Safety and Immunogenicity of Different Dosages of High-Dose Quadrivalent Influenza Vaccine in Children 6 Months to 17 Years of Age

Sanofi Pasteur, a Sanofi Company665 enrolled

Overview

The objectives of this study were: * To describe the safety of each dosage of high-dose quadrivalent influenza vaccine (QIV-HD) used in the study during the 28 days following each vaccination, and serious adverse events (including adverse events of special interest throughout the study). * To describe the antibody response induced by each dosage of QIV-HD used in the study compared with unadjuvanted standard-dose quadrivalent influenza vaccine (QIV-SD) by hemagglutination inhibition (HAI) measurement method. * To describe the antibody response induced by each dosage of QIV-HD used in the study compared with unadjuvanted QIV-SD by virus seroneutralization (SN) measurement method. * To describe the antibody response induced by the highest acceptable dosage of QIV-HD compared with adjuvanted trivalent influenza vaccine (TIV) by HAI and virus SN measurement methods.

Study duration per participant was approximately 180 days for participants who received one dose of vaccine and 208 days for participants who received two doses of vaccine.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Enrollment

665

Conditions

Influenza

Interventions

Eligibility

Sex: ALLMin age: 6 MonthsMax age: 17 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion criteria : * Aged 6 months to 17 years on the day of inclusion. * Assent form was signed and dated by the participant (7 to 17 years of age) and informed consent form was signed and dated by the parent(s) or guardian(s) and by an independent witness, if required by local regulations. * Participant and parent/guardian were able to attend all scheduled visits and complied with all study procedures. * For participants aged \<24 months: Born at full term of pregnancy (greater than or equal to \[\>=\] 37 weeks) and/or with a birth weight \>=2.5 kilogram. 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 until at least 4 weeks after vaccination. To be considered of non-childbearing potential, a female must be pre-menarche. * Participation at the time of study enrollment (or in the 4 weeks 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. * Receipt of any vaccine in the 30 days preceding the first study vaccination, or planned receipt of any vaccine before Visit 3 for participants receiving 1 dose of influenza vaccine or Visit 5 for participants receiving 2 doses of influenza vaccine. * For previously influenza vaccinated participants: Previous vaccination against influenza in the preceding 6 months with either the study vaccine or another vaccine. * For previously influenza unvaccinated participants: Any influenza vaccination (from birth to the day of inclusion) with either the study vaccine or another influenza vaccine. * For previously influenza unvaccinated participants: Any previous laboratory confirmed influenza infection (from birth to the day of inclusion) * Receipt of immune globulins, blood or blood-derived products in the past 3 months. * Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months). * Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the study or to a vaccine containing any of the same substances. * Thrombocytopenia or bleeding disorder, contraindicating IM vaccination based on Investigator's judgement. * 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 vaccination or febrile illness (temperature \>=38.0°Celsius \[\>=100.4°Fahrenheit\]). A prospective participant should not be included in the study until the condition had resolved or the febrile event had subsided. * Identified as an immediate family member (i.e., spouse, natural or adopted child, grandchild, nephew, or niece) of the Investigator or employee with direct involvement in the proposed study. * 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 development delay (at the discretion of the Investigator), neurologic disorder, or seizure disorder. * Known seropositivity for hepatitis B or hepatitis C. The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Locations (16)

Investigational Site Number 8400004

San Diego, California, United States

Investigational Site Number 8400001

Miami, Florida, United States

Investigational Site Number 8400002

Atlanta, Georgia, United States

Investigational Site Number 8400013

El Dorado, Kansas, United States

Investigational Site Number 8400015

Newton, Kansas, United States

Investigational Site Number 8400009

Wichita, Kansas, United States

Investigational Site Number 8400007

Metairie, Louisiana, United States

Investigational Site Number 8400010

Las Vegas, Nevada, United States

Investigational Site Number 8400011

Warwick, Rhode Island, United States

Investigational Site Number 8400003

Salt Lake City, Utah, United States

...and 6 more locations

Outcomes

Primary Outcomes

Number of Participants With Immediate Unsolicited Adverse Events (AEs) After Any Vaccination

An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report book (CRB) in terms of diagnosis and/or onset window post-vaccination. Unsolicited AEs includes both serious (SAEs) and non-serious unsolicited AEs. An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. All participants were observed for 30 minutes after vaccination, and any unsolicited systemic AEs occurred during that time were recorded as immediate unsolicited AEs in the CRB.

Time frame: Within 30 minutes after any vaccination

Number of Participants With Unsolicited Adverse Events After Any Vaccination

An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the CRB in terms of diagnosis and/or onset window post-vaccination. Unsolicited AEs included both serious and non-serious unsolicited AEs. An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. Adverse reactions (ARs) were AEs related to vaccination. An injection site reaction was an AR at and around the injection site. Systemic AEs were all AEs that were not injection or administration site reactions.

Time frame: Within 28 days after any vaccination

Number of Participants With Serious Adverse Events (SAEs) After Any Vaccination

An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. An SAE which caused death of the participant was considered as fatal SAE. Adverse events of special interest (AESIs) were defined as SAEs which included new onset of Guillain-Barré syndrome, encephalitis/myelitis (including transverse myelitis), Bell's palsy, convulsions, optic neuritis, and brachial neuritis.

Time frame: From Day 0 up to 6 months (i.e. 180 days) post last vaccination

Number of Participants Achieving Seroconversion Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine

Anti-influenza antibodies were measured by hemagglutination inhibition (HAI) assay for strains A/H1N1, A/H3N2, B/Victoria and B/Yamagata lineage. Seroconversion: defined as either HAI titer \<10(1/dilution) at Day 0 and post-vaccination titer greater than or equal to (\>=)40(1/dilution) at Day 28, or HAI titer \>=10(1/dilution) at Day 0 and \>=4-fold increase in HAI titer (1/dilution) at Day 28. Data for this Outcome Measure (OM) was planned to be collected and reported for dose level (QIV-HD 30μg and 45μg) matched separate groups for QIV-SD (Groups 4a, 4b and 4c), instead of pooled QIV-SD arm. Due to complex study design and analysis of doses and age groups, QIV-SD group participants, who matched to participants in QIV-HD 30μg and 45μg dose formulations groups (who were 9 through 17 years old and shared matching age group with QIV-SD control group), included in Groups 4a, 4b and 4c in this OM might be counted in more than once in QIV-SD arms for different dose levels, as applicable.