Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of QIVc in Subjects ≥2 to <18 Years of Age

NCT03165617 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: V130_122016-002883-15
• Study Type: interventional
• Target: 4,514
• Locations: 7 countries
• Sites: 34

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

Conditions

Influenza, Human

Keywords

Influenza vaccine

Outcome Measures

Primary Outcomes (2)

• 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

  The primary efficacy endpoint was defined as the time from the last study vaccination to the onset of the 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, that occurred more than 14 days after the last vaccination until the end of the influenza season. Dataset Used: FAS-Efficacy = All subjects in the All Enrolled Set who received at least one dose of study vaccine and were evaluated for efficacy from 14 days after the last vaccination. The success criterion used for this primary objective was as follows: The efficacy of the QIVc was demonstrated if the lower limit (LL) of the 2-sided 95% confidence interval (CI) for VE was above 20%.

  Day 14 to Day 180 or until the end of the influenza season, whichever is longer

• 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

  The co-primary efficacy endpoint: was defined as the time from the last study vaccination to the onset of the 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, that occurred more than 14 days after the last vaccination until the end of the influenza season.Absolute vaccine efficacy of QIVc by first occurrence RT-PCR or culture confirmed influenza, due to any influenza Type A and B strain in subjects ≥3 years to \<18 years of age

  Day 14 to Day 180 or until the end of the influenza season, whichever is longer

Secondary Outcomes (11)

• 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

  Day 14 to Day 180 or until the end of the influenza season, whichever is longer.

• 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

  Day 14 to Day 180 or until the end of the influenza season, whichever is longer.

• 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

  Day 14 to Day 180 or until the end of the influenza season, whichever is longer.

• 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

  Day 14 to Day 180 or until the end of the influenza season, whichever is longer.

• Secondary Immunogenicity: Geometric Mean Titers for 4 Influenza Strains (HI Assay)

  Day 1 (all subjects), Day 22 (all previously vaccinated subjects) or Day 29 and Day 50 (all not previously vaccinated subjects receiving 2 doses)

Study Arms (2)

QIVc (≥2 years to <18 Years of Age)

EXPERIMENTAL

Cell-derived Seasonal Quadrivalent Influenza Vaccine

Biological: QIVc

Non-Influenza Comparator Vaccine

ACTIVE COMPARATOR

Non-Influenza Comparator Vaccine

Biological: Non-influenza Comparator Vaccine

Interventions

QIVc BIOLOGICAL

Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains

Also known as: Flucelvax Quadrivalent

QIVc (≥2 years to <18 Years of Age)

Non-influenza Comparator Vaccine BIOLOGICAL

Non-influenza comparator vaccine for intramuscular use

Non-Influenza Comparator Vaccine

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Seqirus: lead

Study Sites (40)

302 AusTrials Pty Ltd

Sherwood, Queensland, 4075, Australia

Location

300 Murdoch Childrens Research Institute

Carlton, Victoria, 3010, Australia

Location

500 Merelahe Family Doctors Centre

Tallinn, Harju, 10617, Estonia

Location

504 Merekivi Family Doctors Ltd

Tallinn, Harju, 10617, Estonia

Location

502 Medicum AS

Tallinn, Harju, 13619, Estonia

Location

503 Vee Family Doctors Centre

Paide, Järvamaa, 72713, Estonia

Location

505 Clinical Research Center

Tartu, Tartu, 50106, Estonia

Location

505 Clinical Research Center

Tartu, Estonia

Location

607 Espoo Vaccine Research Clinic

Espoo, Finland

Location

603 Helsinki South Vaccine Research Clinic

Helsinki, Finland

Location

604 Helsinki South Vaccine Research Clinic

Helsinki, Finland

Location

600 Järvenpää Vaccine Research Clinic

Jarvenpaa, Finland

Location

606 Kokkola Vaccine Research Clinic

Kokkola, 67100, Finland

Location

605 Oulu Vaccine Research Clinic

Oulu, Finland

Location

601 Pori Vaccine Research Clinic

Pori, Finland

Location

602 Seinäjoki Vaccine Research Clinic

Seinäjoki, Finland

Location

608 Tampere Vaccine Research Clinic

Tampere, Finland

Location

609 Turku Vaccine Research Clinic

Turku, Finland

Location

706 Private Office of Children Pulmonologist

Alytus, Alytus Apskritis, 62142, Lithuania

Location

704 Kauno klinikine ligonine

Kaunas, Kaunas County, 47116, Lithuania

Location

703 UAB InMedica

Kaunas, Kaunas County, 48259, Lithuania

Location

702 JSC Saules seimos medicinos centras

Kaunas, Kaunas County, 49449, Lithuania

Location

700 Kaunas Silainiai Outpatient Clinic

Kaunas, Kauno Apskrits, 48259, Lithuania

Location

701 Naujininkai Outpatient Clinic

Vilnius, Vilnaius Apskritis, 02169, Lithuania

Location

402 De La Salle Health Sciences Institute

Dasmariñas, Cavite, 4114, Philippines

Location

405 De La Salle Health Sciences Institute

Dasmariñas, Cavite, 4114, Philippines

Location

403 Philippine General Hospital

Manila, National Capital Region, 1000, Philippines

Location

404 Philippine General Hospital

Manila, National Capital Region, 1000, Philippines

Location

400 Research Institute For Tropical Medicine

Muntinlupa, National Capital Region, 1781, Philippines

Location

401 Research Institute For Tropical Medicine

Muntinlupa, National Capital Region, 1781, Philippines

Location

406 Research Institute For Tropical Medicine

Muntinlupa, National Capital Region, 1781, Philippines

Location

805 Szpital Uniwersytecki nr 2 im. dr. Jana Biziela w Bydgoszczy

Bydgoszcz, Kuyavian-Pomeranian Voivodeship, 85-168, Poland

Location

806 Specjalistyczny Szpital im. E. Szczeklika w Tarnowie

Tarnów, Lesser Poland Voivodeship, 33-100, Poland

Location

803 Szpital im. Sw. Jadwigi Slaskiej w Trzebnicy

Trzebnica, Lower Silesian Voivodeship, 55-100, Poland

Location

800 Niepubliczny Zaklad Opieki Zdrowotnej (NZOZ) "Salmed" s. c.

Łęczna, Lublin Voivodeship, 21-010, Poland

Location

804 Prywatny Gabinet Lekarski

Dębica, Podkarpackie Voivodeship, 39-200, Poland

Location

NZLA Michalkowice - Jarosz i Partnerzy Spolka Lekarska

Siemianowice Śląskie, Silesian Voivodeship, 41-103, Poland

Location

900 Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, A Coruña, 15706, Spain

Location

200 Srinagarind Hospital, Khon Kaen University

Khon Kaen, Muang, 40002, Thailand

Location

201 ChiangMai University

Chiang Mai, 50200, Thailand

Location

Related Publications (1)

• 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.

  PMID: 34644472 DERIVED

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Seqirus Clinical Trial Manager
• Organization: Seqirus

seqirus.clinicaltrials@Seqirus.com

1-855-358-8966

Study Officials

• Clinical Program Director

  Seqirus

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 3/4

Study Record Dates

• First Submitted: May 17, 2017
• First Posted: May 24, 2017
• Study Start: May 25, 2017
• Primary Completion: September 30, 2019
• Study Completion: September 30, 2019
• Last Updated: October 22, 2020
• Results First Posted: October 22, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Seqirus aims to disclose these results from clinical studies within twelve (12) months of the Study Completion unless otherwise mandated by local law or regulation.
• Access Criteria: All requests will be fully vetted and data to be released approved, prior to distribution. Seqirus does not release subject-level data and study-level data if the requester's purpose is to conduct a re-analysis of the study data, as opposed to a meta-analysis. While the URL link below does not outline the data sharing policy per se, it does present a high-level view of how the organization partners with external collaborators

Locations

ES (1); PH (7); TH (2); AU (2); PL (6); FI (10); LI (6)