Efficacy Study With QIVc in Pediatric Subjects

Phase 3

Completed

Conditions: Influenza, Human

Interventions: Biological: QIVc
Biological: Comparator

Registration Number: NCT03932682

Lead Sponsor: Seqirus

Brief Summary: This phase 3 clinical study is a randomized, observer-blind, multicenter study of QIVc versus a non-influenza vaccine in subjects 6 months though 47 months of age. The purpose of this study is to evaluate efficacy of QIVc in the prevention of laboratory confirmed influenza A or B disease in children 6 through 47 months of age, compared to a non-influenza vaccine.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 5723

Inclusion Criteria

In order to participate in this study, all subjects must meet all of the inclusion criteria described.

Individuals of 6 through 47 months of age on the day of informed consent.
Individuals whose parent(s)/Legally Acceptable Representative (LAR) have voluntarily given written informed consent after the nature of the study has been explained according to local regulatory requirements, prior to study entry.
Individuals who can comply with study procedures including follow-up.
Individuals in generally good health as per the Investigator's medical judgement.

If applicable, prior to receipt of second study vaccination, subjects must be evaluated to confirm that they are eligible for subsequent vaccination. If subjects do not meet the criteria of the original inclusion criteria listed above, they should not receive additional vaccinations.

Exclusion Criteria

Acute (severe) febrile illness. Enrollment could be considered if the fever is absent for 72 hours.
History of any anaphylaxis, serious vaccine reactions or hypersensitivity, including allergic reactions, to any component of vaccine or medical equipment whose use is foreseen in this study.
Clinical conditions representing a contraindication to intramuscular vaccination and blood draws. These may include known bleeding disorders, or treatment with anticoagulants in the 3 weeks preceding vaccination.
A known history of Guillain-Barré Syndrome or other demyelinating diseases such as encephalomyelitis and transverse myelitis.
Abnormal function of the immune system resulting from a clinical condition
Received influenza vaccination or has had documented influenza disease in the last 6 months prior to informed consent.
Prior vaccination to prevent Neisseria meningitides serogroup C disease or prior infection caused by this organism.

Additional eligibility criteria are provided in the study protocol.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
QIVc	QIVc	Cell-derived Quadrivalent Influenza Vaccine
Comparator	Comparator	Non-influenza Comparator

Primary Outcome Measures

Name	Time	Method
Efficacy Endpoint: First Occurrence of Reverse Transcription-polymerase Chain Reaction (RT-PCR) Confirmed Influenza, Due to Any Influenza Type A and/or B Virus Regardless of Antigenic Match	>14 days after last vaccination in the treatment period up to Day 181 or end of influenza season, whichever was longer (previously vaccinated subjects), or up to Day 209 or end of influenza season, whichever was longer (not previously vaccinated subjects)	First occurrence of RT-PCR confirmed influenza, due to any influenza Type A and/or B virus regardless of antigenic match to the influenza strains selected for the seasonal influenza vaccine, occurring at \>14 days after the last vaccination and until the end of the influenza season, in association with protocol-defined influenza-like illness (ILI) symptoms
Efficacy Endpoint: First Occurrence of Culture Confirmed Influenza, Due to Influenza Type A and/or B Virus Antigenically Matched by Ferret Antigenicity Testing to the Strains Selected for the Seasonal Influenza Vaccine	>14 days after last vaccination in the treatment period up to Day 181 or end of influenza season, whichever was longer (previously vaccinated subjects), or up to Day 209 or end of influenza season, whichever was longer (not previously vaccinated subjects)	First occurrence of culture confirmed influenza, due to influenza Type A and/or B virus antigenically matched by ferret antigenicity testing to the strains selected for the seasonal influenza vaccine, occurring at \>14 days after the last vaccination and until the end of the influenza season, in association with protocol-defined ILI symptoms

Secondary Outcome Measures

Name	Time	Method
Efficacy Endpoint: First Occurrence of Culture Confirmed Influenza Caused by Influenza Virus Strains Antigenically Dissimilar to the Influenza Strains Selected for the Seasonal Influenza Vaccine	>14 days after last vaccination in the treatment period up to Day 181 or end of influenza season, whichever was longer (previously vaccinated subjects), or up to Day 209 or end of influenza season, whichever was longer (not previously vaccinated subjects)	First occurrence of culture confirmed influenza caused by influenza virus strains antigenically dissimilar to the influenza strains selected for the seasonal vaccine occurring at \>14 days after the last vaccination and until the end of the influenza season, in association with protocol-defined ILI symptoms
Immunogenicity Endpoint: Geometric Mean Ratio (GMR) (HI Assay)	Day 1 through Day 29 for previously vaccinated subjects; Day 1 through Day 57 for not previously vaccinated subjects	The measures for immunogenicity are determined by a hemagglutination inhibition (HI) assay prior to first vaccination and 28 days after last vaccination for all four influenza strains GMR is the geometric mean of the fold increase of postvaccination HI titer over the prevaccination HI titer Adjusted GMRs are presented
Immunogenicity Endpoint: Prevaccination and Postvaccination Geometric Mean Titer (GMT) (MN Assay)	Day 1 and Day 29 for previously vaccinated subjects; Day 1 and Day 57 for not previously vaccinated subjects	The measures for immunogenicity are determined by a microneutralization (MN) assay prior to first vaccination and 28 days after last vaccination for all four influenza strains
Immunogenicity Endpoint: Seroconversion Rates (SCR) (MN Assay)	Day 1 through Day 29 for previously vaccinated subjects; Day 1 through Day 57 for not previously vaccinated subjects	The measures for immunogenicity are determined by a MN assay prior to first vaccination and 28 days after last vaccination for all four influenza strains SCR is defined as the percentage of subjects with either a prevaccination MN titer \<1:10 and a postvaccination MN titer ≥1:40, or a prevaccination MN titer ≥1:10 and a ≥4-fold increase in postvaccination MN titer
Immunogenicity Endpoint: Geometric Mean Ratio (GMR) (MN Assay)	Day 1 through Day 29 for previously vaccinated subjects; Day 1 through Day 57 for not previously vaccinated subjects	The measures for immunogenicity are determined by a MN assay prior to first vaccination and 28 days after last vaccination for all four influenza strains GMR is the geometric mean of the fold increase of post-vaccination MN titer over the pre-vaccination MN titer
Safety Endpoint: Percentage of Subjects With Solicited Local and Systemic Adverse Events (AEs)	7 days following each vaccination in the treatment period, ie, Day 1 to Day 7 for previously vaccinated subjects and Day 1 to Day 7 and Day 29 to Day 35 for not previously vaccinated subjects	Percentage of subjects with solicited local and systemic AEs assessed for 7 days following each vaccination in the QIVc group and in the comparator group
Safety Endpoint: Percentage of Subjects With Unsolicited AEs	28 days after each vaccination in the treatment period, ie, Day 1 to Day 29 for previously vaccinated subjects and Day 1 to Day 57 for not previously vaccinated subjects	Percentage of subjects with any unsolicited AEs assessed in the QIVc group and in the comparator group until 28 days after each vaccination
Safety Endpoint: Percentage of Subjects With SAEs, NOCDs, AEs Leading to Withdrawal From the Study or Vaccination	Day 1 through Study Completion, ie, Day 1 to Day 181 or end of influenza season, whichever was longer, for previously vaccinated subjects and Day 1 to Day 209 or end of influenza season, whichever was longer, for not previously vaccinated subjects	Percentage of subjects with serious adverse events (SAEs), new onset of chronic disease (NOCD), AEs leading to withdrawal from the study or vaccination, and all medications associated with these events in the QIVc group and in the comparator group Note: The time frame for assessment of these AEs was Day 1 through Study Completion as indicated below. Subjects aged 6 months through 11 months at enrollment in countries without NeisVac-C vaccine marketing authorization had an additional study visit 28 days later (ie, Day 237).
Efficacy Endpoint: First Occurrence of Culture Confirmed Influenza Due to Any Influenza Type A and/or Type B Virus Regardless of Antigenic Match to the Influenza Strains Selected for the Seasonal Influenza Vaccine	>14 days after last vaccination in the treatment period up to Day 181 or end of influenza season, whichever was longer (previously vaccinated subjects), or up to Day 209 or end of influenza season, whichever was longer (not previously vaccinated subjects)	First occurrence of culture confirmed influenza due to any influenza Type A and/or Type B virus regardless of antigenic match to the influenza strains selected for the seasonal influenza vaccine, occurring at \>14 days after the last vaccination and until the end of the influenza season, in association with protocol-defined ILI symptoms
Efficacy Endpoint: First Occurrence of RT-PCR Confirmed Moderate-to-severe Influenza Due to Any Influenza Type A and/or Type B Virus Regardless of Antigenic Match to the Influenza Strains Selected for the Seasonal Influenza Vaccine	>14 days after last vaccination in the treatment period up to Day 181 or end of influenza season, whichever was longer (previously vaccinated subjects), or up to Day 209 or end of influenza season, whichever was longer (not previously vaccinated subjects)	First occurrence of RT-PCR confirmed moderate-to-severe influenza due to any influenza Type A and/or Type B virus regardless of antigenic match to the influenza strains selected for the seasonal influenza vaccine, occurring at \>14 days after the last vaccination and until the end of the influenza season
Immunogenicity Endpoint: Prevaccination and Postvaccination Geometric Mean Titer (GMT) (HI Assay)	Day 1 and Day 29 for previously vaccinated subjects; Day 1 and Day 57 for not previously vaccinated subjects	The measures for immunogenicity are determined by a hemagglutination inhibition (HI) assay prior to first vaccination and 28 days after last vaccination for all four influenza strains HI = hemagglutination inhibition Adjusted GMTs are presented
Immunogenicity Endpoint: Seroconversion Rates (SCR) (HI Assay)	Day 1 through Day 29 for previously vaccinated subjects; Day 1 through Day 57 for not previously vaccinated subjects	The measures for immunogenicity are determined by a HI assay prior to first vaccination and 28 days after last vaccination for all four influenza strains SCR is defined as the percentage of subjects with either a prevaccination HI titer \<1:10 and a postvaccination HI titer ≥1:40, or a prevaccination HI titer ≥1:10 and a ≥4-fold increase in postvaccination HI titer
Safety Endpoint: Percentage of Subjects With Medically-attended AEs	If a subject experienced an ILI during approximately 8 months of study participation, medically-attended AEs were collected for the 30-day period after onset of the ILI (defined as the first day that a subject meets the criteria for protocol-defined ILI)	Percentage of subjects with medically-attended AEs within 30 days after ILI onset in the QIVc group and in the comparator group

Trial Locations

Locations (74): International Centre for Diarrhoeal Disease Research, Bangladesh
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Dhaka, Bangladesh
10008-Medical Center Viva Feniks
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Dobrich, Bulgaria
10007-MHAT Dr. Stamen Iliev AD
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Montana, Bulgaria
10003-UMHAT Dr. Georgi Stranski EAD
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Pleven, Bulgaria
10002-UMHAT Sveti Georgi EAD
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Plovdiv, Bulgaria
10006-UMHAT-Plovdiv AD
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Plovdiv, Bulgaria
10004-SHATPPD Dr Dimitar Gramatikov Ruse EOOD
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Ruse, Bulgaria
10009-Medical Center Unimed Eood
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Sevlievo, Bulgaria
20303-MUDr. Stefan Hrunka, Prakticky lekar pro deti a dorost
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Chlumec Nad Cidlinou, Czechia
20301-MUDr. Daniel Drazan, Prakticky lekar pro deti a dorost
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Jindřichův Hradec, Czechia
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International Centre for Diarrhoeal Disease Research, Bangladesh
🇧🇩Dhaka, Bangladesh