.94%)  11/64 (17.19%) 
Injection site induration  1  10/77 (12.99%)  10/78 (12.82%)  8/67 (11.94%)  3/64 (4.69%) 
Injection site pain * 1  33/77 (42.86%)  25/78 (32.05%)  23/67 (34.33%)  20/64 (31.25%) 
Injection site swelling  1  12/77 (15.58%)  2/78 (2.56%)  5/67 (7.46%)  4/64 (6.25%) 
Pyrexia * 1  16/77 (20.78%)  11/78 (14.10%)  9/67 (13.43%)  2/64 (3.13%) 
Infections and infestations         
Conjunctivitis * 1  0/77 (0.00%)  4/78 (5.13%)  0/67 (0.00%)  0/64 (0.00%) 
Gastroenteritis * 1  4/77 (5.19%)  3/78 (3.85%)  0/67 (0.00%)  0/64 (0.00%) 
Nasopharyngitis * 1  16/77 (20.78%)  8/78 (10.26%)  2/67 (2.99%)  2/64 (3.13%) 
Pharyngitis * 1  6/77 (7.79%)  10/78 (12.82%)  0/67 (0.00%)  0/64 (0.00%) 
Musculoskeletal and connective tissue disorders         
Myalgia * 1  2/77 (2.60%)  0/78 (0.00%)  7/67 (10.45%)  0/64 (0.00%) 
Arthralgia * 1  0/77 (0.00%)  0/78 (0.00%)  4/67 (5.97%)  0/64 (0.00%) 
Nervous system disorders         
Somnolence * 1  16/77 (20.78%)  14/78 (17.95%)  2/67 (2.99%)  0/64 (0.00%) 
Psychiatric disorders         
Eating disorder * 1  20/77 (25.97%)  9/78 (11.54%)  12/67 (17.91%)  6/64 (9.38%) 
Irritability  1  25/77 (32.47%)  17/78 (21.79%)  4/67 (5.97%)  3/64 (4.69%) 
Respiratory, thoracic and mediastinal disorders         
Cough * 1  6/77 (7.79%)  8/78 (10.26%)  2/67 (2.99%)  0/64 (0.00%) 
Rhinorrhoea * 1  2/77 (2.60%)  4/78 (5.13%)  0/67 (0.00%)  1/64 (1.56%) 
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (19.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis’ agreement with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publications of the pooled data (i.e., data from all sites) in the clinical trial.
Results Point of Contact
Name/Title: Posting Director
Organization: Novartis Vaccines
Responsible Party: Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier: NCT02255279     History of Changes
Other Study ID Numbers: V70_50
First Submitted: September 30, 2014
First Posted: October 2, 2014
Results First Submitted: January 4, 2016
Results First Posted: February 3, 2016
Last Update Posted: January 27, 2017