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

NCT ID: NCT03698279

Last Updated: 2022-04-04

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

665 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-10-09

Study Completion Date

2019-10-16

Brief Summary

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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

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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.

Conditions

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Influenza

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

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 Study Purpose

PREVENTION

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
Modified double-blind: the participant's parent / legally acceptable representative, the Investigator, and other study personnel remained unaware of the treatment assignments throughout the trial. An unblinded vaccine administrator administered the appropriate vaccine but was not involved in safety data collection.

Study Groups

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Group 1: QIV-HD 30 μg (US: 6 months to 17 years)

Participants from United States (US) (aged 6 months to 17 years) received single injection of 30 microgram (μg) QIV-HD, intramuscularly (IM) at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.

Group Type EXPERIMENTAL

High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 30 μg (split-virion, inactivated)

Intervention Type BIOLOGICAL

Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: IM

Group 2: QIV-HD 45 μg (US: 6 months to 17 years)

Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.

Group Type EXPERIMENTAL

High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 45 μg, (split-virion, inactivated)

Intervention Type BIOLOGICAL

Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: IM

Group 3: QIV-HD, 60 μg (US: 6 months to 17 years)

Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.

Group Type EXPERIMENTAL

High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 60 µg (split-virion, inactivated)

Intervention Type BIOLOGICAL

Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: IM

Group 4: Pooled QIV-SD, 15 μg (US: 6 months to 17 years)

Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.

Group Type ACTIVE_COMPARATOR

Fluarix Quadrivalent Influenza vaccine (Unadjuvanted QIV-SD) (Inactivated)

Intervention Type BIOLOGICAL

Pharmaceutical form: Solution for injection Route of administration: IM

Group 5: QIV-HD, 60 μg (Canada: 6 to <24 months)

Participants from Canada (aged 6 to less than \[\<\] 24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.

Group Type EXPERIMENTAL

High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 60 µg (split-virion, inactivated)

Intervention Type BIOLOGICAL

Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: IM

Group 6: Adjuvanted TIV (Canada: 6 to <24 months)

Participants from Canada (aged 6 to \<24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.

Group Type ACTIVE_COMPARATOR

FLUAD Pediatric (adjuvanted TIV) (Surface Antigen, Inactivated)

Intervention Type BIOLOGICAL

Pharmaceutical form: Solution for injection Route of administration: IM

Interventions

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High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 30 μg (split-virion, inactivated)

Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: IM

Intervention Type BIOLOGICAL

High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 45 μg, (split-virion, inactivated)

Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: IM

Intervention Type BIOLOGICAL

High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 60 µg (split-virion, inactivated)

Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: IM

Intervention Type BIOLOGICAL

Fluarix Quadrivalent Influenza vaccine (Unadjuvanted QIV-SD) (Inactivated)

Pharmaceutical form: Solution for injection Route of administration: IM

Intervention Type BIOLOGICAL

FLUAD Pediatric (adjuvanted TIV) (Surface Antigen, Inactivated)

Pharmaceutical form: Solution for injection Route of administration: IM

Intervention Type BIOLOGICAL

Eligibility Criteria

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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.
Minimum Eligible Age

6 Months

Maximum Eligible Age

17 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Sanofi Pasteur, a Sanofi Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi Pasteur, a Sanofi Company

Locations

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Investigational Site Number 8400004

San Diego, California, United States

Site Status

Investigational Site Number 8400001

Miami, Florida, United States

Site Status

Investigational Site Number 8400002

Atlanta, Georgia, United States

Site Status

Investigational Site Number 8400013

El Dorado, Kansas, United States

Site Status

Investigational Site Number 8400015

Newton, Kansas, United States

Site Status

Investigational Site Number 8400009

Wichita, Kansas, United States

Site Status

Investigational Site Number 8400007

Metairie, Louisiana, United States

Site Status

Investigational Site Number 8400010

Las Vegas, Nevada, United States

Site Status

Investigational Site Number 8400011

Warwick, Rhode Island, United States

Site Status

Investigational Site Number 8400003

Salt Lake City, Utah, United States

Site Status

Investigational Site Number 8400012

Salt Lake City, Utah, United States

Site Status

Investigational Site Number 8400005

Salt Lake City, Utah, United States

Site Status

Investigational Site Number 8400014

West Jordan, Utah, United States

Site Status

Investigational Site Number 1241003

Montreal, , Canada

Site Status

Investigational Site Number 1241002

Pierrefonds, , Canada

Site Status

Investigational Site Number 1241001

Québec, , Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type RESULT
PMID: 33610374 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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U1111-1189-3713

Identifier Type: OTHER

Identifier Source: secondary_id

2018-005026-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

QHD04

Identifier Type: -

Identifier Source: org_study_id

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