Trial Outcomes & Findings for Immunogenicity and Safety of Fluzone® Quadrivalent, Southern Hemisphere 2015 Formulation (Intramuscular Route) (NCT NCT03546192)

Last Updated: 2022-03-29

Results Overview

Anti-influenza antibodies were measured using hemagglutination-inhibition (HAI) assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, B Yamagata lineage. Seroprotection was defined as an antibody titer \>=40 (1/dilution \[dil\]) at pre-vaccination and post-vaccination.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

120 participants

Primary outcome timeframe

Day 0 (pre-vaccination) and Day 21 (post-vaccination)

Results posted on

2022-03-29

Participant Flow

Study participants were enrolled in 3 centers in the Philippines from 17 June 2015 to 26 June 2015.

A total of 120 participants (60 for each group) were enrolled and vaccinated in the study.

Participant milestones

Participant milestones
Measure	Fluzone Quadrivalent Influenza Vaccine: 18 to 60 Years Participants aged 18 to 60 years received one 0.5-mL dose of Fluzone Quadrivalent influenza vaccine, intramuscularly, at Day 0.	Fluzone Quadrivalent Influenza Vaccine: 61 Years or Older Participants aged 61 years or older received one 0.5-mL dose of Fluzone Quadrivalent influenza vaccine, intramuscularly, at Day 0.
Overall Study STARTED	60	60
Overall Study COMPLETED	60	60
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Immunogenicity and Safety of Fluzone® Quadrivalent, Southern Hemisphere 2015 Formulation (Intramuscular Route)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Fluzone Quadrivalent Influenza Vaccine: 18 to 60 Years n=60 Participants Participants aged 18 to 60 years received one 0.5-mL dose of Fluzone Quadrivalent influenza vaccine, intramuscularly, at Day 0.	Fluzone Quadrivalent Influenza Vaccine: 61 Years or Older n=60 Participants Participants aged 61 years or older received one 0.5-mL dose of Fluzone Quadrivalent influenza vaccine, intramuscularly, at Day 0.	Total n=120 Participants Total of all reporting groups
Age, Continuous	35.3 years STANDARD_DEVIATION 13.9 • n=5 Participants	68.0 years STANDARD_DEVIATION 5.4 • n=7 Participants	51.7 years STANDARD_DEVIATION 19.5 • n=5 Participants
Sex: Female, Male Female	35 Participants n=5 Participants	45 Participants n=7 Participants	80 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	15 Participants n=7 Participants	40 Participants n=5 Participants
Region of Enrollment Philippines	60 Participants n=5 Participants	60 Participants n=7 Participants	120 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 0 (pre-vaccination) and Day 21 (post-vaccination)

Population: Immunogenicity analysis set included all participants who received one dose of study medication, had pre-and post-vaccination titers available and had not received vaccination against influenza in the previous 12 months if administered in the context of a clinical trial or a flu vaccination campaign.

Outcome measures

Outcome measures
Measure	Fluzone Quadrivalent Influenza Vaccine: 18 to 60 Years n=60 Participants Participants aged 18 to 60 years received one 0.5-mL dose of Fluzone Quadrivalent influenza vaccine, intramuscularly, at Day 0.	Fluzone Quadrivalent Influenza Vaccine: 61 Years or Older n=60 Participants Participants aged 61 years or older received one 0.5-mL dose of Fluzone Quadrivalent influenza vaccine, intramuscularly, at Day 0.
Number of Participants With Seroprotection to Influenza Vaccine Antigens at Day 0 (Pre-vaccination) and Day 21 (Post-vaccination) A/H1N1 (Pre-Vaccination)	41 Participants	37 Participants
Number of Participants With Seroprotection to Influenza Vaccine Antigens at Day 0 (Pre-vaccination) and Day 21 (Post-vaccination) A/H1N1 (Day 21 Post-Vaccination)	60 Participants	60 Participants
Number of Participants With Seroprotection to Influenza Vaccine Antigens at Day 0 (Pre-vaccination) and Day 21 (Post-vaccination) A/H3N2 (Pre-Vaccination)	26 Participants	27 Participants
Number of Participants With Seroprotection to Influenza Vaccine Antigens at Day 0 (Pre-vaccination) and Day 21 (Post-vaccination) A/H3N2 (Day 21 Post-Vaccination)	60 Participants	59 Participants
Number of Participants With Seroprotection to Influenza Vaccine Antigens at Day 0 (Pre-vaccination) and Day 21 (Post-vaccination) B Victoria (Pre-Vaccination)	48 Participants	37 Participants
Number of Participants With Seroprotection to Influenza Vaccine Antigens at Day 0 (Pre-vaccination) and Day 21 (Post-vaccination) B Victoria (Day 21 Post-Vaccination)	60 Participants	60 Participants
Number of Participants With Seroprotection to Influenza Vaccine Antigens at Day 0 (Pre-vaccination) and Day 21 (Post-vaccination) B Yamagata (Pre-Vaccination)	57 Participants	49 Participants
Number of Participants With Seroprotection to Influenza Vaccine Antigens at Day 0 (Pre-vaccination) and Day 21 (Post-vaccination) B Yamagata (Day 21 Post-Vaccination)	60 Participants	60 Participants

PRIMARY outcome

Timeframe: Day 0 (pre-vaccination) and Day 21 (post-vaccination)

Population: Analysis was performed on the Immunogenicity analysis set.

Anti-influenza antibodies were measured using a HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, B Yamagata lineage.

Outcome measures

Outcome measures
Measure	Fluzone Quadrivalent Influenza Vaccine: 18 to 60 Years n=60 Participants Participants aged 18 to 60 years received one 0.5-mL dose of Fluzone Quadrivalent influenza vaccine, intramuscularly, at Day 0.	Fluzone Quadrivalent Influenza Vaccine: 61 Years or Older n=60 Participants Participants aged 61 years or older received one 0.5-mL dose of Fluzone Quadrivalent influenza vaccine, intramuscularly, at Day 0.
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies at Day 0 (Pre-vaccination) and Day 21 (Post-vaccination) A/H1N1 (Pre-Vaccination)	74.6 Titers (1/dilutions [dil]) Interval 49.9 to 112.0	48.4 Titers (1/dilutions [dil]) Interval 33.2 to 70.5
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies at Day 0 (Pre-vaccination) and Day 21 (Post-vaccination) A/H1N1 (Day 21 Post-Vaccination)	2009 Titers (1/dilutions [dil]) Interval 1648.0 to 2448.0	1083 Titers (1/dilutions [dil]) Interval 813.0 to 1442.0
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies at Day 0 (Pre-vaccination) and Day 21 (Post-vaccination) A/H3N2 (Pre-Vaccination)	27.8 Titers (1/dilutions [dil]) Interval 19.3 to 39.9	34.4 Titers (1/dilutions [dil]) Interval 24.6 to 48.1
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies at Day 0 (Pre-vaccination) and Day 21 (Post-vaccination) A/H3N2 (Day 21 Post-Vaccination)	532 Titers (1/dilutions [dil]) Interval 390.0 to 726.0	723 Titers (1/dilutions [dil]) Interval 525.0 to 994.0
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies at Day 0 (Pre-vaccination) and Day 21 (Post-vaccination) B Victoria (Pre-Vaccination)	80.0 Titers (1/dilutions [dil]) Interval 58.6 to 109.0	44.9 Titers (1/dilutions [dil]) Interval 32.3 to 62.4
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies at Day 0 (Pre-vaccination) and Day 21 (Post-vaccination) B Victoria (Day 21 Post-Vaccination)	1052 Titers (1/dilutions [dil]) Interval 849.0 to 1303.0	835 Titers (1/dilutions [dil]) Interval 654.0 to 1066.0
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies at Day 0 (Pre-vaccination) and Day 21 (Post-vaccination) B Yamagata (Pre-Vaccination)	209 Titers (1/dilutions [dil]) Interval 154.0 to 283.0	118 Titers (1/dilutions [dil]) Interval 86.0 to 161.0
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies at Day 0 (Pre-vaccination) and Day 21 (Post-vaccination) B Yamagata (Day 21 Post-Vaccination)	2242 Titers (1/dilutions [dil]) Interval 1828.0 to 2749.0	1070 Titers (1/dilutions [dil]) Interval 835.0 to 1371.0

PRIMARY outcome

Timeframe: Day 0 (pre-vaccination), Day 21 (Post-vaccination)

Population: Analysis was performed on the Immunogenicity analysis set.

Anti-influenza antibodies were measured using HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, B Yamagata lineage. Geometric mean titer ratio was calculated as geometric mean titer at Day 21 divided by geometric mean titer at day 0 for each specified group.

Outcome measures

Outcome measures
Measure	Fluzone Quadrivalent Influenza Vaccine: 18 to 60 Years n=60 Participants Participants aged 18 to 60 years received one 0.5-mL dose of Fluzone Quadrivalent influenza vaccine, intramuscularly, at Day 0.	Fluzone Quadrivalent Influenza Vaccine: 61 Years or Older n=60 Participants Participants aged 61 years or older received one 0.5-mL dose of Fluzone Quadrivalent influenza vaccine, intramuscularly, at Day 0.
Geometric Mean Titer Ratio (GMTR) of Influenza Vaccine Antibodies A/H1N1	26.9 ratio Interval 17.1 to 42.4	22.4 ratio Interval 14.7 to 34.0
Geometric Mean Titer Ratio (GMTR) of Influenza Vaccine Antibodies A/H3N2	19.1 ratio Interval 12.5 to 29.4	21.0 ratio Interval 14.0 to 31.5
Geometric Mean Titer Ratio (GMTR) of Influenza Vaccine Antibodies B Victoria	13.1 ratio Interval 9.72 to 17.8	18.6 ratio Interval 13.6 to 25.4
Geometric Mean Titer Ratio (GMTR) of Influenza Vaccine Antibodies B Yamagata	10.7 ratio Interval 7.95 to 14.5	9.08 ratio Interval 6.49 to 12.7

PRIMARY outcome

Timeframe: 21 days post-vaccination

Population: Analysis was performed on the Immunogenicity analysis set.

Anti-influenza antibodies were measured using HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, B Yamagata lineage. Seroconversion was defined as participants with a pre-vaccination titer \<10 (1/dil) and a post-vaccination titer \>= 40 (1/dil). Significant increase was defined as a pre-vaccination titer \>= 10 (1/dil) and \>= 4-fold increase in post vaccination titer. Number of participants with seroconversion or significant increase to Influenza vaccine antigens were reported.

Outcome measures

Outcome measures
Measure	Fluzone Quadrivalent Influenza Vaccine: 18 to 60 Years n=60 Participants Participants aged 18 to 60 years received one 0.5-mL dose of Fluzone Quadrivalent influenza vaccine, intramuscularly, at Day 0.	Fluzone Quadrivalent Influenza Vaccine: 61 Years or Older n=60 Participants Participants aged 61 years or older received one 0.5-mL dose of Fluzone Quadrivalent influenza vaccine, intramuscularly, at Day 0.
Number of Participants With Seroconversion or Significant Increase to Influenza Vaccine Antigens B Yamagata	51 Participants	47 Participants
Number of Participants With Seroconversion or Significant Increase to Influenza Vaccine Antigens A/H1N1	52 Participants	52 Participants
Number of Participants With Seroconversion or Significant Increase to Influenza Vaccine Antigens A/H3N2	48 Participants	52 Participants
Number of Participants With Seroconversion or Significant Increase to Influenza Vaccine Antigens B Victoria	54 Participants	55 Participants

PRIMARY outcome

Timeframe: Within 7 days after vaccination

Population: Analysis was performed on the safety analysis set.

A solicited reaction is an adverse event (AE) that is pre-listed in the electronic case report form (eCRF) and considered to be related to vaccination. Solicited injection site reactions: Pain (Grade 1: no interference with activity, Grade 2: some interference with activity, Grade 3: significantly prevent daily activity), erythema, swelling, induration, and ecchymosis (Grade 1: \>=25 mm to \<= 50 mm, Grade 2: \>=51 to \<=100 mm, Grade 3: \> 100 mm). Solicited systemic reactions: Fever (Grade 1: \>=38.0 degree Celsius (°C) to \<=38.4°C, Grade 2: \>=38.5°C to \<=38.9 °C, Grade 3: \>= 39°C), headache, malaise, myalgia, and shivering (Grade 1: no interference with activity, Grade 2: some interference with activity, Grade 3: significantly prevent daily activity). Number of participants with any of the Grade 1, 2 or 3 solicited injection-site and systemic reactions and Grade 3 solicited injection-site and systemic reactions were reported.

Outcome measures

Outcome measures
Measure	Fluzone Quadrivalent Influenza Vaccine: 18 to 60 Years n=60 Participants Participants aged 18 to 60 years received one 0.5-mL dose of Fluzone Quadrivalent influenza vaccine, intramuscularly, at Day 0.	Fluzone Quadrivalent Influenza Vaccine: 61 Years or Older n=60 Participants Participants aged 61 years or older received one 0.5-mL dose of Fluzone Quadrivalent influenza vaccine, intramuscularly, at Day 0.
Number of Participants Reporting Solicited Injection Site and Systemic Reactions Any Pain	19 Participants	14 Participants
Number of Participants Reporting Solicited Injection Site and Systemic Reactions Grade 3 Pain	0 Participants	0 Participants
Number of Participants Reporting Solicited Injection Site and Systemic Reactions Any Erythema	0 Participants	0 Participants
Number of Participants Reporting Solicited Injection Site and Systemic Reactions Grade 3 Erythema	0 Participants	0 Participants
Number of Participants Reporting Solicited Injection Site and Systemic Reactions Any Swelling	0 Participants	1 Participants
Number of Participants Reporting Solicited Injection Site and Systemic Reactions Grade 3 Swelling	0 Participants	0 Participants
Number of Participants Reporting Solicited Injection Site and Systemic Reactions Any Induration	1 Participants	1 Participants
Number of Participants Reporting Solicited Injection Site and Systemic Reactions Grade 3 Induration	0 Participants	0 Participants
Number of Participants Reporting Solicited Injection Site and Systemic Reactions Any Ecchymosis	0 Participants	0 Participants
Number of Participants Reporting Solicited Injection Site and Systemic Reactions Grade 3 Ecchymosis	0 Participants	0 Participants
Number of Participants Reporting Solicited Injection Site and Systemic Reactions Any Fever	1 Participants	1 Participants
Number of Participants Reporting Solicited Injection Site and Systemic Reactions Grade 3 Fever	1 Participants	1 Participants
Number of Participants Reporting Solicited Injection Site and Systemic Reactions Any Headache	8 Participants	3 Participants
Number of Participants Reporting Solicited Injection Site and Systemic Reactions Grade 3 Headache	0 Participants	0 Participants
Number of Participants Reporting Solicited Injection Site and Systemic Reactions Any Malaise	8 Participants	2 Participants
Number of Participants Reporting Solicited Injection Site and Systemic Reactions Grade 3 Malaise	0 Participants	0 Participants
Number of Participants Reporting Solicited Injection Site and Systemic Reactions Any Myalgia	6 Participants	4 Participants
Number of Participants Reporting Solicited Injection Site and Systemic Reactions Grade 3 Myalgia	0 Participants	0 Participants
Number of Participants Reporting Solicited Injection Site and Systemic Reactions Any Shivering	2 Participants	1 Participants
Number of Participants Reporting Solicited Injection Site and Systemic Reactions Grade 3 Shivering	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Within 3 days after vaccination

Population: Analysis was performed on the safety analysis set.

Solicited reactions listed in the CHMP note for guidance included: injection site induration \>= 50 mm for at least 4 consecutive days , injection site ecchymosis, temperature \> 38.0°C for at least one day, malaise, and shivering.

Outcome measures

Outcome measures
Measure	Fluzone Quadrivalent Influenza Vaccine: 18 to 60 Years n=60 Participants Participants aged 18 to 60 years received one 0.5-mL dose of Fluzone Quadrivalent influenza vaccine, intramuscularly, at Day 0.	Fluzone Quadrivalent Influenza Vaccine: 61 Years or Older n=60 Participants Participants aged 61 years or older received one 0.5-mL dose of Fluzone Quadrivalent influenza vaccine, intramuscularly, at Day 0.
Number of Participants Reporting Solicited Reactions Listed in the Committee for Medicinal Products for Human Use (CHMP) Note for Guidance Injection site induration	0 Participants	0 Participants
Number of Participants Reporting Solicited Reactions Listed in the Committee for Medicinal Products for Human Use (CHMP) Note for Guidance Injection site ecchymosis	0 Participants	0 Participants
Number of Participants Reporting Solicited Reactions Listed in the Committee for Medicinal Products for Human Use (CHMP) Note for Guidance Temperature	0 Participants	1 Participants
Number of Participants Reporting Solicited Reactions Listed in the Committee for Medicinal Products for Human Use (CHMP) Note for Guidance Malaise	7 Participants	2 Participants
Number of Participants Reporting Solicited Reactions Listed in the Committee for Medicinal Products for Human Use (CHMP) Note for Guidance Shivering	2 Participants	1 Participants

Adverse Events

Fluzone Quadrivalent Influenza Vaccine: 18 to 60 Years

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

Fluzone Quadrivalent Influenza Vaccine: 61 Years or Older

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Fluzone Quadrivalent Influenza Vaccine: 18 to 60 Years n=60 participants at risk Participants aged 18 to 60 years received one 0.5-mL dose of Fluzone Quadrivalent influenza vaccine, intramuscularly, at Day 0.	Fluzone Quadrivalent Influenza Vaccine: 61 Years or Older n=60 participants at risk Participants aged 61 years or older received one 0.5-mL dose of Fluzone Quadrivalent influenza vaccine, intramuscularly, at Day 0.
General disorders Injection Site Pain	31.7% 19/60 • Number of events 19 • AE data were collected from Day 0 (post-vaccination) up to Day 28 post vaccination . A solicited reaction is an AE that is prelisted in the eCRF and considered to be related to vaccination. A solicited reaction is therefore an adverse drug reaction (ADR) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the eCRF. An unsolicited AE is an observed AE that does not fulfill the conditions prelisted in the eCRF in terms of symptom and/or onset post-vaccination.	23.3% 14/60 • Number of events 14 • AE data were collected from Day 0 (post-vaccination) up to Day 28 post vaccination . A solicited reaction is an AE that is prelisted in the eCRF and considered to be related to vaccination. A solicited reaction is therefore an adverse drug reaction (ADR) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the eCRF. An unsolicited AE is an observed AE that does not fulfill the conditions prelisted in the eCRF in terms of symptom and/or onset post-vaccination.
General disorders Malaise	13.3% 8/60 • Number of events 8 • AE data were collected from Day 0 (post-vaccination) up to Day 28 post vaccination . A solicited reaction is an AE that is prelisted in the eCRF and considered to be related to vaccination. A solicited reaction is therefore an adverse drug reaction (ADR) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the eCRF. An unsolicited AE is an observed AE that does not fulfill the conditions prelisted in the eCRF in terms of symptom and/or onset post-vaccination.	3.3% 2/60 • Number of events 2 • AE data were collected from Day 0 (post-vaccination) up to Day 28 post vaccination . A solicited reaction is an AE that is prelisted in the eCRF and considered to be related to vaccination. A solicited reaction is therefore an adverse drug reaction (ADR) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the eCRF. An unsolicited AE is an observed AE that does not fulfill the conditions prelisted in the eCRF in terms of symptom and/or onset post-vaccination.
Musculoskeletal and connective tissue disorders Myalgia	10.0% 6/60 • Number of events 6 • AE data were collected from Day 0 (post-vaccination) up to Day 28 post vaccination . A solicited reaction is an AE that is prelisted in the eCRF and considered to be related to vaccination. A solicited reaction is therefore an adverse drug reaction (ADR) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the eCRF. An unsolicited AE is an observed AE that does not fulfill the conditions prelisted in the eCRF in terms of symptom and/or onset post-vaccination.	6.7% 4/60 • Number of events 4 • AE data were collected from Day 0 (post-vaccination) up to Day 28 post vaccination . A solicited reaction is an AE that is prelisted in the eCRF and considered to be related to vaccination. A solicited reaction is therefore an adverse drug reaction (ADR) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the eCRF. An unsolicited AE is an observed AE that does not fulfill the conditions prelisted in the eCRF in terms of symptom and/or onset post-vaccination.
Nervous system disorders Headache	13.3% 8/60 • Number of events 8 • AE data were collected from Day 0 (post-vaccination) up to Day 28 post vaccination . A solicited reaction is an AE that is prelisted in the eCRF and considered to be related to vaccination. A solicited reaction is therefore an adverse drug reaction (ADR) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the eCRF. An unsolicited AE is an observed AE that does not fulfill the conditions prelisted in the eCRF in terms of symptom and/or onset post-vaccination.	5.0% 3/60 • Number of events 3 • AE data were collected from Day 0 (post-vaccination) up to Day 28 post vaccination . A solicited reaction is an AE that is prelisted in the eCRF and considered to be related to vaccination. A solicited reaction is therefore an adverse drug reaction (ADR) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the eCRF. An unsolicited AE is an observed AE that does not fulfill the conditions prelisted in the eCRF in terms of symptom and/or onset post-vaccination.

Additional Information

Medical Director

Sanofi Pasteur Inc.

Phone: 800-633-1610 ext 1#

Email: [email protected]

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