Phase 1 Study to Assess the Safety of Inactivated Split Influenza Vaccine and Control Vaccine in Korean Volunteer

A Randomized, Active-Comparator, Open-Label, Phase 1 Clinical Trial to Assess the Safety of the 'IL-YANG Inactivated Split Influenza Vaccine' and Fluarix Prefilled Syringe in Healthy Korean Male Volunteer

The purpose of this study to evaluate the safety of IL-YANG Inactivated Split Influenza Vaccine (IL-YANG FLU Vaccine Prefilled Syringe INJ.) in comparison with Fluarix Prefilled Syringe (inactivated split influenza vaccine) after single-dose intramuscular administration.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Biological: IL-YANG FLU Vaccine Prefilled Syringe INJ.; Biological: Fluarix Prefilled Syringe

Detailed Description

This was a randomized, open-label, active-controlled clinical study. After providing voluntary written informed consent, subjects underwent protocol-specific assessments and tests within the 4 weeks prior to administration of the study vaccine, and those who met all of the inclusion/exclusion criteria were randomized sequentially to the test group or the comparator group according to the pre-generated randomization code. To investigate the safety of the study drug with a two-dose regimen in children, the test group received another dose 28 days after the first dose.

The investigator evaluated the safety and immunogenicity for each subject throughout the study. Safety assessments were performed 28 days after the first dose (Visit 4, End-of-Study Visit) for the comparator group receiving a single-dose regimen of Fluarix Prefilled Syringe, and for the test group receiving a two-dose regimen of the test drug, 28 days after the first dose (Visit 4) and 28 days after the second dose (Visit 6, End-of-Study Visit). Subjects were instructed to record any adverse event occurring after vaccination in the Patient Diary Card. For the immunogenicity assessment, an antibody titer test was performed prior to dosing at Visit 2 (baseline) and 28 days (Visit 4) after the first vaccination for both the test group and comparator group.

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy male subjects between 20 and 55 years of age at screening
• Body weight of ≥ 55kg and within ±20% of ideal body weight (ideal body weight = (height cm - 100)*0.9) at screening
• Subjects with no congenital or chronic disease who were considered suitable for the study after screening assessments (investigator's opinion, medical history, physical examination, laboratory test, chest X-ray, and ECG) conducted within 28 days prior to vaccination
• Subjects who were given, and fully understood, the information about the study, made a voluntary decision, and provided written informed consent, to participate in the study and comply with all applicable study requirements

Exclusion Criteria:

• Subjects who have known or suspected infection with HAV, HBV, HCV, HIV or VDRL
• Subjects who have concurrent or a past history of immune deficiency disease
• Subject who had participated in blood donation within 1 week prior to vaccination, or are planning to participate in blood donation from Day 1 until Month 7 post-vaccination
• Subject with a history of Guillain-Barre syndrome
• Subject with hemophilia or thrombocytopenia, or being treated with an anticoagulant, who are at increased risk of serious bleeding during intramuscular injection
• Subjects who have concurrent or a past history of, malignant tumor of internal organ or blood vessels or skin metastasis
• Subjects with known allergy to a drug, food or latex, who had a history of anaphylaxis
• Subjects who had an acute fever with body temperature > 38.0 Cº within 72 hours prior to administration of the study vaccine or symptoms of suspected acute disease within 14 days prior to administration of the study vaccine
• Subjects who received another experimental drug or vaccine within 28 days before administration of the study vaccine or are planning to receive another experimental drug or vaccine during the study.
• Subjects who had previously received immunoglobulin or blood-derived products within the last 3 months prior to administration of the study vaccine, or are expecting to be treated with immunoglobulin or blood-derived products during the study
• Subjects who had received, or are scheduled to receive, systemic immunosuppressive therapy, radiation therapy or high-dose corticosteroid therapy within the last 6 months prior to administration of the study
• Subjects with a history of, or suspected, drug abuse based on subject interview and physical examination.
• Subjects with excessive consumption of caffeine and alcohol and excessive smoking
• Subject with a known allergy to eggs, chicken, or any components of the study vaccine
• Subjects who in the investigator's opinion, may not be suitable for vaccination or who may interfere with the objective assessment of the study outcomes.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: IL-YANG PFS; IL-YANG FLU Vaccine Prefilled Syringe INJ.	Biological: IL-YANG FLU Vaccine Prefilled Syringe INJ.; Second vaccination (only for the test group) of IL-YANG FLU Vaccine Prefilled Syringe INJ.0.5mL
Active Comparator: TIV PFS; Fluarix Prefilled Syringe	Biological: Fluarix Prefilled Syringe; Fluarix Prefilled Syringe 0.5mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of subjects achieving seroconversion and seroprotection for HI antibody after administration of the study vaccine	Seroconversion: a pre-vaccination (Day 0) hemagglutination-inhibition (HI) antibody titer < 1:10 and a post-vaccination (Day 28) HI antibody titer ≥ 1: 40 (Case 1), or a pre-vaccination (Day 0) HI antibody titer ≥ 1:10 and a minimum four-fold rise in post-vaccination (Day 28) HI antibody titer (Case 2). Seroprotection: post-vaccination (Day 28) HI antibody titer ≥ 1:40	up to Day28(+7)
Solicited local & general Adverse Event, Unsolicited Adverse Event	Solicited local reaction: pain, tenderness, redness, swelling, Solicited general reactions: fever, nausea/vomiting, diarrhea, headache, fatigue, myalgia	up to Day28(+7)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vital signs		up to Day28(+7)
Physical examination		up to Day28(+7)
ECG result		up to Day28(+7)
Clinical laboratory results		up to Day28(+7)
GMT of HI antibody titer before vaccination and after vaccination	Geometric Mean Titer (GMT), as measured by pre-vaccination (Day 0) HI antibody titer and post-vaccination (vaccination + 28 days) HI antibody titer.	up to Day28(+7)
GMR of HI antibody titer before vaccination and after vaccination	Geometric Mean Ratio (GMR), as measured by pre-vaccination (Day 0) HI antibody titer and post-vaccination (vaccination + 28 days) HI antibody titer	up to Day28(+7)
Percentage of subjects with a pre-vaccination (Day 0) HI antibody titer < 1:40, and a minimum four-fold rise in post-vaccination (Day 28) HI antibody titer		up to Day28(+7)

Collaborators and Investigators

• Sponsor: Il-Yang Pharm. Co., Ltd.
• Investigators: Principal Investigator: Min Soo Park, M.D,PhD, Severance Hospital, Yonsei University Health System

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: December 29, 2014
• First Submitted That Met QC Criteria: December 30, 2014
• First Posted (Estimate): January 1, 2015

Study Record Updates

• Last Update Posted (Estimate): January 1, 2015
• Last Update Submitted That Met QC Criteria: December 30, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Influenza; Influenza vaccine; Split influenza vaccine; Seasonal influenza vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: IY_IFEZ_102