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

Phase 3
Suspended
Conditions
Influenza
Interventions
Biological: Quadrivalent influenza vaccine, high-dose
Biological: Quadrivalent influenza vaccine, standard dose
Registration Number
NCT04544267
Lead Sponsor
Sanofi Pasteur, a Sanofi Company
Brief Summary

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

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.

Recruitment & Eligibility

Status
SUSPENDED
Sex
All
Target Recruitment
13320
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
QIV-HDQuadrivalent influenza vaccine, high-doseOne 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.
QIV-SDQuadrivalent influenza vaccine, standard doseOne 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.
Primary Outcome Measures
NameTimeMethod
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)From 14 days after the first injection to 6 months after the last injection

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.

Secondary Outcome Measures
NameTimeMethod
Number of participants with ILI laboratory-confirmed as positive for viral strains similar to those contained in the vaccineFrom 14 days to maximum 6 months after the last injection

Laboratory-confirmed influenza is a positive influenza result on either PCR or viral culture.

Number of participants with ILI laboratory-confirmed as positive in participants aged 6 through 23 months for any influenza A or B typeFrom 14 days to maximum 6 months after the last injection

Laboratory-confirmed influenza is a positive influenza result on either PCR or viral culture.

Number of participants with ILI PCR-confirmed as positive for viral strains similar to those contained in the vaccineFrom 14 days to maximum 6 months after the last injection

PCR-confirmed influenza is a positive influenza result on PCR.

Geometric mean titer of influenza vaccine antibodiesDay 0 and 28 days after the last vaccination

Antibody titers are measured by HAI assay.

Number of participants with seroconversion or significant increase of titersDay 0 and 28 days after the last vaccination

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.

Number of participants with influenza vaccine antibody titer ≥ 10 (1/dilution [dil])Day 0 and 28 days after the last vaccination

Antibody titers are measured by HAI assay.

Number of participants with ILI laboratory-confirmed as positive for viral strains similar to those contained in the vaccine, according to previous vaccination statusFrom 14 days to maximum 6 months after the last injection

Laboratory-confirmed influenza is a positive influenza result on either PCR or viral culture.

Number of participants with ILI laboratory-confirmed as positive for viral strains similar to those contained in the vaccine, and associated with AOMFrom 14 days to maximum 6 months after the last injection

Laboratory-confirmed influenza is a positive influenza result on either PCR or viral culture. AOM is based on clinical diagnosis.

Number of participants with ILI laboratory-confirmed as positive for any influenza A or B type, and associated with acute lower respiratory infection (ALRI)From 14 days to maximum 6 months after the last injection

Laboratory-confirmed influenza is a positive influenza result on either PCR or viral culture.

Number of participants with ILI laboratory-confirmed as positive for any influenza A or B types and associated with hospitalizationFrom 14 days to maximum 6 months after the last injection

Laboratory-confirmed influenza is a positive influenza result on either PCR or viral culture.

Influenza SN antibody titerDay 0 and 28 days after the last vaccination

Antibody titers will be measured by the SN method

Number of participants with ILI laboratory-confirmed as positive for any influenza A or B type, according to previous vaccination statusFrom 14 days to maximum 6 months after the last injection

Laboratory-confirmed influenza is a positive influenza result on either PCR or viral culture.

Number of participants with ILI culture-confirmed as positive for viral strains similar to those contained in the vaccineFrom 14 days to maximum 6 months after the last injection

Culture-confirmed influenza is a positive influenza result on viral culture.

Participant with influenza vaccine antibody titer ≥ 40 (1/dil)Day 0 and 28 days after the last vaccination

Antibody titers are measured by HAI assay.

Detectable anti-NA antibody titerDay 0 and 28 days after the last vaccination

Detectable antibody titers are ≥ 10 (1/dil).

Number of participants with immediate adverse eventsWithin 30 minutes after vaccination

Immediate adverse events includes unsolicited systemic adverse events occuring within 30 minutes after vaccination.

Number of participants with solicited injection site and systemic reactionsWithin 7 days after vaccination

Injection site reactions: tenderness, erythema, swelling, induration, and bruising. Systemic reactions: fever, vomiting, crying abnormal, drowsiness, appetite lost, and irritability.

Number of participants with ILI laboratory-confirmed as positive for viral strains similar to those contained in the vaccine, and associated with ALRIFrom 14 days to maximum 6 months after the last injection

Laboratory-confirmed influenza is a positive influenza result on either PCR or viral culture.

Influenza SN antibody titer ratio28 days after the last vaccination

Ratio is calculated as fold increase in serum SN post-vaccination relative to Day 0. Antibody titers are measured by the SN method

Fold-increase in influenza SN antibody titer28 days after the last vaccination

Increase of titer \[post/pre\] ≥2 and ≥ 4. Antibody titers are measured by the SN method.

Anti-NA antibody titer ratio28 days after the last vaccination

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.

Number of participants with ILI laboratory-confirmed as positive for any influenza A or B type, and associated with acute otitis media (AOM)From 14 days to maximum 6 months after the last injection

Laboratory-confirmed influenza is a positive influenza result on either PCR or viral culture. AOM is based on clinical diagnosis.

Number of participants with ILI PCR-confirmed as positive for any influenza A or B typesFrom 14 days to maximum 6 months after the last injection

PCR-confirmed influenza is a positive influenza result on PCR.

Number of participants with ILI culture-confirmed as positive for any influenza A or B typesFrom 14 days to maximum 6 months after the last injection

Culture-confirmed influenza is a positive influenza result on viral culture.

Number of participants with ILI laboratory-confirmed as positive for viral strains similar to those contained in the vaccine and associated with hospitalizationFrom 14 days to maximum 6 months after the last injection

Laboratory-confirmed influenza is a positive influenza result on either PCR or viral culture.

Influenza vaccine antibody titer ratioDay 0 and 28 days after the last vaccination

Individual antibody titer ratio 28 days after the last vaccination /Day 0. Antibody titers are measured by HAI assay.

Detectable influenza SN antibody titerDay 0 and 28 days after the last vaccination

Detectable antibody titers are ≥ 10 \[1/dil\]

Fold-increase in anti-NA antibody titer28 days after the last vaccination

Increase of titer \[post/pre\] ≥2 and ≥ 4. Antibody titers are measured by enzyme-linked lectin assay.

Number of participants with serious adverse eventsFrom Day 0 to Day 180

Serious adverse events are collected throughout the study.

Number of participants with influenza SN antibody titer above predefined thresholds28 days after the last vaccination

Antibody titers are measured by the SN method. Titers levels assessed are ≥ 20 (1/dil), ≥ 40 (1/dil), and ≥ 80 (1/dil).

Anti-NA antibody titerDay 0 and 28 days after the last vaccination

Antibody titers are measured by enzyme-linked lectin assay

Number of participants with unsolicited adverse eventsWithin 28 days after vaccination

Unsolicited adverse events are events other than solicited reactions.

Number of participants with anti-NA antibody titer above predefined thresholds28 days after the last vaccination

Antibody titers are measured by enzyme-linked lectin assay. Titers levels assessed are ≥ 20 (1/dil), ≥ 40 (1/dil), and ≥ 80 (1/dil).

Number of participants with adverse events of special interestFrom Day 0 to Day 180

Adverse events of special interest are collected throughout the study.

Trial Locations

Locations (10)

Investigational Site Number :8400033

🇺🇸

Barnwell, South Carolina, United States

Investigational Site Number :8400001

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Atlanta, Georgia, United States

Investigational Site Number :8400006

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Salt Lake City, Utah, United States

Investigational Site Number :8400045

🇺🇸

Salt Lake City, Utah, United States

Investigational Site Number :8400027

🇺🇸

Dayton, Ohio, United States

Investigational Site Number :8400008

🇺🇸

San Diego, California, United States

Investigational Site Number :8400007

🇺🇸

Miami, Florida, United States

Investigational Site Number :8400009

🇺🇸

Metairie, Louisiana, United States

Investigational Site Number :8400032

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El Dorado, Kansas, United States

Investigational Site Number :8400005

🇺🇸

Bardstown, Kentucky, United States

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