Safety and Immunogenicity of GPO Seasonal Tetravalent Inactivated Split Virion Influenza Vaccine in Healthy Thais

Study Overview
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Brief Summary
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The study is aim to evaluate the safety and immunogenicity of one dose TetraFluvac TF vaccine (15 μg HA per strain per dose) of the GPO seasonal quadrivalent inactivated split virion influenza vaccine in healthy adults aged 18 years and above over 90 days post-injection.

Detailed Description
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This is a double blind randomized study consisting of two phases - Phase I and Phase II. Phase I of the study A total of 40 healthy participants aged 18 years and above will be enrolled (1:1 ratio, 20 TetraFluvac TF vaccine and 20 Vaxigrip vaccine (Commercially available seasonal quadrivalent split, manufactured by Sanofi Pasteur, Ltd. France) Phase II of the study A total of 250 healthy participants will be enrolled (4:1 ratio, 200 TetraFluvac TF vaccine and 50 Vaxigrip vaccine (Commercially available seasonal quadrivalent split , manufactured by Sanofi Pasteur, Ltd. France) One dose of the TetraFluvac TF or Commercially available seasonal quadrivalent split vaccine for Southern Hemisphere in 2023 will be given 0.5 ml by intramuscular route. Total follow-up is 90 days. The vaccine will be administered via the intramuscular route; the preferred injection site will be the deltoid of the non-dominant arm. After vaccination participants will remain at the clinic for at least 30 minutes to observe for any reactogenicity after immunization. Blood specimens for immune response will be collected on Day 0 prior to vaccination, Day 28, Day 60, and day 90. Blood specimen for safety will be collected Day 28 for participants Phase I only for clinical hematology and chemistry. A DSMB, composed of at least three independent members with expertise in vaccine clinical trials, will be convened to provide additional safety oversight. In Phase I, the DSMB will meet to review all safety profiles of 28 days after immunization. After completing Day 7 of phase I with no safety concern, the screening for phase II can be started. However, the vaccination of phase II will occur after the recommendation of the DSMB.There should be no safety concerns from DSMB meeting for continue Phase II. In Phase II, the DSMB will meet to review all safety profiles after vaccination of 100 participants for completion of Phase II.

Official Title
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A Phase I/II Randomized Double Blind Controlled Study to Evaluate the Safety and Immunogenicity of GPO Seasonal Tetravalent Inactivated Split Virion Influenza Vaccine in Healthy Thais

Conditions
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Influenza

Intervention / Treatment
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* Biological: TetraFluvac TF vaccine
* Biological: Vaxigrip vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18 years and above Having Thai ID card or equivalent Able to read and provide written informed consent prior to performance of any study-specific procedure Healthy as defined by no clinically significant acute medical condition, and no chronic medical condition that has not been controlled within 90 days of randomization, as determined by medical history, physical examination, screening laboratory test results, and clinical assessment of the investigator. All hematology, biochemistry and urine analysis are within normal range or of no clinical significance (not higher than 1.5 time of normal value without any clinical finding from history and physical examination) Exclusion Criteria: Known history of egg allergy Having had recently influenza infection confirmed as H1N1, H3N2, or Flu B within 3 months preceding enrollment to the trial Vaccination against influenza in the past 6 months preceding enrollment to the trial History of bronchial asthma, chronic lung diseases, chronic rhinitis History of immunodeficiency state History of immunosuppression < 6 months prior to immunization History of anaphylactic or other allergic reactions to influenza vaccine or any vaccine component or excipient (e.g. gentamicin or thimerosal) Acute infectious with fever > 38 degree Celsius and noninfectious diseases (within 72 hours) preceding enrollment in the trial The participants who have been taking immunoglobulin products or have had a blood transfusion during past 3 months before the beginning of the experiment Participation in other research study Pregnancy or plan to become pregnant for 60 days after enrollment or breast feeding Current alcohol abuse or drug addiction that might interfere with the ability to comply with trial procedures Any condition that in the opinion of the investigator would pose a health risk to the subject if enrolled, or could interfere with the evaluation of the vaccine Employee of any person employed by the Sponsor, the contract research organization (CRO), the PI, study site personnel, or site. Any test for HIV, HBsAg, Hep C antibody shows positive results with clinically significance

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Double (Participant, Investigator)
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TetraFluvac TF vaccine<br>20 participants in phase I study and 200 participants in phase II study will receive a prefilled single dose of 0.5 ml of TetraFluvac TF vaccine will be administered via the intramuscular route; the preferred injection site will be the deltoid of the non-dominant arm. | Biological: TetraFluvac TF vaccine<br>* The vaccine is a seasonal quadrivalent inactivated split virion influenza vaccine [A/Sydney/5/2021(H1N1) pdm09-like virus and A/Darwin/9/2021 (H3N2)-like virus and B/Austria/1359417/2021 (B/Victoria Lineage)-like virus and B/Phuket/3073/2013 (B/Yamagata lineage)-like virus] produced by The Government Pharmaceutical Organization (GPO), Thailand. Each prefilled dose of TetraFluvac TF contains a total of 60 micrograms (μg) hemagglutinin (HA) per 0.5 ml dose (15 μg HA per strain per dose), to be administered by intramuscular (IM) injection.<br>|
| Active Comparator: Vaxigrip vaccine<br>20 participants in phase I study and 50 participants in phase II study will receive a prefilled single dose of 0.5 ml Vaxigrip vaccine (Commercially available seasonal quadrivalent split, manufactured by Sanofi Pasteur, Ltd. France) will be administered via the intramuscular route; the preferred injection site will be the deltoid of the non-dominant arm. | Biological: Vaxigrip vaccine<br>* Vaxigrip vaccine is commercially available seasonal quadrivalent inactivated split virion influenza vaccine [A/Sydney/5/2021(H1N1) pdm09-like strain and A/Darwin/9/2021 (H3N2)-like strain and B/Austria/1359417/2021-like strain and B/Phuket/3073/2013-like strain, manufactured by Sanofi Pasteur, Ltd. France. Each prefilled dose of Vaxigrip vaccine contains a total of 60 micrograms (μg) hemagglutinin (HA) per 0.5 ml dose (15 μg HA per strain per dose), to be administered by intramuscular (IM) injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number and percentage of Solicited local adverse events post-vaccination. | Frequency of solicited reportable local adverse events (pain or tenderness, limitation arm movement, erythema, swelling or induration) | 30-minutes after vaccination | 
| Number and percentage of Solicited local adverse events post-vaccination. | Frequency of solicited reportable local adverse events (pain or tenderness, limitation arm movement, erythema, swelling or induration) | day 1 | 
| Number and percentage of Solicited local adverse events post-vaccination. | Frequency of solicited reportable local adverse events (pain or tenderness, limitation arm movement, erythema, swelling or induration) | day 2 | 
| Number and percentage of Solicited local adverse events post-vaccination. | Frequency of solicited reportable local adverse events (pain or tenderness, limitation arm movement, erythema, swelling or induration) | day 3 | 
| Number and percentage of Solicited local adverse events post-vaccination. | Frequency of solicited reportable local adverse events (pain or tenderness, limitation arm movement, erythema, swelling or induration) | day 4 | 
| Number and percentage of Solicited local adverse events post-vaccination. | Frequency of solicited reportable local adverse events (pain or tenderness, limitation arm movement, erythema, swelling or induration) | day 5 | 
| Number and percentage of Solicited local adverse events post-vaccination. | Frequency of solicited reportable local adverse events (pain or tenderness, limitation arm movement, erythema, swelling or induration) | day 6 | 
| Number and percentage of Solicited local adverse events post-vaccination. | Frequency of solicited reportable local adverse events (pain or tenderness, limitation arm movement, erythema, swelling or induration) | day 7 | 
| Number and percentage of Solicited systemic adverse events post-vaccination. | Frequency of solicited reportable systemic adverse events (fever, chill, headache, rhinorrhea, fatigue or malaise, myalgia, arthralgia, rash, nausea or vomiting, diarrhea) | 30-minutes after vaccination | 
| Number and percentage of Solicited systemic adverse events post-vaccination. | Frequency of solicited reportable systemic adverse events (fever, chill, headache, rhinorrhea, fatigue or malaise, myalgia, arthralgia, rash, nausea or vomiting, diarrhea) | day 1 | 
| Number and percentage of Solicited systemic adverse events post-vaccination. | Frequency of solicited reportable systemic adverse events (fever, chill, headache, rhinorrhea, fatigue or malaise, myalgia, arthralgia, rash, nausea or vomiting, diarrhea) | day 2 | 
| Number and percentage of Solicited systemic adverse events post-vaccination. | Frequency of solicited reportable systemic adverse events (fever, chill, headache, rhinorrhea, fatigue or malaise, myalgia, arthralgia, rash, nausea or vomiting, diarrhea) | day 3 | 
| Number and percentage of Solicited systemic adverse events post-vaccination. | Frequency of solicited reportable systemic adverse events (fever, chill, headache, rhinorrhea, fatigue or malaise, myalgia, arthralgia, rash, nausea or vomiting, diarrhea) | day 4 | 
| Number and percentage of Solicited systemic adverse events post-vaccination. | Frequency of solicited reportable systemic adverse events (fever, chill, headache, rhinorrhea, fatigue or malaise, myalgia, arthralgia, rash, nausea or vomiting, diarrhea) | day 5 | 
| Number and percentage of Solicited systemic adverse events post-vaccination. | Frequency of solicited reportable systemic adverse events (fever, chill, headache, rhinorrhea, fatigue or malaise, myalgia, arthralgia, rash, nausea or vomiting, diarrhea) | day 6 | 
| Number and percentage of Solicited systemic adverse events post-vaccination. | Frequency of solicited reportable systemic adverse events (fever, chill, headache, rhinorrhea, fatigue or malaise, myalgia, arthralgia, rash, nausea or vomiting, diarrhea) | day 7 | 
| Number and percentage of participants with unsolicited adverse events | All unsolicited adverse events during 90 days will be analysed in terms of number and percentage and relationship to study vaccine Number and percentage of participants with unsolicited adverse events | day 0 up to day 90 | 
| Number and percentage of participants with AESI | Number and percentage of participants with AESI | day 0 up to day 90 | 
| Number and percentage of participants with Medically-Attended Adverse Event | Number and percentage of participants with Medically-Attended Adverse Event | day 0 up to day 90 | 
| Number and percentage of participants with Serious Adverse Event | Number and percentage of participants with Serious Adverse Event | day 0 up to day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antihemagglutinin antibody titer changed from baseline. | Seroconversion is defined as a 4-fold rise in HI titer in post-immunization serum relative to pre-immunization serum, or if pre-immunization serum had an undetectable titer (<1:10), attainment of a post-immunization titer of ≥1:40. | day 28 | 
| Antihemagglutinin antibody titer changed from baseline. | Seroconversion is defined as a 4-fold rise in HI titer in post-immunization serum relative to pre-immunization serum, or if pre-immunization serum had an undetectable titer (<1:10), attainment of a post-immunization titer of ≥1:40. | day 60 | 
| Antihemagglutinin antibody titer changed from baseline. | Seroconversion is defined as a 4-fold rise in HI titer in post-immunization serum relative to pre-immunization serum, or if pre-immunization serum had an undetectable titer (<1:10), attainment of a post-immunization titer of ≥1:40. | day 90 | 
| Geometric mean of immune response changed from baseline | The analysis was performed only as intention-to-treat (ITT). The antibody titer values were transformed into log10 titers for calculation of the GMT at every time of assessment | day 28 | 
| Geometric mean of immune response changed from baseline | The analysis was performed only as intention-to-treat (ITT). The antibody titer values were transformed into log10 titers for calculation of the GMT at every time of assessment | day 60 | 
| Geometric mean of immune response changed from baseline | The analysis was performed only as intention-to-treat (ITT). The antibody titer values were transformed into log10 titers for calculation of the GMT at every time of assessment | day 90 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, GPO TetraFluvac Vaccine, TetraFluvac Vaccine, Thais, Thailand, Vaxigrip vaccine, Influenza vaccine