Clinical trial NCT03698279: Safety and Immunogenicity of Different Dosages of High-Dose Quadrivalent Influenza Vaccine in Children 6 Months to 17 Years of Age
Official title: Safety and Immunogenicity of Different Dosages of High-Dose Quadrivalent Influenza Vaccine in Children 6 Months to 17 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2018-10-05
Enrollment: 665
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The study was divided into 13 groups and enrolled participants in 4 stages. The study used a stepwise age de-escalation and dose ascension design for children 6 months to less than (\<) 5 years of age.
Primary purpose: PREVENTION

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Immediate Unsolicited Adverse Events (AEs) After Any Vaccination
timeFrame: Within 30 minutes after any vaccination
measure: Number of Participants With Unsolicited Adverse Events After Any Vaccination
timeFrame: Within 28 days after any vaccination
measure: Number of Participants With Serious Adverse Events (SAEs) After Any Vaccination
timeFrame: From Day 0 up to 6 months (i.e. 180 days) post last vaccination
measure: 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
timeFrame: Day 28 post any vaccination
measure: Geometric Mean Titers (GMTs) of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine
timeFrame: Day 28 post any vaccination
measure: Geometric Mean Titer Ratios (GMTRs) of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine
timeFrame: Day 0 (pre-vaccination), Day 28 (post any vaccination)
measure: Number of Participants With Neutralization Antibody Titers >= 40 (1/Dilution) Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine
timeFrame: Day 28 post any vaccination
measure: Geometric Mean Titers of Influenza Antibodies (Measured by Seroneutralization [SN] Assay) Following Vaccination With Either High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine
timeFrame: Day 28 post any vaccination
measure: Geometric Mean Titers Ratio of Influenza Antibodies (Measured by Seroneutralization Assay) Following Vaccination With Either High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine
timeFrame: Day 0 (pre-vaccination), Day 28 (post any vaccination)
measure: Number of Participants With Neutralization Antibody Titers Above Pre-Defined Thresholds
timeFrame: Day 28 post any vaccination
measure: Number of Participants With Two-Fold and Four-Fold Increase in Neutralization Antibody Titer
timeFrame: Day 28 post any vaccination
measure: Number of Participants With Solicited Injection Site Reactions
timeFrame: Within 7 days after any vaccination
measure: Number of Participants With Solicited Systemic Reactions After Any Vaccination
timeFrame: Within 7 days after any vaccination
measure: Number of Participants With Solicited Systemic Reactions After Any Vaccination: Participants Aged >36 Months
timeFrame: Within 7 days after any vaccination
Secondary outcomes:
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Investigational Site Number 8400004
state: California
city: Miami
country: United States
facility: Investigational Site Number 8400001
state: Florida
city: Atlanta
country: United States
facility: Investigational Site Number 8400002
state: Georgia
city: El Dorado
country: United States
facility: Investigational Site Number 8400013
state: Kansas
city: Newton
country: United States
facility: Investigational Site Number 8400015
state: Kansas
city: Wichita
country: United States
facility: Investigational Site Number 8400009
state: Kansas
city: Metairie
country: United States
facility: Investigational Site Number 8400007
state: Louisiana
city: Las Vegas
country: United States
facility: Investigational Site Number 8400010
state: Nevada
city: Warwick
country: United States
facility: Investigational Site Number 8400011
state: Rhode Island
city: Salt Lake City
country: United States
facility: Investigational Site Number 8400003
state: Utah
city: Salt Lake City
country: United States
facility: Investigational Site Number 8400012
state: Utah
city: Salt Lake City
country: United States
facility: Investigational Site Number 8400005
state: Utah
city: West Jordan
country: United States
facility: Investigational Site Number 8400014
state: Utah
city: Montreal
country: Canada
facility: Investigational Site Number 1241003
city: Pierrefonds
country: Canada
facility: Investigational Site Number 1241002
city: Quebec
country: Canada
facility: Investigational Site Number 1241001
Study officials:
affiliation: Sanofi Pasteur, a Sanofi Company
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: Chang LJ, Anderson EJ, Jeanfreau R, He Y, Hicks B, Shrestha A, Pandey A, Landolfi V, DeBruijn I; QHD04 Study Group. Safety and immunogenicity of high doses of quadrivalent influenza vaccine in children 6 months through <18 years of age: A randomized controlled phase II dose-finding trial. Vaccine. 2021 Mar 12;39(11):1572-1582. doi: 10.1016/j.vaccine.2021.02.014. Epub 2021 Feb 18.