Study on a High-Dose Quadrivalent Influenza Vaccine Compared With Standard-Dose Quadrivalent Influenza Vaccine in Children 6 Months Through 35 Months of Age (QHD00014)

Efficacy, Immunogenicity, and Safety of High-Dose Quadrivalent Influenza Vaccine Compared With Standard-Dose Quadrivalent Influenza Vaccine in Children 6 Months Through 35 Months of Age

The primary objective of the study is to compare the clinical efficacy of high-dose quadrivalent influenza vaccine (QIV-HD) to standard-dose quadrivalent influenza vaccine (QIV-SD) in participants 6 months through 35 months of age for the prevention of laboratory-confirmed influenza illness caused by any influenza A or B type.

The secondary objectives of the study are:

• To compare QIV-HD to QIV-SD:
• in participants 6 months through 35 months of age for the prevention of laboratory-confirmed influenza illness caused by any influenza A or B type using a more stringent threshold
• in participants 6 months through 35 months of age for the prevention of laboratory-confirmed protocol-defined influenza-like illness caused by viral strains similar to those contained in the vaccine.
• in participants 6 months through 23 months of age for the prevention of laboratory-confirmed influenza illness caused by any influenza A or B types.
• To compare hemagglutination inhibition (HAI) immune response of QIV-HD to QIV-SD in participants 6 months through 35 months of age
• To describe the HAI, seroneutralization (SN), and anti-neuraminidase (NA) immune response
• To describe the immune response to revaccination in Season 3 (Northern Hemisphere)
• To describe the safety profile of each vaccine

Study Overview

• Status: Suspended
• Conditions: Influenza
• Intervention / Treatment: Biological: Quadrivalent influenza vaccine, high-dose; Biological: Quadrivalent influenza vaccine, standard dose

Detailed Description

The study is planned to start in the second half of 2020 with the Sentinel Safety Cohort. Following the Sentinel Safety Cohort, the main efficacy cohort will be conducted during the 2021-2022 Northern Hemisphere influenza season (Season 1), the 2021-2022 Southern Hemisphere influenza season (Season 2), and the 2021-2022-2023 Northern Hemisphere influenza season (Season 3).

Participants will receive either 1 or 2 doses of the study vaccine depending on whether they were previously influenza vaccinated or previously influenza unvaccinated, respectively.

Study duration per participant is approximately 6 to 7 months.

• Study Type: Interventional
• Enrollment (Anticipated): 13320
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123-1881
      • Investigational Site Number :8400008
  • Florida
    • Miami, Florida, United States, 33186
      • Investigational Site Number :8400007
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Investigational Site Number :8400001
  • Kansas
    • El Dorado, Kansas, United States, 67042
      • Investigational Site Number :8400032
  • Kentucky
    • Bardstown, Kentucky, United States, 40004
      • Investigational Site Number :8400005
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Investigational Site Number :8400009
  • Ohio
    • Dayton, Ohio, United States, 45414
      • Investigational Site Number :8400027
  • South Carolina
    • Barnwell, South Carolina, United States, 29812
      • Investigational Site Number :8400033
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Investigational Site Number :8400006
    • Salt Lake City, Utah, United States, 84121
      • Investigational Site Number :8400045

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 2 years (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion criteria :

• Aged 6 to 35 months on the day of the first study visit
• Informed consent form has been signed and dated by the parent(s) or guardian(s) and by an independent witness, if required by local regulations.
• Participant and parent / guardian are able to attend all scheduled visits and to comply with all study procedures.
• Covered by health insurance if required by local regulations
• For Season 3 Re-vaccination Cohort: eligible participants must have been enrolled in the Season 1 (2021-2022 Northern Hemisphere season) immunogenicity subset and must have completed all study procedures (ie, blood draws and vaccinations) in Season 1.

Exclusion criteria:

• 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.
• For all participants: Receipt of any vaccine in the 30 days preceding the first study vaccination. For participants in immunogenicity subset: 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 preceding 6 months with either the study vaccine or another influenza vaccine
• Receipt of immune globulins, blood or blood-derived products in the past 3 months.
• Known or suspected congenital or acquired immunodeficiency (eg, HIV); 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. Exception: participants with an egg allergy are allowed to enroll in the study.
• Thrombocytopenia, bleeding disorder, or receipt of anticoagulants that based on Investigator's judgment contraindicate intramuscular vaccination
• Chronic illness that, in the opinion of the investigator, is 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 C [≥ 100.4 F]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided.
• Identified as natural or adopted child of the Investigator or employee with direct involvement in the proposed study.
• Personal or family history of Guillain-Barre 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.
• For Season 3 (2022-2023 Northern Hemisphere) main cohort: participants who were enrolled in a previous study season are excluded from Season 3, with the exception of the Re-vaccination Cohort.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: QIV-HD; One injection of QIV-HD on Day 0. For participants for whom 2 doses of influenza vaccine are recommended, a second dose is administered on Day 28.	Biological: Quadrivalent influenza vaccine, high-dose; Pharmaceutical form: suspension for injection in a pre-filled syringe; route of administration: intramuscular
ACTIVE_COMPARATOR: QIV-SD; One injection of QIV-SD on Day 0. For participants for whom 2 doses of influenza vaccine are recommended, a second dose is administered on Day 28.	Biological: Quadrivalent influenza vaccine, standard dose; Pharmaceutical form: suspension for injection in a pre-filled syringe; route of administration: intramuscular

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with laboratory-confirmed influenza illness caused by any influenza viral types/subtypes, in association with a protocol-defined influenza-like illness (ILI)	Laboratory-confirmed influenza is a positive influenza result on either polymerase chain reaction (PCR) or viral culture. A protocol-defined ILI is occurrence of fever concurrently with protocol pre-defined clinical symptoms.	From 14 days after the first injection to 6 months after the last injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with ILI laboratory-confirmed as positive for viral strains similar to those contained in the vaccine	Laboratory-confirmed influenza is a positive influenza result on either PCR or viral culture.	From 14 days to maximum 6 months after the last injection
Number of participants with ILI laboratory-confirmed as positive in participants aged 6 through 23 months for any influenza A or B type	Laboratory-confirmed influenza is a positive influenza result on either PCR or viral culture.	From 14 days to maximum 6 months after the last injection
Number of participants with ILI laboratory-confirmed as positive for any influenza A or B type, according to previous vaccination status	Laboratory-confirmed influenza is a positive influenza result on either PCR or viral culture.	From 14 days to maximum 6 months after the last injection
Number of participants with ILI laboratory-confirmed as positive for viral strains similar to those contained in the vaccine, according to previous vaccination status	Laboratory-confirmed influenza is a positive influenza result on either PCR or viral culture.	From 14 days to maximum 6 months after the last injection
Number of participants with ILI laboratory-confirmed as positive for any influenza A or B type, and associated with acute otitis media (AOM)	Laboratory-confirmed influenza is a positive influenza result on either PCR or viral culture. AOM is based on clinical diagnosis.	From 14 days to maximum 6 months after the last injection
Number of participants with ILI laboratory-confirmed as positive for viral strains similar to those contained in the vaccine, and associated with AOM	Laboratory-confirmed influenza is a positive influenza result on either PCR or viral culture. AOM is based on clinical diagnosis.	From 14 days to maximum 6 months after the last injection
Number of participants with ILI laboratory-confirmed as positive for any influenza A or B type, and associated with acute lower respiratory infection (ALRI)	Laboratory-confirmed influenza is a positive influenza result on either PCR or viral culture.	From 14 days to maximum 6 months after the last injection
Number of participants with ILI laboratory-confirmed as positive for viral strains similar to those contained in the vaccine, and associated with ALRI	Laboratory-confirmed influenza is a positive influenza result on either PCR or viral culture.	From 14 days to maximum 6 months after the last injection
Number of participants with ILI PCR-confirmed as positive for viral strains similar to those contained in the vaccine	PCR-confirmed influenza is a positive influenza result on PCR.	From 14 days to maximum 6 months after the last injection
Number of participants with ILI culture-confirmed as positive for viral strains similar to those contained in the vaccine	Culture-confirmed influenza is a positive influenza result on viral culture.	From 14 days to maximum 6 months after the last injection
Number of participants with ILI PCR-confirmed as positive for any influenza A or B types	PCR-confirmed influenza is a positive influenza result on PCR.	From 14 days to maximum 6 months after the last injection
Number of participants with ILI culture-confirmed as positive for any influenza A or B types	Culture-confirmed influenza is a positive influenza result on viral culture.	From 14 days to maximum 6 months after the last injection
Number of participants with ILI laboratory-confirmed as positive for any influenza A or B types and associated with hospitalization	Laboratory-confirmed influenza is a positive influenza result on either PCR or viral culture.	From 14 days to maximum 6 months after the last injection
Number of participants with ILI laboratory-confirmed as positive for viral strains similar to those contained in the vaccine and associated with hospitalization	Laboratory-confirmed influenza is a positive influenza result on either PCR or viral culture.	From 14 days to maximum 6 months after the last injection
Geometric mean titer of influenza vaccine antibodies	Antibody titers are measured by HAI assay.	Day 0 and 28 days after the last vaccination
Number of participants with seroconversion or significant increase of titers	Seroconversion for participants with a pre-vaccination titer < 10 (1/dil): post-injection titer ≥ 40 (1/dil) on 28 days after the last vaccination or significant increase for participants with a pre-vaccination titer ≥ 10 (1/dil): ≥ 4-fold increase from pre- to post-injection titer on 28 days after the last vaccination. Antibody titers are measured by HAI assay.	Day 0 and 28 days after the last vaccination
Number of participants with influenza vaccine antibody titer ≥ 10 (1/dilution [dil])	Antibody titers are measured by HAI assay.	Day 0 and 28 days after the last vaccination
Influenza vaccine antibody titer ratio	Individual antibody titer ratio 28 days after the last vaccination /Day 0. Antibody titers are measured by HAI assay.	Day 0 and 28 days after the last vaccination
Participant with influenza vaccine antibody titer ≥ 40 (1/dil)	Antibody titers are measured by HAI assay.	Day 0 and 28 days after the last vaccination
Influenza SN antibody titer	Antibody titers will be measured by the SN method	Day 0 and 28 days after the last vaccination
Influenza SN antibody titer ratio	Ratio is calculated as fold increase in serum SN post-vaccination relative to Day 0. Antibody titers are measured by the SN method	28 days after the last vaccination
Number of participants with influenza SN antibody titer above predefined thresholds	Antibody titers are measured by the SN method. Titers levels assessed are ≥ 20 (1/dil), ≥ 40 (1/dil), and ≥ 80 (1/dil).	28 days after the last vaccination
Fold-increase in influenza SN antibody titer	Increase of titer [post/pre] ≥2 and ≥ 4. Antibody titers are measured by the SN method.	28 days after the last vaccination
Detectable influenza SN antibody titer	Detectable antibody titers are ≥ 10 [1/dil]	Day 0 and 28 days after the last vaccination
Anti-NA antibody titer	Antibody titers are measured by enzyme-linked lectin assay	Day 0 and 28 days after the last vaccination
Anti-NA antibody titer ratio	Ratio is calculated as fold increase in anti-NA antibodies post-vaccination relative to Day 0. Antibody titers are measured by enzyme-linked lectin assay.	28 days after the last vaccination
Number of participants with anti-NA antibody titer above predefined thresholds	Antibody titers are measured by enzyme-linked lectin assay. Titers levels assessed are ≥ 20 (1/dil), ≥ 40 (1/dil), and ≥ 80 (1/dil).	28 days after the last vaccination
Fold-increase in anti-NA antibody titer	Increase of titer [post/pre] ≥2 and ≥ 4. Antibody titers are measured by enzyme-linked lectin assay.	28 days after the last vaccination
Detectable anti-NA antibody titer	Detectable antibody titers are ≥ 10 (1/dil).	Day 0 and 28 days after the last vaccination
Number of participants with immediate adverse events	Immediate adverse events includes unsolicited systemic adverse events occuring within 30 minutes after vaccination.	Within 30 minutes after vaccination
Number of participants with solicited injection site and systemic reactions	Injection site reactions: tenderness, erythema, swelling, induration, and bruising. Systemic reactions: fever, vomiting, crying abnormal, drowsiness, appetite lost, and irritability.	Within 7 days after vaccination
Number of participants with unsolicited adverse events	Unsolicited adverse events are events other than solicited reactions.	Within 28 days after vaccination
Number of participants with serious adverse events	Serious adverse events are collected throughout the study.	From Day 0 to Day 180
Number of participants with adverse events of special interest	Adverse events of special interest are collected throughout the study.	From Day 0 to Day 180

Collaborators and Investigators

• Sponsor: Sanofi Pasteur, a Sanofi Company

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 15, 2020
• Primary Completion (ANTICIPATED): July 1, 2026
• Study Completion (ANTICIPATED): July 1, 2026

Study Registration Dates

• First Submitted: September 3, 2020
• First Submitted That Met QC Criteria: September 3, 2020
• First Posted (ACTUAL): September 10, 2020

Study Record Updates

• Last Update Posted (ACTUAL): May 9, 2022
• Last Update Submitted That Met QC Criteria: May 3, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: QHD00014; U1111-1243-5993 (OTHER: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No