NCT03308825

Safety and Immunogenicity of Fluzone® Quadrivalent and Fluzone® High-Dose, Influenza Vaccines

Completed Phase 4 Results posted Last updated 29 March 2022

What this trial tests

Phase 4 trial testing Fluzone Quadrivalent vaccine in Influenza in 240 participants. Completed in 22 November 2017.

Timeline

11 September 2017

Primary endpoint
22 November 2017

22 November 2017

Quick facts

Lead sponsor	Sanofi Pasteur, a Sanofi Company
Phase	Phase 4
Status	Completed
Study type	INTERVENTIONAL
Allocation	non randomized
Design	parallel
Masking	none
Primary purpose	prevention
Enrollment	240
Start date	11 September 2017
Primary completion	22 November 2017
Estimated completion	22 November 2017
Sites	3 locations across United States

Drugs / interventions tested

• Fluzone Quadrivalent vaccine
• Fluzone Quadrivalent vaccine
• Fluzone High-Dose vaccine — full drug profile →

Conditions studied

• Influenza — all drugs for Influenza →
• Flu — all drugs for Flu →

Sponsor

Sanofi Pasteur, a Sanofi Company — full company profile →

Who can join

6 Months and older, any sex, with Influenza or Flu. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Participants Reporting Solicited Injection Site (Tenderness/Pain, Erythema, Swelling) and Systemic Reactions (Fever, Vomiting, Crying Abnormal, Drowsiness, Appetite Lost, Irritability): Group 1 (6 to < 36 Months) Primary · Within 7 days after any vaccination

Solicited injection site reactions: Pain, Erythema and Swelling (Grade 3: Pain: cries when injected limb moved/ limb movement reduced, erythema and swelling \>= 50 mm). Solicited systemic reactions: Fever, vomiting, abnormal crying, drowsiness, appetite lost, Irritability (Grade 3: Fever: \>= 39.5 degrees Celsius \[103.1 degree Fahrenheit {°F}\], vomiting \>= six episodes per 24 hours, abnormal crying : \> 3 hours, drowsiness: sleeping most of the time or difficult to wake up, appetite lost: refuses \>= 3 feeds/meals or refuses most feeds/meals, Irritability: Inconsolable).

Tenderness

Group	Value	95% CI
Group 1: 6 to < 36 Months	16

Tenderness : Grade 3

Group	Value	95% CI
Group 1: 6 to < 36 Months	1

Erythema

Group	Value	95% CI
Group 1: 6 to < 36 Months	4

Erythema : Grade 3

Group	Value	95% CI
Group 1: 6 to < 36 Months	0

Swelling

Group	Value	95% CI
Group 1: 6 to < 36 Months	2

Swelling : Grade 3

Group	Value	95% CI
Group 1: 6 to < 36 Months	0

Fever

Group	Value	95% CI
Group 1: 6 to < 36 Months	6

Fever : Grade 3

Group	Value	95% CI
Group 1: 6 to < 36 Months	0

Number of Participants Reporting Solicited Injection Site (Pain, Erythema, Swelling) and Systemic Reactions(Fever, Headache, Malaise, Myalgia): Group 2 (3 to < 9 Years), Group 3 (18 to < 65 Years) and Group 4(=< 65 Years) Primary · Within 7 days after any vaccination

Solicited injection site reactions: Pain (Group 2: Grade 3: Incapacitating; Group 3 and 4: Grade 3: significant; prevents daily activity), erythema \& swelling (Group 2: Grade 3: \>= 50 mm, Group 3 and 4: Grade 3: \> 100 mm). Solicited systemic reactions: Fever (Grade 3: \>= 39.0 degrees Celsius \[102.2°F\]), headache, malaise \& myalgia (Grade 3: significant interference with daily activities).

Pain

Group	Value	95% CI
Group 2: 3 to < 9 Years	25
Group 3: 18 to < 65 Years	27
Group 4: >= 65 Years	20

Pain: Grade 3

Group	Value	95% CI
Group 2: 3 to < 9 Years	1
Group 3: 18 to < 65 Years	1
Group 4: >= 65 Years	0

Erythema

Group	Value	95% CI
Group 2: 3 to < 9 Years	9
Group 3: 18 to < 65 Years	0
Group 4: >= 65 Years	3

Erythema : Grade 3

Group	Value	95% CI
Group 2: 3 to < 9 Years	3
Group 3: 18 to < 65 Years	0
Group 4: >= 65 Years	0

Swelling

Group	Value	95% CI
Group 2: 3 to < 9 Years	11
Group 3: 18 to < 65 Years	1
Group 4: >= 65 Years	2

Swelling : Grade 3

Group	Value	95% CI
Group 2: 3 to < 9 Years	2
Group 3: 18 to < 65 Years	0
Group 4: >= 65 Years	0

Fever

Group	Value	95% CI
Group 2: 3 to < 9 Years	1
Group 3: 18 to < 65 Years	0
Group 4: >= 65 Years	1

Fever : Grade 3

Group	Value	95% CI
Group 2: 3 to < 9 Years	1
Group 3: 18 to < 65 Years	0
Group 4: >= 65 Years	1

Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies in Children: Group 1 (6 to < 36 Months) and Group 2 (3 to < 9 Years) Primary · Day 0 (pre-vaccination) and Day 28 (post-vaccination)

Anti-influenza antibodies were measured using the hemagglutination inhibition (HAI) assay for 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage.

Pre-Vaccination: A/H1N1

Group	Value	95% CI
Group 1: 6 to < 36 Months	19.9	11.9 – 33.1
Group 2: 3 to < 9 Years	306	198 – 473

Pre-Vaccination: A/H3N2

Group	Value	95% CI
Group 1: 6 to < 36 Months	49.7	27.7 – 89.2
Group 2: 3 to < 9 Years	415	253 – 681

Pre-Vaccination: B Victoria

Group	Value	95% CI
Group 1: 6 to < 36 Months	32.0	19.7 – 52.0
Group 2: 3 to < 9 Years	180	112 – 290

Pre-Vaccination: B Yamagata

Group	Value	95% CI
Group 1: 6 to < 36 Months	43.5	27.6 – 68.5
Group 2: 3 to < 9 Years	334	219 – 510

Post-Final Vaccination: A/H1N1

Group	Value	95% CI
Group 1: 6 to < 36 Months	450	301 – 671
Group 2: 3 to < 9 Years	1606	1198 – 2153

Post-Final Vaccination: A/H3N2

Group	Value	95% CI
Group 1: 6 to < 36 Months	568	336 – 958
Group 2: 3 to < 9 Years	2370	1712 – 3282

Post-Final Vaccination: B Victoria

Group	Value	95% CI
Group 1: 6 to < 36 Months	481	313 – 738
Group 2: 3 to < 9 Years	1668	1142 – 2436

Post-Final Vaccination: B Yamagata

Group	Value	95% CI
Group 1: 6 to < 36 Months	698	465 – 1047
Group 2: 3 to < 9 Years	2187	1610 – 2971

GMTs of Influenza Vaccine Antibodies in Adults: Group 3 (18 to < 65 Years) and Group 4 (>= 65 Years) Primary · Day 0 (pre-vaccination) and Day 21 (post-vaccination)

Anti-influenza antibodies were measured using the HAI assay for each of the following 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage (for Group 3) and for 3 strains: H1N1, H3N2, and B Victoria lineage (for Group 4).

Pre-Vaccination: A/H1N1

Group	Value	95% CI
Group 3: 18 to < 65 Years	165	110 – 248
Group 4: >= 65 Years	74.6	52.3 – 106

Pre-Vaccination: A/H3N2

Group	Value	95% CI
Group 3: 18 to < 65 Years	231	150 – 356
Group 4: >= 65 Years	194	130 – 291

Pre-Vaccination: B Victoria

Group	Value	95% CI
Group 3: 18 to < 65 Years	276	185 – 412
Group 4: >= 65 Years	215	151 – 305

Pre-Vaccination: B Yamagata

Group	Value	95% CI
Group 3: 18 to < 65 Years	425	308 – 587

Post-Final Vaccination: A/H1N1

Group	Value	95% CI
Group 3: 18 to < 65 Years	756	539 – 1062
Group 4: >= 65 Years	393	275 – 561

Post-Final Vaccination: A/H3N2

Group	Value	95% CI
Group 3: 18 to < 65 Years	1128	791 – 1610
Group 4: >= 65 Years	864	612 – 1218

Post-Final Vaccination: B Victoria

Group	Value	95% CI
Group 3: 18 to < 65 Years	1117	853 – 1463
Group 4: >= 65 Years	644	465 – 892

Post-Final Vaccination: B Yamagata

Group	Value	95% CI
Group 3: 18 to < 65 Years	1312	1010 – 1704

GMT Ratios (GMTRs) of Influenza Vaccine Antibodies in Children: Group 1 (6 to < 36 Months) and Group 2 (3 to < 9 Years) Primary · Day 0 (pre-vaccination) and Day 28 (post-final vaccination)

GMTRs are the geometric means of the individual post-final vaccination/pre-vaccination titer ratios for each of the following 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage, measured using the HAI assay.

A/H1N1

Group	Value	95% CI
Group 1: 6 to < 36 Months	17.6	12.1 – 25.6
Group 2: 3 to < 9 Years	5.05	3.56 – 7.16

A/H3N2

Group	Value	95% CI
Group 1: 6 to < 36 Months	10.8	7.54 – 15.4
Group 2: 3 to < 9 Years	5.54	3.67 – 8.37

B Victoria

Group	Value	95% CI
Group 1: 6 to < 36 Months	13.1	8.86 – 19.3
Group 2: 3 to < 9 Years	9.02	6.06 – 13.4

B Yamagata

Group	Value	95% CI
Group 1: 6 to < 36 Months	14.0	9.44 – 20.8
Group 2: 3 to < 9 Years	6.46	4.70 – 8.88

GMTRs of Influenza Vaccine Antibodies in Adults: Group 3 (18 to < 65 Years) and Group 4 (>= 65 Years) Primary · Day 0 (pre-vaccination) and Day 21 (post-vaccination)

GMTRs are the geometric means of the individual post-final vaccination/pre-vaccination titer ratios for each of the following 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage (for Group 3) and for 3 strains: H1N1, H3N2, and B Victoria lineage (for Group 4), measured using the HAI assay.

A/H1N1

Group	Value	95% CI
Group 3: 18 to < 65 Years	4.31	2.91 – 6.40
Group 4: Adults >= 65 Years	5.15	3.50 – 7.57

A/H3N2

Group	Value	95% CI
Group 3: 18 to < 65 Years	4.44	2.88 – 6.85
Group 4: Adults >= 65 Years	4.45	3.09 – 6.40

B Victoria

Group	Value	95% CI
Group 3: 18 to < 65 Years	4.05	2.55 – 6.43
Group 4: Adults >= 65 Years	2.96	2.26 – 3.88

B Yamagata

Group	Value	95% CI
Group 3: 18 to < 65 Years	3.09	2.16 – 4.42

Number of Participants With Seroprotection to Influenza Vaccine Antigens: Group 1 (6 to < 36 Months) and Group 2 (3 to < 9 Years) Primary · Day 0 (pre-vaccination) and Day 28 (post-vaccination)

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

Pre-Vaccination: A/H1N1

Group	Value	95% CI
Group 1: 6 to < 36 Months	15
Group 2: 3 to < 9 Years	48

Pre-Vaccination: A/H3N2

Group	Value	95% CI
Group 1: 6 to < 36 Months	24
Group 2: 3 to < 9 Years	46

Pre-Vaccination: B Victoria

Group	Value	95% CI
Group 1: 6 to < 36 Months	21
Group 2: 3 to < 9 Years	44

Pre-Vaccination: B Yamagata

Group	Value	95% CI
Group 1: 6 to < 36 Months	31
Group 2: 3 to < 9 Years	50

Post-Final Vaccination: A/H1N1

Group	Value	95% CI
Group 1: 6 to < 36 Months	51
Group 2: 3 to < 9 Years	54

Post-Final Vaccination: A/H3N2

Group	Value	95% CI
Group 1: 6 to < 36 Months	50
Group 2: 3 to < 9 Years	54

Post-Final Vaccination: B Victoria

Group	Value	95% CI
Group 1: 6 to < 36 Months	50
Group 2: 3 to < 9 Years	54

Post-Final Vaccination: B Yamagata

Group	Value	95% CI
Group 1: 6 to < 36 Months	50
Group 2: 3 to < 9 Years	55

Number of Participants With Seroprotection to Influenza Vaccine Antigens: Group 3 (18 to < 65 Years) and Group 4 (>= 65 Years) Primary · Day 0 (pre-vaccination) and Day 21 (post-vaccination)

Anti-influenza antibodies were measured using the HAI assay for each of the following 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage (for Group 3) and for 3 strains: H1N1, H3N2, and B Victoria lineage (for Group 4). Seroprotection was defined as antibody titer \>= 40 (1/ dilution) at pre-vaccination or at post-final vaccination.

Pre-Vaccination: A/H1N1

Group	Value	95% CI
Group 3: 18 to < 65 Years	45
Group 4: >= 65 Years	40

Pre-Vaccination: A/H3N2

Group	Value	95% CI
Group 3: 18 to < 65 Years	48
Group 4: >= 65 Years	49

Pre-Vaccination: B Victoria

Group	Value	95% CI
Group 3: 18 to < 65 Years	48
Group 4: >= 65 Years	55

Pre-Vaccination: B Yamagata

Group	Value	95% CI
Group 3: 18 to < 65 Years	54

Post-Final Vaccination: A/H1N1

Group	Value	95% CI
Group 3: 18 to < 65 Years	55
Group 4: >= 65 Years	57

Post-Final Vaccination: A/H3N2

Group	Value	95% CI
Group 3: 18 to < 65 Years	55
Group 4: >= 65 Years	59

Post-Final Vaccination: B Victoria

Group	Value	95% CI
Group 3: 18 to < 65 Years	56
Group 4: >= 65 Years	58

Post-Final Vaccination: B Yamagata

Group	Value	95% CI
Group 3: 18 to < 65 Years	56

Number of Participants With Seroconversion to Influenza Vaccine Antigens: Group 1 (6 to < 36 Months) and Group 2 (3 to < 9 Years) Primary · Day 0 (pre-vaccination) and Day 28 (post-final vaccination)

Anti-influenza antibodies were measured using the HAI assay for 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage. Seroconversion was defined as either a pre-vaccination HAI titer \< 1:10 and a post-final vaccination titer \>= 1:40 or a pre-vaccination titer \>= 1:10 and at least a 4-fold increase in post-final vaccination titer.

A/H1N1

Group	Value	95% CI
Group 1: 6 to < 36 Months	45
Group 2: 3 to < 9 Years	28

A/H3N2

Group	Value	95% CI
Group 1: 6 to < 36 Months	42
Group 2: 3 to < 9 Years	30

B Victoria

Group	Value	95% CI
Group 1: 6 to < 36 Months	44
Group 2: 3 to < 9 Years	39

B Yamagata

Group	Value	95% CI
Group 1: 6 to < 36 Months	46
Group 2: 3 to < 9 Years	36

Number of Participants With Seroconversion to Influenza Vaccine Antigens: Group 3 (18 to < 65 Years) and Group 4 (>= 65 Years) Primary · Day 0 (pre-vaccination) and Day 21 (post-vaccination)

Anti-influenza antibodies were measured using the HAI assay for each of the following 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage (for Group 3) and for 3 strains: H1N1, H3N2, and B Victoria lineage (for Group 4). Seroconversion was defined as either a pre-vaccination HAI titer \< 1:10 and a post-final vaccination titer \>= 1:40 or a pre-vaccination titer \>= 1:10 and at least a 4-fold increase in post-final vaccination titer.

A/H1N1

Group	Value	95% CI
Group 3: 18 to < 65 Years	26
Group 4: >= 65 Years	33

A/H3N2

Group	Value	95% CI
Group 3: 18 to < 65 Years	22
Group 4: >= 65 Years	33

B Victoria

Group	Value	95% CI
Group 3: 18 to < 65 Years	19
Group 4: >= 65 Years	18

B Yamagata

Group	Value	95% CI
Group 3: 18 to < 65 Years	22

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 56 for Groups 1 and 2; up to Day 21 for Groups 3 and 4.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Group 1: 6 to < 36 Months

Serious: 0/59 (0%)

Deaths: 0/59

Group 2: 3 to < 9 Years

Serious: 0/61 (0%)

Deaths: 0/61

Group 3: 18 to < 65 Years

Serious: 2/60 (3%)

Deaths: 0/60

Group 4: >= 65 Years

Serious: 0/60 (0%)

Deaths: 0/60

Serious adverse events (3 terms)

Reaction	System	Group 1: 6 to < 36 Months	Group 2: 3 to < 9 Years	Group 3: 18 to < 65 Years	Group 4: >= 65 Years
Abortion Spontaneous	Pregnancy, puerperium and perinatal conditions	—	—	—	—
Anxiety	Psychiatric disorders	—	—	—	—
Depression	Psychiatric disorders	—	—	—	—

Other adverse events (13 terms — click to expand)

Reaction	System	Group 1: 6 to < 36 Months	Group 2: 3 to < 9 Years	Group 3: 18 to < 65 Years	Group 4: >= 65 Years
Injection Site Pain	General disorders	—	—	—	—
Myalgia	Musculoskeletal and connective tissue disorders	—	—	—	—
Irritability	Psychiatric disorders	—	—	—	—
Injection Site Swelling	General disorders	—	—	—	—
Somnolence	Nervous system disorders	—	—	—	—
Crying	General disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—
Injection Site Erythema	General disorders	—	—	—	—
Malaise	General disorders	—	—	—	—
Pyrexia	General disorders	—	—	—	—
Decreased Appetite	Metabolism and nutrition disorders	—	—	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—	—

Most-reported serious reactions: Abortion Spontaneous, Anxiety, Depression.

Data from ClinicalTrials.gov NCT03308825 adverse events section.

Sponsor's own description

The aim of the study was to describe the safety and immunogenicity of the 2017-2018 formulation of Fluzone Quadrivalent vaccine in children 6 months to \< 9 years of age, and in adults 18 to \< 65 years of age, and to describe the safety and immunogenicity of the 2017-2018 formulation of Fluzone High-Dose vaccine in adults ≥ 65 years of age.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.