Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of QIVc in Subjects ≥2 to <18 Years of Age
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT03165617 |
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Recruitment Status :
Completed
First Posted : May 24, 2017
Results First Posted : October 22, 2020
Last Update Posted : October 22, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Influenza, Human | Biological: QIVc Biological: Non-influenza Comparator Vaccine | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 4514 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Intervention Model Description: | Phase 3/4 |
| Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
| Primary Purpose: | Prevention |
| 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 |
| Actual Study Start Date : | May 25, 2017 |
| Actual Primary Completion Date : | September 30, 2019 |
| Actual Study Completion Date : | September 30, 2019 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: QIVc (≥2 years to <18 Years of Age)
Cell-derived Seasonal Quadrivalent Influenza Vaccine
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Biological: QIVc
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
Other Name: Flucelvax Quadrivalent |
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Active Comparator: Non-Influenza Comparator Vaccine
Non-Influenza Comparator Vaccine
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Biological: Non-influenza Comparator Vaccine
Non-influenza comparator vaccine for intramuscular use |
- 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 [ Time Frame: Day 14 to Day 180 or until the end of the influenza season, whichever is longer ]
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%.
- 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 [ Time Frame: Day 14 to Day 180 or until the end of the influenza season, whichever is longer ]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
- 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 [ Time Frame: Day 14 to Day 180 or until the end of the influenza season, whichever is longer. ]
The 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 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 in subjects 2 to <18 years, 2 to <9 years, 4 to <18 years, and 9 to <18 years.
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.
- 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 [ Time Frame: Day 14 to Day 180 or until the end of the influenza season, whichever is longer. ]
The endpoint was defined as the time from the last study vaccination to the onset of the 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, that occurred more than 14 days after the last vaccination until the end of the influenza season in subjects 2 to <18 years, 2 to <9 years, 4 to <18 years, and 9 to <18 years
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.
- 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 [ Time Frame: Day 14 to Day 180 or until the end of the influenza season, whichever is longer. ]
The secondary endpoint was defined as the time from the last study vaccination to the onset of the 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, that occurred more than 14 days after the last vaccination until the end of the influenza season in subjects 2 to <18 years, 2 to <9 years, 4 to <18 years, and 9 to <18 years.
Dataset used: FAS Efficacy
- 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 [ Time Frame: Day 14 to Day 180 or until the end of the influenza season, whichever is longer. ]The endpoint was defined as the time from the last study vaccination to the onset of the first occurrence of culture-confirmed influenza due to influenza Type A or B strain antigenically matched 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 in subjects 2 to <18 years, 2 to <9 years, 4 to <18 years, and 9 to <18 years.
- Secondary Immunogenicity: Geometric Mean Titers for 4 Influenza Strains (HI Assay) [ Time Frame: Day 1 (all subjects), Day 22 (all previously vaccinated subjects) or Day 29 and Day 50 (all not previously vaccinated subjects receiving 2 doses) ]Immunogenicity was characterized by HI assay 3 weeks after the last vaccination in a subset of subjects 2 to <9 years of age enrolled in Season 2 (n=432) and Season 3 (n=319) who were immunized and had immunogenicity data at the assessed timepoints (FAS Immunogenicity). Immunogenicity was assessed at baseline (Day 1; all subjects in immunogenicity subset), at Day 22 (all "previously vaccinated" subjects receiving a single dose of the study vaccine), and at Days 29 and 50 (all "not previously vaccinated" subjects receiving 2 doses) for all 4 influenza strains using the HI assay.
- ISecondary Immunogenicity: Percentage of Subjects Achieving Seroconversion for 4 Influenza Strains (HI Assay) [ Time Frame: Day 22 (all previously vaccinated subjects) or Day 29 and Day 50 (all not previously vaccinated subjects) ]
Immunogenicity was characterized by HI assay 3 weeks after the last vaccination in a subset of subjects 2 to <9 years of age enrolled in Season 2 (n=432) and Season 3 (n=319) who were immunized and had immunogenicity data at the assessed timepoints (FAS Immunogenicity). Immunogenicity was assessed at baseline (Day 1; all subjects in immunogenicity subset), at Day 22 (all "previously vaccinated" subjects receiving a single dose of the study vaccine), and at Days 29 and 50 (all "not previously vaccinated" subjects receiving 2 doses) for all 4 influenza strains using the HI assay.
Seroconversion was defined as: 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)
Dataset used: FAS Immunogenicity = All subjects in the All Enrolled Set who received at least one dose of study vaccine and provided evaluable serum samples at both baseline and after the last vaccination.
- Secondary Immunogenicity: Geometric Mean Ratio for 4 Influenza Strains (HI Assay) [ Time Frame: 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) ]
Immunogenicity was characterized by HI assay 3 weeks after the last vaccination in a subset of subjects 2 to <9 years of age enrolled in Season 2 (n=432) and Season 3 (n=319) who were immunized and had immunogenicity data at the assessed timepoints (FAS Immunogenicity). Immunogenicity was assessed at baseline (Day 1; all subjects in immunogenicity subset), at Day 22 (all "previously vaccinated" subjects receiving a single dose of the study vaccine), and at Days 29 and 50 (all "not previously vaccinated" subjects receiving 2 doses) for all 4 influenza strains using the HI assay.
Geometric mean ratios (GMRs) measure the ratio in immunogenicity titers within subject\
Dataset used: FAS Immunogenicity = All subjects in the All Enrolled Set who received at least one dose of study vaccine and provided evaluable serum samples at both baseline and after the last vaccination.
- Secondary Immunogenicity: Percentage of Subjects With HI Titer ≥1:40 for All 4 Influenza Strains (HI Assay) [ Time Frame: 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) ]
Immunogenicity was characterized by HI assay 3 weeks after the last vaccination in a subset of subjects 2 to <9 years of age enrolled in Season 2 (n=432) and Season 3 (n=319) who were immunized and had immunogenicity data at the assessed timepoints (FAS Immunogenicity). Immunogenicity was assessed at baseline (Day 1; all subjects in immunogenicity subset), at Day 22 (all "previously vaccinated" subjects receiving a single dose of the study vaccine), and at Days 29 and 50 (all "not previously vaccinated" subjects receiving 2 doses) for all 4 influenza strains using the HI assay.
The measures for assessing immunogenicity as determined by HI were as follows: Percentage of subjects with an HI titer ≥1:40 on Day 22 (all "previously vaccinated" subjects receiving a single vaccine dose) or Days 29 and 50 (all "not previously vaccinated" subjects receiving 2 doses) for all 4 influenza strains
- Safety: Percentage of Subjects With Solicited Local and Systemic Adverse Events for 7 Days After Vaccination [ Time Frame: 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) ]
The measures for assessing safety and tolerability were as follows: Percentage of subjects with solicited local and systemic adverse events (AEs) for 7 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) in the QIVc group and the non-influenza comparator vaccine group.
Dataset used: Solicited Safety Set
- Safety: Percentage of Subjects With Unsolicited AEs for 21 Days After Vaccination [ Time Frame: Day 1 to Day 22 (for previously vaccinated subjects) or Day 1 to Day 50 (for not previously vaccinated subjects) ]
The measures for assessing safety and tolerability were as follows: Percentage of subjects with unsolicited AEs assessed from Day 1 to Day 22 (for "previously vaccinated" subjects) or from Day 1 to Day 50 (for "not previously vaccinated" subjects) in the QIVc group and the non-influenza comparator vaccine group.
Dataset used: Unsolicited Safety Set (Unsolicited Adverse Events)
- 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 [ Time Frame: Day 1 to Day 181 (for previously vaccinated subjects) or to Day 209 (for not previously vaccinated subjects) ]
The measures for assessing safety and tolerability were as follows: Percentage of subjects with SAEs, AEs leading to withdrawal from vaccination and/or the study, Medically-Attended AEs (MAAEs) within 30 days after the first occurrence of an ILI, and New Onset of Chronic Diseases (NOCDs) reported during the subject's entire participation in the study (ie, from Day 1 to Day 181 [for "previously vaccinated" subjects] or from Day 1 to Day 209 [for "not previously vaccinated" subjects]), or until the end of influenza season, whichever was longer, and all medications associated with these events.
Dataset used: Overall Safety Set
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| Ages Eligible for Study: | 2 Years to 17 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03165617
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| Study Director: | Clinical Program Director | Seqirus |
Documents provided by Seqirus:
| Responsible Party: | Seqirus |
| ClinicalTrials.gov Identifier: | NCT03165617 |
| Other Study ID Numbers: |
V130_12 2016-002883-15 ( EudraCT Number ) |
| First Posted: | May 24, 2017 Key Record Dates |
| Results First Posted: | October 22, 2020 |
| Last Update Posted: | October 22, 2020 |
| Last Verified: | October 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Seqirus supports the release of anonymized subject-level and study-level data in compliance with regulatory requirements, including Clinical Documents which are part of the CTD modules submitted to regulatory agencies for public release. Summary results disclosure is either in document form (e.g., ICH E3 Clinical Study Report synopsis) or structured data form (such as summary results in ClinicalTrials.gov (United States) or eudract.ema.europa.eu (EU Clinical Trial Registry [EU CTR]). |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (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 |
| URL: | https://www.seqirus.com/partnering |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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Influenza vaccine |
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Influenza, Human Respiratory Tract Infections Infections Orthomyxoviridae Infections |
RNA Virus Infections Virus Diseases Respiratory Tract Diseases |