Clinical trial NCT03165617: Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of QIVc in Subjects ≥2 to <18 Years of Age
Official title: A Phase III/IV, Stratified, Randomized, Observer Blind, Multicenter Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of a Cell-Based Quadrivalent Subunit Influenza Virus Vaccine Compared to Non-Influenza Comparator Vaccine in Subjects ≥2 to <18 Years of Age
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza, Human
Keywords: Influenza vaccine
Lead sponsor: Seqirus
Sponsor class: INDUSTRY
First posted: 2017-05-24
Enrollment: 4514
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Phase 3/4
Primary purpose: PREVENTION

Brief summary: This Phase 3/4, randomized, observer-blind, multi-center study, stratified study evaluated the immune (antibody) response, efficacy and safety of a cell-derived quadrivalent subunit influenza virus vaccine (Seqirus QIVc) in comparison with a non-influenza comparator, meningococcal serogroup A, C, W-135, and Y (Menveo®, GlaxoSmithKline Biologicals, S.A.) in healthy pediatric subjects ≥2 Years to \<18 Years of Age

Detailed description: This Phase 3/4, randomized, observer-blind, multi-center, stratified study evaluated the efficacy, safety, and immunogenicity of a cell-derived quadrivalent subunit influenza virus vaccine (Seqirus QIVc) compared to a non-influenza comparator vaccine in healthy male and female participants between 2 to \<18 years of age. A total of 4514 children/teens were randomized, receiving either QIVc or the non-influenza comparator vaccine. The comparator was (meningococcal \[Groups A, C, W-135, and Y\] oligosaccharide diphtheria CRM197 conjugate vaccine \[Men ACWY\]). Randomized enrollment was stratified in a 1:1 ratio via an Interactive Response Technology (IRT) system which assigned the participants into two age cohorts: 2 to \<9 years of age and 9 to \<18 years of age. Subjects between 2 to \<9 years of age were further stratified by previous influenza vaccine status ("previously vaccinated" or "not previously vaccinated").

Eligibility criteria: Inclusion Criteria:

* Male or female ≥2 to \<18 years of age on the day of the first study vaccination
* Subject's parent(s) or legal guardian(s) who was/were able to give informed consent/dissent after the nature of the study had been explained in accordance with the practices described in the study and according to local regulatory requirements
* If the subject was of an age where, according to local regulations, informed assent was required, he/she must have provided assent to participate in the study
* Subject/subject's parent(s) or legal guardian(s) was/were able to comply with study procedures and was/were available for follow-up; and
* Subject was in generally good health as per the investigator's medical judgment

Exclusion Criteria:

* Clinical signs of fever and/or an oral temperature of ≥100.4°F (38.0°C) within 3 days prior to vaccination;
* A known history of any anaphylaxis, serious vaccine reactions or hypersensitivity to any of the vaccine components described in the Investigator's Brochure, or had any of the contraindications listed in the package insert of the comparator vaccine;
* A history of Guillain-Barré syndrome or other de-myelinating diseases such as encephalomyelitis and transverse myelitis;
* Female subject of childbearing potential (ie, post onset of menarche and before natural or induced menopause), sexually active, and who did not use any acceptable contraceptive methods for at least 2 months prior to study entry and who did not intend to use any acceptable contraceptive methods throughout subject participation (acceptable contraceptive methods included: abstinence; hormonal contraceptive \[such as oral, injection, transdermal patch, implant\]; diaphragm with spermicide; tubal occlusion device; intrauterine device \[IUD\]; tubal ligation; male partner using condom; or male partner having been vasectomized);
* Pregnant or breast feeding female;
* Subject and/or subject's parent/guardians who were not able to comprehend or follow all required study procedures for the entire period of the study;
* Received prior Meningococcal ACWY vaccination that conflicted with national recommendations or local practices for the timing of the primary or the booster vaccination;
* Received influenza vaccination or had documented influenza disease in the last 6 months;
* Known or suspected congenital or acquired immunodeficiency; or received immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or systemic corticosteroid therapy (prednisone or equivalent) at any dose for more than 2 consecutive weeks (14 days) within the past 3 months. Topical, inhaled and intra-nasal corticosteroids were permitted. Intermittent use (1 dose in 30 days) of intra-articular corticosteroids was also permitted;
* Administration of immunoglobulin and/or any blood products within the 3 months preceding vaccination, or administration was planned during the study;
* Participated in any clinical study with another investigational product within 30 days prior to first study visit or intended to participate in another clinical study at any time during the conduct of this study. Concomitant participation in an observational study (not involving drugs, vaccines, or medical devices) was acceptable;
* Medical conditions or treatments contraindicating IM vaccination due to increased risk of bleeding. These included known bleeding disorders (such as thrombocytopenia), or treatment with anticoagulants (such as warfarin) in the 3 weeks preceding vaccination. Antiplatelet agents such as low-dose aspirin, ticlopidine (Ticlid) and clopidogrel (Plavix) were permitted;
* Evidence or history (within the previous 12 months) of drug or alcohol abuse;
* Study personnel or immediate family members (brother, sister, child, parent), the spouse of study personnel or individuals who were financially or emotionally dependent on study staff;
* Participated in this study in a prior season, if applicable; or
* Any clinical condition that, in the opinion of the investigator, may have interfered with the results of the study or pose additional risk to the subject due to participation in the study.

Primary outcomes:
measure: Primary Efficacy: First Occurrence of Either RT-PCR- or Culture-confirmed Influenza (Time-to-event Analyses) Due to Any Influenza Type A or B Strain Regardless of Antigenic Match to the Strains Selected for the Seasonal Vaccine in Subjects ≥2 to <18 Years
timeFrame: Day 14 to Day 180 or until the end of the influenza season, whichever is longer
measure: Co-Primary: First Occurrence of Either RT-PCR- or Culture-confirmed Influenza (Time-to-event Analyses) Due to Any Influenza Type A or B Strain Regardless of Antigenic Match to the Strains Selected for the Seasonal Vaccine in Subjects ≥3 to <18 Years
timeFrame: Day 14 to Day 180 or until the end of the influenza season, whichever is longer
Secondary outcomes:
measure: Secondary Efficacy #1: First Occurrence of Either RT-PCR- or Culture-confirmed Influenza Due to Any Influenza Type A or B Strain Regardless of Antigenic Match to the Strains Selected for the Seasonal Vaccine
timeFrame: Day 14 to Day 180 or until the end of the influenza season, whichever is longer.
measure: Secondary Efficacy #2: First Occurrence of RT-PCR-confirmed Influenza Due to Any Influenza Type A or B Strain Regardless of Antigenic Match to the Strains Selected for the Seasonal Vaccine
timeFrame: Day 14 to Day 180 or until the end of the influenza season, whichever is longer.
measure: Secondary Efficacy #3: First Occurrence of Culture-confirmed Influenza Due to Any Influenza Type A or B Strain Regardless of Antigenic Match to the Strains Selected for the Seasonal Vaccine
timeFrame: Day 14 to Day 180 or until the end of the influenza season, whichever is longer.
measure: Secondary Efficacy #4: First Occurrence of Culture-confirmed Influenza Due to Influenza Type A or B Strain Antigenically Matched to the Strains Selected for the Seasonal Vaccine
timeFrame: Day 14 to Day 180 or until the end of the influenza season, whichever is longer.
measure: Secondary Immunogenicity: Geometric Mean Titers for 4 Influenza Strains (HI Assay)
timeFrame: Day 1 (all subjects), Day 22 (all previously vaccinated subjects) or Day 29 and Day 50 (all not previously vaccinated subjects receiving 2 doses)
measure: ISecondary Immunogenicity: Percentage of Subjects Achieving Seroconversion for 4 Influenza Strains (HI Assay)
timeFrame: Day 22 (all previously vaccinated subjects) or Day 29 and Day 50 (all not previously vaccinated subjects)
measure: Secondary Immunogenicity: Geometric Mean Ratio for 4 Influenza Strains (HI Assay)
timeFrame: Day 22/Day 1 (all previously vaccinated subjects) or Day 29/Day 1 and Day 50/Day 1 (all not previously vaccinated subjects receiving 2 doses)
measure: Secondary Immunogenicity: Percentage of Subjects With HI Titer ≥1:40 for All 4 Influenza Strains (HI Assay)
timeFrame: Day 1 (all subjects), Day 22 (all "previously vaccinated" subjects receiving a single vaccine dose) or Days 29 and 50 (all "not previously vaccinated"subjects receiving 2 doses)
measure: Safety: Percentage of Subjects With Solicited Local and Systemic Adverse Events for 7 Days After Vaccination
timeFrame: days after vaccination on Day 1 (for "previously vaccinated" subjects) or for 7 days after vaccination on Day 1 and Day 29 (for "not previously vaccinated" subjects)
measure: Safety: Percentage of Subjects With Unsolicited AEs for 21 Days After Vaccination
timeFrame: Day 1 to Day 22 (for previously vaccinated subjects) or Day 1 to Day 50 (for not previously vaccinated subjects)
measure: Safety: Subjects With SAEs, AEs Leading to Withdrawal From Vaccination and/or the Study,(MAAEs) Within 30 Days of a 1st Occurrence, Post-ILI, and NOCDs Reported During Entire Study Participation or End of Flue Season, Whichever Was Longer
timeFrame: Day 1 to Day 181 (for previously vaccinated subjects) or to Day 209 (for not previously vaccinated subjects)
Other outcomes:
Locations:
city: Sherwood
country: Australia
facility: 302 AusTrials Pty Ltd
state: Queensland
city: Carlton
country: Australia
facility: 300 Murdoch Childrens Research Institute
state: Victoria
city: Tallinn
country: Estonia
facility: 500 Merelahe Family Doctors Centre
state: Harjumaa
city: Tallinn
country: Estonia
facility: 504 Merekivi Family Doctors Ltd
state: Harjumaa
city: Tallinn
country: Estonia
facility: 502 Medicum AS
state: Harjumaa
city: Paide
country: Estonia
facility: 503 Vee Family Doctors Centre
state: Järvamaa
city: Tartu
country: Estonia
facility: 505 Clinical Research Center
state: Tartumaa
city: Tartu
country: Estonia
facility: 505 Clinical Research Center
city: Espoo
country: Finland
facility: 607 Espoo Vaccine Research Clinic
city: Helsinki
country: Finland
facility: 603 Helsinki South Vaccine Research Clinic
city: Helsinki
country: Finland
facility: 604 Helsinki South Vaccine Research Clinic
city: Järvenpää
country: Finland
facility: 600 Järvenpää Vaccine Research Clinic
city: Kokkola
country: Finland
facility: 606 Kokkola Vaccine Research Clinic
city: Oulu
country: Finland
facility: 605 Oulu Vaccine Research Clinic
city: Pori
country: Finland
facility: 601 Pori Vaccine Research Clinic
city: Seinäjoki
country: Finland
facility: 602 Seinäjoki Vaccine Research Clinic
city: Tampere
country: Finland
facility: 608 Tampere Vaccine Research Clinic
city: Turku
country: Finland
facility: 609 Turku Vaccine Research Clinic
city: Alytus
country: Lithuania
facility: 706 Private Office of Children Pulmonologist
state: Alytus Apskritis
city: Kaunas
country: Lithuania
facility: 704 Kauno klinikine ligonine
state: Kauno Apskritis
city: Kaunas
country: Lithuania
facility: 703 UAB InMedica
state: Kauno Apskritis
city: Kaunas
country: Lithuania
facility: 702 JSC Saules seimos medicinos centras
state: Kauno Apskritis
city: Kaunas
country: Lithuania
facility: 700 Kaunas Silainiai Outpatient Clinic
state: Kauno Apskrits
city: Vilnius
country: Lithuania
facility: 701 Naujininkai Outpatient Clinic
state: Vilnaius Apskritis
city: Dasmarinas
country: Philippines
facility: 402 De La Salle Health Sciences Institute
state: Cavite
city: Dasmarinas
country: Philippines
facility: 405 De La Salle Health Sciences Institute
state: Cavite
city: Manila
country: Philippines
facility: 403 Philippine General Hospital
state: National Capital Region
city: Manila
country: Philippines
facility: 404 Philippine General Hospital
state: National Capital Region
city: Muntinlupa
country: Philippines
facility: 400 Research Institute For Tropical Medicine
state: National Capital Region
city: Muntinlupa
country: Philippines
facility: 401 Research Institute For Tropical Medicine
state: National Capital Region
city: Muntinlupa
country: Philippines
facility: 406 Research Institute For Tropical Medicine
state: National Capital Region
city: Trzebnica
country: Poland
facility: 803 Szpital im. Sw. Jadwigi Slaskiej w Trzebnicy
state: Dolnoslaskie
city: Bydgoszcz
country: Poland
facility: 805 Szpital Uniwersytecki nr 2 im. dr. Jana Biziela w Bydgoszczy
state: Kujawsko-pomorskie
city: Leczna
country: Poland
facility: 800 Niepubliczny Zaklad Opieki Zdrowotnej (NZOZ) "Salmed" s. c.
state: Lubelskie
city: Tarnow
country: Poland
facility: 806 Specjalistyczny Szpital im. E. Szczeklika w Tarnowie
state: Malopolskie
city: Debica
country: Poland
facility: 804 Prywatny Gabinet Lekarski
state: Podkarpackie
city: Siemianowice Slaskie
country: Poland
facility: NZLA Michalkowice - Jarosz i Partnerzy Spolka Lekarska
state: Slaskie
city: Santiago de Compostela
country: Spain
facility: 900 Complejo Hospitalario Universitario de Santiago
state: A Coruña
city: Khon Kaen
country: Thailand
facility: 200 Srinagarind Hospital, Khon Kaen University
state: Muang
city: Chiang Mai
country: Thailand
facility: 201 ChiangMai University
Study officials:
affiliation: Seqirus
name: Clinical Program Director
role: STUDY_DIRECTOR
References:
citation: Nolan T, Fortanier AC, Leav B, Poder A, Bravo LC, Szymanski HT, Heeringa M, Vermeulen W, Matassa V, Smolenov I, Edelman JM. Efficacy of a Cell-Culture-Derived Quadrivalent Influenza Vaccine in Children. N Engl J Med. 2021 Oct 14;385(16):1485-1495. doi: 10.1056/NEJMoa2024848.