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

Influenza Clinical Trial

Official title:

Safety and Immunogenicity of Fluzone® Quadrivalent and Fluzone® High-Dose, Influenza Vaccines, 2017-2018 Formulations

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03308825
• Other study ID #: GRC73
• Secondary ID: U1111-1183-5816
• Status: Completed
• Phase: Phase 4
• Start date: September 11, 2017
• Est. completion date: November 22, 2017

Study information

• Verified date: March 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

All participants received 1 intramuscular dose of their assigned vaccine during Visit 1. For participants, for whom 2 doses of influenza vaccine were recommended per Advisory Committee on Immunization Practices (ACIP) guidance, a second dose of the same volume as the first dose was administered during Visit 2 (28 days after Visit 1). Solicited adverse reaction (AR) information was collected for 7 days following each vaccination. Unsolicited non-serious adverse event (AE) and serious adverse event (SAE) information was collected from Visit 1 to Visit 2 or from Visit 1 to Visit 3 for those participants receiving 2 doses of study vaccine.

Immunogenicity was evaluated in all participants prior to vaccination on Day 0 (Visit 1) and after the final vaccination (Day 28 post-final vaccination for participants 6 months to < 9 years of age and Day 21 post-vaccination for participants ≥ 18 years of age).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 240
• Est. completion date: November 22, 2017
• Est. primary completion date: November 22, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Months and older

Eligibility

Inclusion Criteria:

• Aged 6 months to < 9 years or = 18 years on the day of first study vaccination (study product administration).

• For participants 6 to < 12 months of age, born at full term of pregnancy (= 37 weeks) and with a birth weight = 2.5 kg (5.5 lbs).

• Informed consent form has been signed and dated by participants = 18 years of age.

• Assent form was signed and dated by participants 7 to < 9 years of age, and informed consent form has been signed and dated by parent(s) or guardian(s) for participants 6 months to < 9 years of age.

• Participant and parent/guardian (of participants 6 months to < 9 years of age) were able to attend all scheduled visits and to comply with all study procedures.

Exclusion Criteria:

• Participant was pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination and until at least 4 weeks after vaccination. To be considered of non-childbearing potential, a female must be pre-menarche, or post- menopausal for at least 1 year, or surgically sterile.

• Participation at the time of study enrollment (or in the 30 days preceding the first study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure. Note: Participants may be considered eligible for enrollment if no intervention for the other study occurred within the 30 days prior to the first study vaccination and none are planned before the participant would complete safety surveillance for the present study.

• Receipt of any vaccine in the 30 days preceding the first study vaccination, or planned receipt of any vaccine before Visit 2 for participants receiving 1 dose of influenza vaccine or Visit 3 for participants receiving 2 doses of influenza vaccine.

• Previous vaccination against influenza (in the 2017-2018 influenza season) with either study vaccine or another vaccine.

• Receipt of immune globulins, blood, or blood-derived products in the 3 months preceding planned inclusion.

• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the 6 months preceding planned inclusion; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the 3 months preceding planned inclusion).

• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to study vaccine or to a vaccine containing any of the same substances. Note: The list of vaccine components is included in the Prescribing Information for each study vaccine.

• Thrombocytopenia, which may be a contraindication for intramuscular vaccination, at the discretion of the Investigator.

• Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination.

• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.

• Current alcohol abuse or drug addiction.

• Chronic illness that, in the opinion of the Investigator, was at a stage where it might interfere with study conduct or completion.

• Moderate or severe acute illness/infection (according to Investigator judgment) on the day of planned vaccination or febrile illness (temperature = 100.4 degree Fahrenheit [°F] [38.0 degrees Celsius {°C}]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.

• Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study (participants = 18 years of age) or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study (all participants).

• History of serious adverse reaction to any influenza vaccine.

• Personal history of Guillain-Barré syndrome.

• Any condition that in the opinion of the Investigator would pose a health risk to the participant if enrolled or could interfere with the evaluation of the vaccine.

• Personal history of clinically significant developmental delay (at the discretion of the Investigator), neurologic disorder, or seizure disorder.

• Known seropositivity for human immunodeficiency virus, hepatitis B, or hepatitis C.

Related Conditions & MeSH terms

• Flu
• Influenza
• Influenza, Human

Intervention

Biological:
• Fluzone Quadrivalent vaccine
0.25 mL, Intramuscular
• Fluzone Quadrivalent vaccine
0.5 mL, Intramuscular
• Fluzone High-Dose vaccine
0.5 mL, Intramuscular

Locations

Country	Name	City	State
United States	Sanofi Pasteur Investigational Site 002	Bardstown	Kentucky
United States	Sanofi Pasteur Investigational Site 003	Council Bluffs	Iowa
United States	Sanofi Pasteur Investigational Site 001	Metairie	Louisiana

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi Pasteur, a Sanofi Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	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).	Within 7 days after any vaccination
Primary	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)	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).	Within 7 days after any vaccination
Primary	Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies in Children: Group 1 (6 to < 36 Months) and Group 2 (3 to < 9 Years)	Anti-influenza antibodies were measured using the hemagglutination inhibition (HAI) assay for 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage.	Day 0 (pre-vaccination) and Day 28 (post-vaccination)
Primary	GMTs of Influenza Vaccine Antibodies in Adults: Group 3 (18 to < 65 Years) and Group 4 (>= 65 Years)	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).	Day 0 (pre-vaccination) and Day 21 (post-vaccination)
Primary	GMT Ratios (GMTRs) of Influenza Vaccine Antibodies in Children: Group 1 (6 to < 36 Months) and Group 2 (3 to < 9 Years)	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.	Day 0 (pre-vaccination) and Day 28 (post-final vaccination)
Primary	GMTRs of Influenza Vaccine Antibodies in Adults: Group 3 (18 to < 65 Years) and Group 4 (>= 65 Years)	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.	Day 0 (pre-vaccination) and Day 21 (post-vaccination)
Primary	Number of Participants With Seroprotection to Influenza Vaccine Antigens: Group 1 (6 to < 36 Months) and Group 2 (3 to < 9 Years)	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.	Day 0 (pre-vaccination) and Day 28 (post-vaccination)
Primary	Number of Participants With Seroprotection to Influenza Vaccine Antigens: Group 3 (18 to < 65 Years) and Group 4 (>= 65 Years)	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.	Day 0 (pre-vaccination) and Day 21 (post-vaccination)
Primary	Number of Participants With Seroconversion to Influenza Vaccine Antigens: Group 1 (6 to < 36 Months) and Group 2 (3 to < 9 Years)	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.	Day 0 (pre-vaccination) and Day 28 (post-final vaccination)
Primary	Number of Participants With Seroconversion to Influenza Vaccine Antigens: Group 3 (18 to < 65 Years) and Group 4 (>= 65 Years)	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.	Day 0 (pre-vaccination) and Day 21 (post-vaccination)

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