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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Influenza

Intervention / Treatment
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* Biological: NBP607-QIV
* Biological: NBP607-Y
* Biological: NBP607-V


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NBP607-QIV<br>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<br>* Quadrivalent Inactivated Cell Culture-derived Influenza Vaccine containing 4 virus strains; A/H1N1, A/H3N2, B/Yamagata, B/Victoria<br>|
| Active Comparator: NBP607-Y<br>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<br>* Trivalent Inactivated Cell Culture-derived Influenza Vaccine containing 3 virus strains; A/H1N1, A/H3N2, B/Yamagata<br>|
| Active Comparator: NBP607-V<br>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<br>* Trivalent Inactivated Cell Culture-derived Influenza Vaccine containing 3 virus strains; A/H1N1, A/H3N2, B/Victoria<br>|

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza vaccine, Quadrivalent, Inactivated cell culture-derived