Immunogenicity and Safety of Quadrivalent Influenza Vaccine (NBP607-QIV) in Adults and Elderly Subjects

A Multi-center, Randomized, Double-blind Phase III Clinical Trial to Assess the Immunogenicity and Safety of Quadrivalent Inactivated Cell Culture-derived Influenza Vaccine in Adults and Elderly Subjects

All participants received a single dose of their assigned vaccine on Day 0. They were followed up for immunogenicity and safety through Day 21 post-vaccination. Serious adverse events were collected for 6 months post-vaccination.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: NBP607-QIV; Biological: NBP607-Y; Biological: NBP607-V

Detailed Description

In a randomized controlled phase III trial undertaken in 10 university hospitals of South Korea, adults and elderly subjects were randomly assigned in a 2:1:1 ratio to NBP607-QIV versus cell culture-based trivalent inactivated influenza vaccine (TIV), NBP607-Y and NBP607-V. Immunogenicity was assessed 3 weeks after vaccination by hemagglutination inhibition (HI) assay. Safety was assessed for 6 months post-vaccination: solicited adverse events for 7 days, unsolicited adverse events (AEs) for 21 days and serious adverse events (SAE) for 6 months.

• Study Type: Interventional
• Enrollment (Actual): 1503
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults aged 19 years and older
• Those who are able to comply with the requirements for the study
• If women, a negative pregnancy test and willingness to use birth control measures for the entire study duration

Exclusion Criteria:

• Disorders in immune function
• Any malignancy or lymphoproliferative disorder
• History of Guillain-Barré syndrome
• Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time
• Experience of fever (>38.0 ℃) within 24 hours following vaccination
• Body temperature >38.0 ℃ at the vaccination day
• Concomitant medications/therapy such as immunosuppressants or immune modifying drugs, systemic corticosteroids, immunoglobulins, blood or blood- derived products within 3 months
• Influenza vaccination within 6 months
• Subjects who have participated in other interventional study within 4 weeks
• Any vaccination within 1 month
• Those who are planning to receive any vaccine within 1 month from the study vaccine
• Individuals with any serious chronic or progressive disease
• Pregnant or breast-feeding women
• Any other reason that in the opinion of the investigator might interfere with the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: NBP607-QIV; Participants aged 19 years and older received a 0.5mL single intramuscular dose of Quadrivalent Inactivated Cell Culture-derived Influenza Vaccine containing 4 virus strains; A/H1N1, A/H3N2, B/Yamagata, B/Victoria on Day 0	Biological: NBP607-QIV; Quadrivalent Inactivated Cell Culture-derived Influenza Vaccine containing 4 virus strains; A/H1N1, A/H3N2, B/Yamagata, B/Victoria
ACTIVE_COMPARATOR: NBP607-Y; Participants aged 19 years and older received a 0.5mL single intramuscular dose of Trivalent Inactivated Cell Culture-derived Influenza Vaccine containing 3 virus strains; A/H1N1, A/H3N2, B/Yamagata on Day 0	Biological: NBP607-Y; Trivalent Inactivated Cell Culture-derived Influenza Vaccine containing 3 virus strains; A/H1N1, A/H3N2, B/Yamagata
ACTIVE_COMPARATOR: NBP607-V; Participants aged 19 years and older received a 0.5mL single intramuscular dose of Trivalent Inactivated Cell Culture-derived Influenza Vaccine containing 3 virus strains; A/H1N1, A/H3N2, B/Victoria on Day 0	Biological: NBP607-V; Trivalent Inactivated Cell Culture-derived Influenza Vaccine containing 3 virus strains; A/H1N1, A/H3N2, B/Victoria

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean HI Titers (GMTs) After Vaccination in All Subjects	GMTs of anti-influenza antibodies were measured for 4 strains: A/H1N1, A/H3N2, B/Victoria, and B/Yamagata. For each A strain, the titers were made with the pooled TIV group (NBP60-Y and NBP607-V). For each A strain, the comparion was made with the pooled TIV groups (Y+V/QIV). For each B strain, the comparison was made with the corresponding TIV group(i.e. for B/Yamagata, Geometric Mean Titer Ratio (GMR) is Y/QIV).	At Day 21 post vaccination.
Seroconversion Rate (SCR) After Vaccination in All Subjects	SCR was measured for 4 strains: A/H1N1, A/H3N2, B/Victoria, and B/Yamagata. Seroconversion was defined as the proportion of subjects who met either (1) post-vaccination HI titer of ≥ 1:40 for subjects with pre-vaccination HI titer of <1:10 or (2) Four-fold increase in post-vaccination HI titer for subjects with pre-vaccination HI titer of ≥ 1:10 For each A strain, the comparion was made with the pooled TIV groups (Y+V minus QIV). For each B strain, the comparison was made with the corresponding TIV group(i.e. for B/Yamagata, Difference of SCR (Diff.SCR) is Y minus QIV).	At Day 21 post vaccination.
Seroprotection Rate (SPR) of NBP607-QIV in the Elderly Subject Aged ≥60 Years	SPR of NBP607-QIV was measured for 4 strains: A/H1N1, A/H3N2, B/Victoria, and B/Yamagata. Seroprotection was defined as the proportion of subjects whose post-vaccination HI titer increased to ≥1:40.	At Day 21 post vaccination.
Seroconversion Rate (SCR) of NBP607-QIV in the Elderly Subject Aged ≥60 Years	SCR was measured for 4 strains: A/H1N1, A/H3N2, B/Victoria, and B/Yamagata. Seroconversion was defined as the proportion of subjects who met either (1) post-vaccination HI titer of ≥ 1:40 for subjects with pre-vaccination HI titer of <1:10 or (2) Four-fold increase in post-vaccination HI titer for subjects with pre-vaccination HI titer of ≥ 1:10	At Day 21 post vaccination.
Geometric Mean Ratio (GMR) of NBP607-QIV in the Elderly Subject Aged ≥60 Years	GMR was measured for 4 strains: A/H1N1, A/H3N2, B/Victoria, and B/Yamagata. GMR was defined as the fold-rise of the geometric mean HI titer from pre- to post-vaccination.	At Day 21 post vaccination.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Geometric Mean HI Titers (GMTs) of Each B Strain After Vaccination in All Subjects	GMTs of anti-influenza antibodies were measured for B strains: B/Victoria, and B/Yamagata. For each B strain, the comparison was made with the TIV group which did not contain the correponding B strain (i.e. for B/Yamagata, Geometric Mean Titer Ratio (GMR) is V/QIV).	At Day 21 post vaccination.
Seroconversion Rate (SCR) of B Strain After Vaccination in All Subjects	SCR was measured for each B strain: B/Victoria, and B/Yamagata. Seroconversion was defined as the proportion of subjects who met either (1) post-vaccination HI titer of ≥ 1:40 for subjects with pre-vaccination HI titer of <1:10 or (2) Four-fold increase in post-vaccination HI titer for subjects with pre-vaccination HI titer of ≥ 1:10	At Day 21 post vaccination.
Seroprotection Rate (SPR) of NBP607-QIV in the Adults Aged 19 to 59 Years	SPR of NBP607-QIV was measured for 4 strains: A/H1N1, A/H3N2, B/Victoria, and B/Yamagata. Seroprotection was defined as the proportion of subjects whose post-vaccination HI titer increased to ≥1:40.	At Day 21 post vaccination.
Seroconversion Rate (SCR) of NBP607-QIV in the Adults Aged 19 to 59 Years	SCR was measured for 4 strains: A/H1N1, A/H3N2, B/Victoria, and B/Yamagata. Seroconversion was defined as the proportion of subjects who met either (1) post-vaccination HI titer of ≥ 1:40 for subjects with pre-vaccination HI titer of <1:10 or (2) Four-fold increase in post-vaccination HI titer for subjects with pre-vaccination HI titer of ≥ 1:10	At Day 21 post vaccination.
Geometric Mean Ratio (GMR) of NBP607-QIV in the Subjects Aged 19 to 59 Years	GMR was measured for 4 strains: A/H1N1, A/H3N2, B/Victoria, and B/Yamagata. GMR was defined as the fold-rise of the geometric mean HI titer from pre- to post-vaccination	At Day 21 post vaccination.

Collaborators and Investigators

• Sponsor: SK Chemicals Co., Ltd.
• Investigators: Principal Investigator: Won Suk Choi, MD, PhD, Korea University; Principal Investigator: Seong-Heon Wie, MD, PhD, Catholic University St. Vincent's Hospital; Principal Investigator: Jacob Lee, MD, PhD, Hallym University Kangnam Sacred Heart Hospital; Principal Investigator: Shin Woo Kim, MD, PhD, Kyungpook University Hospital; Principal Investigator: Hye Won Jeong, MD, Chungbuk university hospital; Principal Investigator: Sook-In Jung, MD, Chonnam University Hospital; Principal Investigator: Yeon-Sook Kim, MD, PhD, Chungnam University Hospital; Principal Investigator: Heung Jeong Woo, MD, PhD, Hallym University Dongtan Sacred Heart Hospital

Publications and helpful links

General Publications

• Choi WS, Noh JY, Song JY, Cheong HJ, Wie SH, Lee JS, Lee J, Kim SW, Jeong HW, Jung SI, Kim YS, Woo HJ, Kim KH, Kim H, Kim WJ. Immunogenicity and safety of a cell culture-derived inactivated quadrivalent influenza vaccine (NBP607-QIV): A randomized, double-blind, multi-center, phase III clinical trial in adults and elderly subjects. Hum Vaccin Immunother. 2017 Jul 3;13(7):1653-1660. doi: 10.1080/21645515.2017.1297351. Epub 2017 Apr 13.

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (ACTUAL): December 1, 2014
• Study Completion (ACTUAL): May 1, 2015

Study Registration Dates

• First Submitted: June 3, 2015
• First Submitted That Met QC Criteria: June 5, 2015
• First Posted (ESTIMATE): June 10, 2015

Study Record Updates

• Last Update Posted (ACTUAL): May 8, 2020
• Last Update Submitted That Met QC Criteria: April 27, 2020
• Last Verified: June 1, 2015

More Information

Terms related to this study

• Keywords: Influenza vaccine; Quadrivalent; Inactivated cell culture-derived
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: NBP607-QIV_FluA_III_2014