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
Seqirus QIVc	QIVc	Cell-derived Quadrivalent Influenza Vaccine
Comparator	Comparator	Non-influenza Comparator (NesiVac-C)
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
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
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).
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): 60817-Health Index Multispecialty Clinic
🇵🇭
Bacoor, Philippines
60801-Chong Hua Hospital
🇵🇭
Cebu City, Philippines
71009-Perinatal HIV Research Unit, Tshepong Hospital
🇿🇦
Klerksdorp, South Africa
60810-UERM Memorial Medical Center
🇵🇭
Quezon City, Quezon, Philippines
58601-Al Shifa Research Centre
🇵🇰
Rawalpindi, Pakistan
60816-De La Salle Medical and Health Sciences Institute
🇵🇭
Dasmariñas, Philippines
60806-Mary Chiles General Hospital
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Manila, Philippines
71007-Allergy & Immunology Unit
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Cape Town, South Africa
76405-Phramongkutklao Hospital
🇹🇭
Ratchathewi, Bangkok, Thailand
71001-Be Part Yoluntu Centre
🇿🇦
Paarl, South Africa
71003-Soweto Clinical Trials Centre
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Soweto, South Africa
71005-Limpopo Clinical Research Initiative
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Thabazimbi, South Africa
60812-De La Salle Medical and Health Sciences Institute
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Dasmariñas, Philippines
71006-Madibeng Centre for Research
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Brits, South Africa
71004-Tread Research
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Cape Town, South Africa
71008-Clinical Trial Systems
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Pretoria, South Africa
61604-Hanna Czajka, Indywidualna Specjalistyczna Praktyka Lekarska
🇵🇱
Kraków, Poland
61608-Gabinet Lekarski Bartosz Korczowski
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Rzeszów, Poland
64206-S.C Centrul Clinic Mediquest S.R.L
🇷🇴
Sângeorgiu De Mureş, Romania
71002-Synergy Biomed Research Institute
🇿🇦
East London, South Africa
76404-Department of Tropical Pediatrics, Faculty of Tropical Medicine, Mahidol University
🇹🇭
Bangkok, Thailand
International Centre for Diarrhoeal Disease Research, Bangladesh
🇧🇩
Dhaka, Bangladesh
10007-MHAT Dr. Stamen Iliev AD
🇧🇬
Montana, Bulgaria
10006-UMHAT-Plovdiv AD
🇧🇬
Plovdiv, Bulgaria
20303-MUDr. Stefan Hrunka, Prakticky lekar pro deti a dorost
🇨🇿
Chlumec Nad Cidlinou, Czechia
20301-MUDr. Daniel Drazan, Prakticky lekar pro deti a dorost
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Jindřichův Hradec, Czechia
20304-MUDr. David Zeman s.r.o.
🇨🇿
Ostrava-poruba, Czechia
20302-MUDr. Daniela Pniakova s.r.o.
🇨🇿
Ostrava, Czechia
20305-MUDr. Iva Madejova, Prakticky lekar pro deti a dorost
🇨🇿
Pardubice, Czechia
34003-Clínica Médica y Dental CLIMEDENTY
🇭🇳
Tegucigalpa, Honduras
55401-Wellington Hospital
🇳🇿
Wellington, New Zealand
55403-Christchurch Clinical Studies Trust
🇳🇿
Christchurch, New Zealand
58604-The Aga Khan
🇵🇰
Karachi, Pakistan
45802-Hospital Sibu
🇲🇾
Sibu, Sarawak, Malaysia
58605-Avicenna Hospital
🇵🇰
Lahore, Pakistan
58607-Central Park Teaching Hospital
🇵🇰
Lahore, Pakistan
60808-University of the Philippines Manila Development Foundation Inc
🇵🇭
Ermita, Manila, Philippines
60814-Philippine General Hospital
🇵🇭
Manila, Philippines
60815-Philippine General Hospital
🇵🇭
Manila, Philippines
60811-UERM Memorial Medical Center
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Quezon City, Philippines
61605-Osrodek Badan Klinicznych IN-VIVO sp. z o.o.
🇵🇱
Bydgoszcz, Poland
61607-Gdanskie Centrum Zdrowia Sp. z o.o.
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Gdańsk, Poland
10003-UMHAT Dr. Georgi Stranski EAD
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Pleven, Bulgaria
10002-UMHAT Sveti Georgi EAD
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Plovdiv, Bulgaria
10009-Medical Center Unimed Eood
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Sevlievo, Bulgaria
61602-Niepubliczny Zaklad Lecznictwa Ambulatoryjnego Michalkowice
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Siemianowice Śląskie, Poland
61601-ETG Network- Skierniewice,Clinmed Research
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Skierniewice, Poland
61609-Szpital im. Swietej Jadwigi Slaskiej w Trzebnicy
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Trzebnica, Poland
64201-SC Sana Monitoring SRL.
🇷🇴
Bucuresti, Romania
64205-Sc Med Fam Apolo srl
🇷🇴
Călăraşi, Romania
76401-Vaccine Trial Centre, Faculty of Tropical Medicine, Mahidol University
🇹🇭
Bangkok, Thailand
80405-CI Dnipro Children's City CH #5 of Dnipro City Council
🇺🇦
Dnipro, Ukraine
23305-Vee Family Doctor's Centre
🇪🇪
Paide, Estonia
23301-Innomedica OÜ
🇪🇪
Tallinn, Estonia
23304-Merelahe Family Doctors Center
🇪🇪
Tallinn, Estonia
23307-Tallinn Children's Hospital
🇪🇪
Tallinn, Estonia
23303-Al Mare Perearstikeskus OU
🇪🇪
Tallin, Estonia
23302-Clinical Research Centre
🇪🇪
Tartu, Estonia
34001-Demedica
🇭🇳
San Pedro Sula, Honduras
34002-Inversiones en Investigación Médica (INVERIME)
🇭🇳
Tegucigalpa, Honduras
45804-Clinical Research Centre (CRC), Hospital Tuanku Fauziah
🇲🇾
Kangar, Perlis, Malaysia
45803-Sarawak General Hospital
🇲🇾
Kuching, Sarawak, Malaysia
10008-Medical Center Viva Feniks
🇧🇬
Dobrich, Bulgaria
10004-SHATPPD Dr Dimitar Gramatikov Ruse EOOD
🇧🇬
Ruse, Bulgaria
42802-OLVI Medical Centre
🇱🇻
Daugavpils, Latvia
45805-Klinik Kesihatan Putrajaya Presint 9
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Putrajaya, Wilyah Persekutuan Putrajaya, Malaysia
58602-Shifa International Hospital
🇵🇰
Islamabad, Pakistan
45801-University Malaya Medical Centre
🇲🇾
Kuala Lumpur, Malaysia
61603-Jerzy Brzostek Prywatny Gabinet Lekarski
🇵🇱
Dębica, Poland
60818-Philippine General Hospital
🇵🇭
Manila, Philippines
60813-Philippine Children's Medical Center
🇵🇭
Quezon City, Philippines
64202-Spitalul Municipal Caracal
🇷🇴
Caracal, Romania
80404-Reg Mun NPE Chernivtsi RCCH Infectious Dept for Infants SHEI of UBSMU
🇺🇦
Chernivtsi, Ukraine
80401-Vinnytsia RCCH Policlinic Dept Vinnytsia M.I.Pyrogov NMU
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Vinnytsia, Ukraine