A Study to Evaluate the Immunogenicity and Safety of Seqirus Quadrivalent Influenza Vaccine (QIV) in a Pediatric Population 5 Through 17 Years of Age

A Phase 3, Randomized, Multicenter, Observer-Blinded, Noninferiority Study to Evaluate the Immunogenicity and Safety of a Seqirus Quadrivalent Inactivated Influenza Virus Vaccine (Seqirus QIV) With a US-Licensed 2015-2016 Quadrivalent Inactivated Comparator Influenza Vaccine (Comparator QIV) in a Pediatric Population 5 Through 17 Years of Age

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02545543

Enrollment

2278

Registered

2015-09-10

Start date

2015-09-30

Completion date

2016-06-30

Last updated

2018-05-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Influenza, Human

Brief summary

This is a study to assess the immune (antibody) response and safety of a Seqirus split virion, inactivated Quadrivalent Influenza Vaccine (Seqirus QIV), in comparison with a US licensed 2015/2016 Quadrivalent Influenza Vaccine (comparator QIV) in a healthy pediatric population 5 through 17 years of age.

Interventions

BIOLOGICALSeqirus QIV

Seqirus QIV, inactivated, split-virion, thimerosal-free, quadrivalent influenza vaccine, administered as a 0.5 mL intramuscular dose. The vaccine is presented in a prefilled needleless syringe. The subject's age and influenza vaccination history determines the dosing regimen (a single vaccination or a 2-vaccination regimen administered 28 days apart) according to the most recent US ACIP guidelines for seasonal influenza vaccination.

BIOLOGICALComparator QIV

The US-licensed Comparator QIV, inactivated, split-virion, thimerosal-free, quadrivalent influenza vaccine, administered as a 0.5 mL intramuscular dose. The vaccine is presented in a prefilled needleless syringe. The subject's age and influenza vaccination history determines the dosing regimen (a single vaccination or a 2-vaccination regimen administered 28 days apart) according to the most recent US ACIP guidelines for seasonal influenza vaccination.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

5 Years to 17 Years

Healthy volunteers

Yes

Inclusion criteria

* Males or females 5 through 17 years of age on the day of first study vaccination. * Parent or legally acceptable representative able to provide written informed consent and be willing and able to adhere to all protocol requirements including blood draws. Participant assent will also be obtained if required. * If applicable, females of childbearing potential (ie, ovulating, not surgically sterile) must be abstinent or be willing to use a medically accepted contraceptive regimen until at least 28 days after the last Study Vaccine. Females of childbearing potential must return a negative urine pregnancy test result, prior to any vaccination dose with the Study Vaccine.

Exclusion criteria

* History of allergic reactions to egg proteins or any components of the Study Vaccines. * History of serious adverse reactions to any influenza vaccines. * History of Guillain-Barré syndrome or other demyelinating disease. * History of licensed or investigational influenza vaccination in the last 6 months. * Clinical signs of active infection and/or an oral temperature of ≥ 100°F (37.8°C) on the day of planned Study Vaccine administration or within 48 hours preceding vaccination. * Current or recent, acute or chronic medical conditions that in the opinion of the Investigator are clinically significant and/or unstable (such as illness exacerbations) within the preceding 30 days. * History of any seizures, with the exception of a single febrile seizure. * Self-reported or known seropositivity suggestive of acute or chronic viral infection for human immunodeficiency virus, hepatitis B or hepatitis C. * Known or suspected congenital or acquired immunosuppressive conditions. * Current or recent immunosuppressive or immunomodulatory therapy, as follows: * Chronic or long-term systemic corticosteroids: ≥ 0.125 mg/kg/day of oral prednisolone or equivalent daily; * Sporadic systemic corticosteroids: ≥ 0.5 mg/kg/day of oral prednisolone or equivalent for two or more short courses of \> 3 days in the 3 months preceding vaccination; * Antineoplastic chemotherapy or radiation therapy within the 6 months preceding vaccination. Note: Use of topical, inhalant or localised tissue injections of corticosteroids prior to administration of the Study Vaccine or throughout the study are acceptable. * Administration of immunoglobulin and/or any blood products within the 3 months preceding vaccination, or planned administration during the study. * Participation in a clinical trial or use of an investigational compound within 28 days prior to the first dose of Study Vaccine, or within 28 days after receiving the final indicated dose of Study Vaccine, or plans to enter a study during this period. * Vaccination with a licensed vaccine 28 days (for live or inactivated vaccines) prior to receiving the first dose of Study Vaccine, or plans to receive any licensed vaccine prior to the Study Exit Visit. * Pregnant or lactating females.

Design outcomes

Primary

Measure	Time frame	Description
The Geometric Mean Titer (GMT) Ratio of Each Virus Strain.	28 days after last vaccination.	Noninferiority of Seqirus QIV compared to comparator QIV was assessed by the eight co-primary endpoints of hemagglutination inhibition (HI) antibody geometric mean titer (GMT) and seroconversion rate (SCR) for each viral strain included in the vaccines. The GMT ratio is defined as the geometric mean of the postvaccination HI titer for the US-licensed comparator QIV over the geometric mean of the postvaccination HI titer for Seqirus QIV.
The Difference in Seroconversion Rate (SCR) for Each Virus Strain.	28 days after last vaccination.	Noninferiority of Seqirus QIV compared to Comparator QIV was assessed by the eight co-primary endpoints of HI geometric mean titer (GMT) and seroconversion rate (SCR) for each viral strain. The rate of 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. For the SCR comparison, the difference between the SCR for each virus strain will be determined.

Secondary

Measure	Time frame	Description
Safety Endpoint: The Frequency of Cellulitis-like Reaction.	28 days after each vaccination.	Frequency of cellulitis-like reaction for at least 28 days after each vaccination dose
Safety Endpoint: The Frequency and Severity of Unsolicited Adverse Events (AEs).	28 days after each vaccination.	Frequency and severity of unsolicited AEs for at least 28 days (ie, day of vaccination and 27 subsequent days) after each vaccination dose
Safety Endpoint: The Frequency of Serious Adverse Events (SAEs).	180 days after the last vaccination dose.	Frequency of serious adverse events (SAEs) for 180 days after the last vaccination dose.
Safety Endpoint: The Frequency and Severity of Solicited Local Adverse Reactions.	7 days after each vaccination.	Frequency and severity of solicited local adverse reactions (AEs) for 7 days (ie, day of vaccination and 6 subsequent days) after each vaccination dose
Immunogenicity Endpoint: Seroconversion Rate (SCR)	28 days after last vaccination.	The humoral immune response was assessed for Seqirus QIV & comparator QIV. Serum HI titers against the 4 influenza vaccine strains was used to calculate: \- SCRs: % of subjects with either a prevaccination HI titer \< 1:10 and a postvaccination HI titer ≥ 1:40 or a prevaccination titer ≥ 1:10 and a ≥ 4-fold increase in postvaccination titer
Immunogenicity Endpoint: Seroprotection Rate	28 days after last vaccination.	The humoral immune response was assessed for Seqirus QIV & comparator QIV. Serum HI titers against the 4 influenza vaccine strains was used to calculate: \- The % of subjects with a titer ≥40 (seroprotection rates) at Day 1 and at Exit Visit
Immunogenicity Endpoint: Geometric Mean Fold Increase (GMFI)	28 days after last vaccination.	The humoral immune response was assessed for Seqirus QIV & comparator QIV. Serum HI titers against the 4 influenza vaccine strains was used to calculate: \- Geometric mean fold increase (GMFI): geometric mean fold titer rise from Day 1 to Exit Visit
Immunogenicity Endpoint: GMTs - Geometric Mean of HI Titers Prevaccination (Day 1) and Postvaccination (Study Exit Visit)	28 days after last vaccination.	The humoral immune response was assessed for Seqirus QIV & comparator QIV. Serum HI titers against the 4 influenza vaccine strains was used to calculate: \- Geometric mean of HI titers prevaccination & postvaccination
Safety Endpoint: The Frequency and Severity of Solicited Systemic Adverse Events (AEs).	7 days after each vaccination.	Frequency and severity of solicited systemic adverse events (AEs) for 7 days (ie, day of vaccination and 6 subsequent days) after each vaccination dose

Countries

United States

Participant flow

Recruitment details

First Patient In: 14-SEP-2015, Last Patient Last Visit: 13-JUN-2016. Number of activated sites that enrolled subjects: 32 (all based in USA).

Pre-assignment details

Number of subjects screened: 2349. Number of subjects randomized: 2278

Participants by arm

Arm	Count
Seqirus Quadrivalent Influenza Vaccine The Seqirus study vaccine is a sterile, thimerosal-free suspension containing 60 mcg total hemagglutinin antigen per 0.5 mL dose (15 mcg each of the four recommended influenza strains for the Northern Hemisphere 2015/2016 influenza season). Seqirus QIV: Seqirus QIV, inactivated, split-virion, thimerosal-free, quadrivalent influenza vaccine, administered as a 0.5 mL intramuscular dose. The vaccine is presented in a prefilled needleless syringe. The subject's age and influenza vaccination history determines the dosing regimen (a single vaccination or a 2-vaccination regimen administered 28 days apart) according to the most recent US ACIP guidelines for seasonal influenza vaccination.	1,709
Comparator Quadrivalent Influenza Vaccine The comparator Quadrivalent Inactivated Influenza vaccine is a US-licensed product containing four recommended influenza strains for the Northern Hemisphere 2015/2016 influenza season. Comparator QIV: The US-licensed Comparator QIV, inactivated, split-virion, thimerosal-free, quadrivalent influenza vaccine, administered as a 0.5 mL intramuscular dose. The vaccine is presented in a prefilled needleless syringe. The subject's age and influenza vaccination history determines the dosing regimen (a single vaccination or a 2-vaccination regimen administered 28 days apart) according to the most recent US ACIP guidelines for seasonal influenza vaccination.	569
Total	2,278

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Enrolment of subject at >1 study site	1	1
Overall Study	Lost to Follow-up	67	25
Overall Study	Noncomplaince	1	0
Overall Study	Physician Decision	3	0
Overall Study	Withdrawal by Subject	9	8

Baseline characteristics

Characteristic	Seqirus Quadrivalent Influenza Vaccine	Comparator Quadrivalent Influenza Vaccine	Total
Age, Continuous	9.5 years STANDARD_DEVIATION 3.49	9.5 years STANDARD_DEVIATION 3.46	9.5 years STANDARD_DEVIATION 3.48
Age, Customized 5 through 8 years	875 Participants	291 Participants	1166 Participants
Age, Customized 9 through 17 years	834 Participants	278 Participants	1112 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	412 Participants	130 Participants	542 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1293 Participants	438 Participants	1731 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	4 Participants	1 Participants	5 Participants
Race (NIH/OMB) American Indian or Alaska Native	5 Participants	2 Participants	7 Participants
Race (NIH/OMB) Asian	16 Participants	2 Participants	18 Participants
Race (NIH/OMB) Black or African American	359 Participants	113 Participants	472 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	13 Participants	2 Participants	15 Participants
Race (NIH/OMB) Unknown or Not Reported	77 Participants	20 Participants	97 Participants
Race (NIH/OMB) White	1239 Participants	430 Participants	1669 Participants
Region of Enrollment United States	1709 participants	569 participants	2278 participants
Sex: Female, Male Female	825 Participants	267 Participants	1092 Participants
Sex: Female, Male Male	884 Participants	302 Participants	1186 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	1,019 / 1,692	319 / 560
serious Total, serious adverse events	8 / 1,692	2 / 560

Outcome results

Primary

The Difference in Seroconversion Rate (SCR) for Each Virus Strain.

Noninferiority of Seqirus QIV compared to Comparator QIV was assessed by the eight co-primary endpoints of HI geometric mean titer (GMT) and seroconversion rate (SCR) for each viral strain. The rate of 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. For the SCR comparison, the difference between the SCR for each virus strain will be determined.