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

Phase 3

Completed

• Conditions: Influenza
• Interventions: Biological: NBP607-V; Biological: NBP607-QIV; Biological: NBP607-Y

• Registration Number: NCT02467842
• Lead Sponsor: SK Chemicals Co., Ltd.

Brief Summary

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.

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 Timeline

• Study Start: 2014-10
• Primary Completion: 2014-12
• Study Completion: 2015-05
• Status Verified: 2015-06
• Study First Submitted: 2015-06-03
• Study First Submitted QC: 2015-06-05
• Study First Posted: 2015-06-10
• Results First Submitted: 2018-12-06
• Results First Submitted QC: 2020-04-27
• Last Update Submitted: 2020-04-27
• Results First Posted: 2020-05-08
• Last Update Posted: 2020-05-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1503

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NBP607-V	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
NBP607-QIV	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
NBP607-Y	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

Primary Outcome Measures

Name	Time	Method
Seroprotection Rate (SPR) of NBP607-QIV in the Elderly Subject Aged ≥60 Years	At Day 21 post vaccination.	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.
Geometric Mean Ratio (GMR) of NBP607-QIV in the Elderly Subject Aged ≥60 Years	At Day 21 post vaccination.	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.
Geometric Mean HI Titers (GMTs) After Vaccination in All Subjects	At Day 21 post vaccination.	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).
Seroconversion Rate (SCR) After Vaccination in All Subjects	At Day 21 post vaccination.	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).
Seroconversion Rate (SCR) of NBP607-QIV in the Elderly Subject Aged ≥60 Years	At Day 21 post vaccination.	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

Secondary Outcome Measures

Name	Time	Method
Geometric Mean HI Titers (GMTs) of Each B Strain After Vaccination in All Subjects	At Day 21 post vaccination.	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).
Seroconversion Rate (SCR) of B Strain After Vaccination in All Subjects	At Day 21 post vaccination.	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
Seroconversion Rate (SCR) of NBP607-QIV in the Adults Aged 19 to 59 Years	At Day 21 post vaccination.	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
Geometric Mean Ratio (GMR) of NBP607-QIV in the Subjects Aged 19 to 59 Years	At Day 21 post vaccination.	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
Seroprotection Rate (SPR) of NBP607-QIV in the Adults Aged 19 to 59 Years	At Day 21 post vaccination.	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.