A Phase I/IIa Study of GC3110A (Quadrivalent Influenza Vaccine)

Study Overview
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Brief Summary
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The purpose of this study is to determine whether GC3110A (a QIV) is effective compared to GC Flu Pre-filled Syringe Inj. (a marketed TIV) after single intramuscular administration in Korean healthy adults. The comparator, GC Flu pre-filled syringe inj. is a trivalent influenza vaccine (TIV) including viruses representing 3 influenza strains (one A/HIN1, one A/H3N2, and one B). However, two antigenically distinct lineages of influenza B (Victoria and Yamagata) co-circulate annually in the United States. Predicting which lineage of influenza B will predominate during a season is challenging, and cross-protection by immunization against the other lineage is expected to be low. One proposed alternative is to produce a quadrivalent influenza vaccine (QIV) including an influenza B virus from each of the two circulating lineages. GC3110A is a new quadrivalent influenza vaccine (QIV), which contains all of 4 vaccine components WHO recommends for use in the 2013-14 influenza season (northern hemisphere winter) and includes two influenza B viruses. GC3110A is expected to show the additional public health benefit compared with traditional TIV.

Detailed Description
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This study is the first in human trial of GC3110A and is designed as an adaptive Phase I/IIa to ensure participants protection. Part A is an open-label and single arm study in 9 healthy volunteers. Data and Safety Monitoring Board (DSMB) will review the solicited/unsolicited adverse events conditionally if any toxicity of Grade 3 or 4 has been reported during 7 days after vaccination. Part B is a randomized (2:1), double-blind, active controlled study and a total of 75 volunteers will participate in this part. Adverse events assessment will be done according to the 'Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials'.

Official Title
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A Randomized, Open-label (Part A) or Double-blind (Part B), Active-controlled (Part B) Phase I/IIa Study to Investigate the Safety, Tolerability, and Immunogenicity of GC3110A (Quadrivalent Influenza Vaccine)

Conditions
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Influenza

Intervention / Treatment
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* Biological: Quadrivalent influenza vaccine
* Biological: Trivalent influenza vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Given written informed consent Healthy Korean adults (age: between over 19 and under 65) Korean adults who agree with 21 days follow up after vaccination and good compliance to study procedures Those who are able to comply with the requirements for the study Exclusion Criteria: Inability in written/verbal communication Subjects who have participated in other interventional study within 30 days Alcohol or drug abuse within 6 months Heavy drinkers or subjects who do not agree to stop drinking for 3 days before vaccination and other 3 days after vaccination Who got the treatment of psychotropic drugs and narcotic analgesic drugs within 6 months of enrollment Hypersensitivity with drug or active ingredient Disorders in immune function History of Guillain-Barré syndrome Disease/medications which are likely to cause any severe bleeding Active infection or experience of fever (>38.0 ℃) within 72 hours following vaccination Oral temperature >38.0 ℃ at the vaccination day Erythema, tattoo, injury at shoulder (vaccination site) Hypersensitivity with egg, chicken, or any of the vaccine components, or Neomycin, Gentamicin Influenza vaccination within 6months Any vaccination within 30 days Concomitant medications/therapy such as immunosuppressants or immune modifying drugs, systemic corticosteroids, immunoglobulins, blood or blood- derived products, or anti-cancer chemotherapy or radiation therapy within3 months Pregnant or breast-feeding women Clinically significant underlying diseases or medical history at investigator's discretion

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 65 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: Quadrivalent influenza vaccine(Part A)<br>Day 1: GC3110A, 0.5ml, intramuscular, a single dosing | Biological: Quadrivalent influenza vaccine<br>* GC3110A, 0.5ml, intramuscular, a single dosing at Day 1<br>* Other names: GC3110A;|
| Experimental: Quadrivalent influenza vaccine(Part B)<br>Day 1: GC3110A, 0.5ml, intramuscular, a single dosing | Biological: Quadrivalent influenza vaccine<br>* GC3110A, 0.5ml, intramuscular, a single dosing at Day 1<br>* Other names: GC3110A;|
| Active Comparator: Trivalent influenza vaccine(Part B)<br>Day 1: GC Flu Pre-filled Syringe Inj., 0.5ml, intramuscular, a single dosing | Biological: Trivalent influenza vaccine<br>* GC Flu Pre-filled Syringe Inj., 0.5ml, intramuscular, a single dosing at Day 1<br>* Other names: GC Flu Pre-filled Syringe Inj.;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Solicited adverse events following vaccination | Solicited injection site reactions: Pain, Tenderness, Erythema, Redness, Induration, and Swelling; Solicited systemic reactions: Fever, Sweating, Chill, Nausea, Vomiting, Diarrhea, Headache, Fatigue, Myalgia, arthralgia. | Day 1 up to 7 Days post vaccination | 
| Unsolicited adverse events following vaccination | It can be estimated by Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials | Day 1 up to 22 Days post vaccination | 
| Seroconversion rate of HI (Hemagglutination Inhibition) antibody for each strain |  | Day 22 post vaccination | 
| Seroprotection rate of HI (Hemagglutination Inhibition) antibody for each strain |  | Day 22 post vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Abnormalities in physical examination, vital signs, and/or clinical laboratory tests |  | Day 22 post vaccination | 
| GMT(geometric mean titers) for each strain |  | Day 22 post vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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QIV, Quadrivalent Influenza Vaccine, Influenza vaccine, Vaccination