Phase 2 Study of TAK-850 in Comparison With Influenza Hemagglutinin (HA) Vaccine in Healthy Adult Participants

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the immunogenicity and safety of TAK-850 administered subcutaneously as a single dose versus influenza HA vaccination in an exploratory manner.

Detailed Description
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This study is a phase 2, single dose study of TAK-850 (cell-culture derived TIV) administered subcutaneously in healthy Japanese adults, designed as a randomized, double-blind, parallel-group, comparative study to evaluate the immunogenicity and safety compared to an egg-derived TIV. The drug being tested in this study is called TAK-850. TAK-850 was tested in healthy volunteers. This study looked at immunogenicity and safety of TAK-850 (cell-derived) compared to an egg-derived influenza vaccine. The study enrolled 400 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the two groups-which will remain undisclosed to the patient and study doctor during the study (unless there is an urgent medical need): TAK-850 Influenza HA vaccine All participants received one injection. This single center trial was conducted in Japan. The overall time to participate in this study was 22 days. Participants made multiple visits to the clinic, including a final visit 21 days after the vaccination for a follow-up assessment.

Official Title
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A Randomized Double-Blind Parallel-Group Comparative Phase 2 Study to Evaluate the Immunogenicity and Safety of a Single Subcutaneous Injection of TAK-850 in Comparison With Influenza HA Vaccine in Healthy Adult Subjects

Conditions
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Influenza Infection

Intervention / Treatment
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* Biological: TAK-850
* Biological: Influenza HA vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In the opinion of the investigator or subinvestigator, the participant is capable of understanding and complying with protocol requirements. The participant signs and dates a written, informed consent form prior to the initiation of any study procedures. The participant is a healthy Japanese adult male or female. The participant is aged 20 to 49 years, inclusive, at the time of informed consent. The participant has a body mass index (BMI) between 18.5 and 25.0 kg/m^2, inclusive, at the time of the eligibility evaluation. A female participant of childbearing potential who is sexually active with a nonsterilized male partner agreed to routinely use adequate contraception from signing of the informed consent throughout the duration of the study. Exclusion Criteria: The participant has received any investigational compound within 4 months prior to injection of study vaccine. The participant has been vaccinated with seasonal influenza vaccine within 6 months prior to injection of study vaccine. The participant has a history of influenza infection within 6 months prior to injection of study vaccine. The participant has been vaccinated with TAK-850 before. The participant is a study site employee, an immediate family member of such an employee, or in a dependent relationship with a study site employee who is involved in the conduct of this study (e.g., spouse, parent, child, sibling), or may consent under duress. The participant has uncontrolled, clinically significant manifestations of neurological, cardiovascular, pulmonary, hepatic, renal, metabolic, gastrointestinal, urologic, endocrine, or other disorders, which may impact the ability of the participant to participate or potentially confound the study results. The participant has an oral temperature >= 37.5 °C prior to injection of study vaccine on Day 1. The participant has any medically diagnosed or suspected immune deficient condition. The participant has an immune compromising condition or disease, or is currently undergoing a form of treatment or was undergoing a form of treatment that can be expected to influence immune response within 30 days prior to injection of study vaccine. Such treatments include systemic or high dose inhaled corticosteroids (> 800 µg/day of beclomethasone dipropionate or equivalent; the use of inhaled and nasal steroids that do not exceed this level will be permitted), radiation therapy, and other immunosuppressive and cytotoxic drugs. The participant has received antipyretics within 4 hours prior to the injection of study vaccine. The participant has a history of Guillain-Barré Syndrome, demyelinating disorders (including acute disseminated encephalomyelitis [ADEM] and multiple sclerosis), or convulsions. The participant has a functional or surgical asplenia. The participant has a rash, other dermatologic conditions, or tattoos which may interfere with the evaluation of injection site reaction. The participant has a history of, or is infected with the Hepatitis B Virus (HBsAgs), Hepatitis C Virus (HCV), or Human Immunodeficiency Virus (HIV). The participant has known hypersensitivity to any component of TAK-850 or Influenza HA Vaccine. The participant has a history of severe allergic reactions or anaphylaxis. The participant has a history of drug abuse (defined as any illicit drug use) or a history of alcohol abuse within 1 year prior to injection of study vaccine or is unwilling to agree to abstain from excessive alcohol and drugs throughout the study. The participant has received any blood products (blood transfusion or immunoglobulin) within 90 days prior to injection of study vaccine. The participant has received a live vaccine within 4 weeks (28 days) or an inactivated vaccine within 2 weeks (14 days) prior to injection of study vaccine. If female, the participant is pregnant or lactating or intending to become pregnant before signing of informed consent, during treatment, or within 12 weeks after injection of study vaccine; or intending to donate ova during this time period. The participant has donated whole blood >= 200 mL within 4 weeks (28 days), >= 400 mL within 12 weeks (84 days), >= 800 mL within 52 weeks (364 days) or blood components within 2 weeks (14 days) prior to injection of study vaccine. The participant has abnormal laboratory values that suggest a clinically significant underlying disease at the assessment prior to the injection of study vaccine, or the participant has the following laboratory abnormalities: alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) more than 3 times the respective upper limits of normal. In the opinion of the investigator or subinvestigator, the participant is unlikely to comply with protocol requirements or is considered ineligible for any other reasons.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 49 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAK-850<br>A single dose of 0.5 mL TAK-850 (15 μg of hemagglutinin [HA] antigen per strain) is injected subcutaneously into the upper arm. | Biological: TAK-850<br>* TAK-850 subcutaneous injection<br>|
| Active Comparator: Influenza HA Vaccine<br>A single dose of the 0.5 mL influenza HA vaccine (15 μg of HA antigen per strain) is injected subcutaneously into the upper arm. | Biological: Influenza HA vaccine<br>* Influenza HA vaccine subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion Rate of Hemagglutination Inhibition (HI) Antibody Titer (Egg-Derived Antigen) | Seroconversion rate was measured by hemagglutination inhibition (HI) antibody titer (egg-derived antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after vaccination. Seroconversion rate was defined as the percentage of participants achieving a minimal 4-fold increase from the Baseline HI antibody titer in participants with a Baseline titer ≥10, or achieving an HI antibody titer of ≥40 in participants with a Baseline titer <10. | Baseline and Day 22 | 
| Geometric Mean Titer (GMT) of HI Antibody Titer (Egg-Derived Antigen) | Geometric mean titer (GMT) of HI antibody titer (egg-derived antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after vaccination. Day 1 data is reported for reference. | Days 1 and 22 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroprotection Rate of HI Antibody Titer (Egg-Derived Antigen) | Seroprotection rate, defined as the percentage of participants with HI antibody titer of ≥40, was measured by HI antibody titer (egg-derived antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after vaccination. Day 1 data is reported for reference. | Days 1 and 22 | 
| Geometric Mean Fold Increase in HI Antibody Titer (Egg-Derived Antigen) | Geometric mean fold increase in HI antibody titer (egg-derived antigen) for each of the three strains (A/H1N1 strain, A/H3N2 strain, B strain), 21 days after vaccination, as compared with Baseline. | Baseline and Day 22 | 
| Seroconversion Rate of Single Radial Hemolysis (SRH) Antibody Titer (Egg-Derived Antigen) | Seroconversion rate, defined as the percentage of participants with a Baseline SRH antibody titer of >4 mm^2 achieving a minimal 50% increase, or a Baseline SRH antibody titer of ≤4 mm^2 achieving a SRH antibody titer of ≥25 mm^2, as measured by single radial hemolysis (SRH) antibody titer (egg-derived antigen) for each of the three strains, 21 days after vaccination. | Baseline and Day 22 | 
| GMT of SRH Antibody Titer (Egg-Derived Antigen) | GMT of SRH antibody titer (egg-derived antigen) for each of the three strains, 21 days after vaccination. Day 1 data is reported for reference. | Days 1 and 22 | 
| Seroprotection Rate of SRH Antibody Titer (Egg-Derived Antigen) | Seroprotection rate, defined as the percentage of participants with SRH antibody titer ≥25 mm^2, was measured by SRH antibody titer (egg-derived antigen) for each of the three strains, 21 days after vaccination. Day 1 data is reported for reference. | Days 1 and 22 | 
| Geometric Mean Fold Increase in SRH Antibody Titer (Egg-Derived Antigen) | Geometric mean fold increase in SRH antibody titer (egg-derived antigen) for each of the three strains, 21 days after vaccination, as compared with Baseline. | Baseline and Day 22 | 
| Seroconversion Rate of HI Antibody Titer (Vero-Derived Antigen) | Seroconversion rate, defined as the percentage of participants with a Baseline HI antibody titer of ≥10 achieving a minimal 4-fold increase, or a Baseline HI antibody titer of <10 achieving a HI antibody titer of ≥40, was measured by HI antibody titer (Vero-derived antigen) for each of the three strains, 21 days after vaccination. | Baseline and Day 22 | 
| GMT of HI Antibody Titer (Vero-Derived Antigen) | GMT of HI antibody titer (Vero-derived antigen) for each of the three strains, 21 days after vaccination. Day 1 data is reported for reference. | Days 1 and 22 | 
| Seroprotection Rate of HI Antibody Titer (Vero-Derived Antigen) | Seroprotection rate, defined as the percentage of participants with HI antibody titer ≥40, was measured by HI antibody titer (Vero-derived antigen) for each of the three strains, 21 days after vaccination. Day 1 data is reported for reference. | Days 1 and 22 | 
| Geometric Mean Fold Increase in HI Antibody Titer (Vero-Derived Antigen) | Geometric mean fold increase in HI antibody titer (Vero-derived antigen) for each of the three strains, 21 days after vaccination, as compared with Baseline. | Baseline and Day 22 | 
| Seroconversion Rate of SRH Antibody Titer (Vero-Derived Antigen) | Seroconversion rate, defined as the percentage of participants with a Baseline SRH antibody titer of >4 mm^2 achieving a minimal 50% increase, or a Baseline SRH antibody titer of ≤4 mm^2 achieving a SRH antibody titer of ≥25 mm^2, was measured by SRH antibody titer (Vero-derived antigen) for each of the three strains, 21 days after vaccination. | Baseline and Day 22 | 
| GMT of SRH Antibody Titer (Vero-Derived Antigen) | GMT of SRH antibody titer (Vero-derived antigen) for each of the three strains, 21 days after vaccination. Day 1 data is reported for reference. | Days 1 and 22 | 
| Seroprotection Rate of SRH Antibody Titer (Vero-Derived Antigen) | Seroprotection rate, defined as the percentage of participants with SRH antibody titer ≥25 mm^2, was measured by SRH antibody titer (Vero-derived antigen) for each of the three strains, 21 days after vaccination. Day 1 data is reported for reference. | Days 1 and 22 | 
| Geometric Mean Fold Increase in SRH Antibody Titer (Vero-Derived Antigen) | Geometric mean fold increase in SRH antibody titer (Vero-derived antigen) for each of the three strains, 21 days after vaccination, as compared with Baseline. | Baseline and Day 22 | 
| Percentage of Participants With Solicited Local and Systemic Adverse Events (AEs) | Participants recorded solicited injection site and systemic adverse events in a Subject Diary. Solicited Locals AEs were: Injection Site Pain, Injection Site Redness, Injection Site Swelling, Injection Site Induration and Injection Site Ecchymosis. Solicited Systemic AEs were: Pyrexia, Malaise, Chills, Fatigue, Headache, Sweaty, Myalgia, Arthralgia, Nausea and Vomiting. | 22 Days | 
| Percentage of Participants Reporting One or More Treatment-emergent Adverse Events (TEAE) | Adverse events are defined as unfavorable and unintended signs, symptoms or diseases temporally associated with the use of a medicinal product, regardless of relationship to the medicinal product. TEAE is defined as an adverse event with an onset that occurs after receiving study drug. | 22 days | 
| Percentage of Participants With Abnormal Safety Laboratory Tests at Least Once Post Dose Reported as AEs | The percentage of participants with any abnormal standard safety laboratory values (Chemistry, Hematology and Urinalysis) collected throughout the study reported as AEs. | 22 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine