Dose-finding Study of Four Dosage Levels of an H7N9 Influenza Vaccine in Adults Between Ages of 18 Years and 65 Years

Study Overview
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Brief Summary
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Evaluate the safety and immunogenicity of four different doses of H7N9 vaccination in adults between the ages of 18 years and 65 years.

Official Title
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Phase I Multi-center, Observer-Blind, Randomized Dose-Ranging Study of Adjuvanted and Non-Adjuvanted Cell Culture-Derived, Inactivated A/H7N9 Monovalent Subunit Influenza Virus Vaccine (H7N9c) in Adults 18 to <65 Years

Conditions
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H7N9 Influenza

Intervention / Treatment
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* Biological: H7N9c low dose with adjuvant
* Biological: H7N9c medium dose with adjuvant
* Biological: H7N9c high dose with adjuvant
* Biological: H7N9c high dose without adjuvant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult subject ages 18-64 years. Individuals willing to provide written informed consent Individuals in good health. Individuals who can comply with study procedures and follow-up. Exclusion Criteria: Individuals with history of cognitive or behavioral impairment or psychiatric disease, Individuals unable to understand and follow study procedures, History of significant illness, History of chronic medical condition or progressive disease, Allergy to any vaccine component or adverse event related to a vaccine component, Impairment/alteration of the immune system, Presence of progressive or severe neurological disorder, Pregnant or breast-feeding, Female of Child-bearing potential unwilling to use acceptable method of birth control, Presence of medically significant cancer, Receipt of investigational product within 30 day prior to entry into the study, History of previous or suspected illness from avian flu caused by H7N9 virus, History of H7 vaccination, Body temperature of greater than or equal to 38.0°C (100.4◦F) and/or acute illness within 3 days of intended study vaccination, Receipt of any flu vaccination 2 weeks before study entry or 4 weeks after study vaccination, Receipt of any vaccination 2 weeks before study entry or 4 weeks after study vaccination, History of drug or alcohol abuse within the past 2 years, Body Mass Index (BMI) greater than or equal to 35kg/m2, Individuals conducting the study or their immediate family members.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group A<br>H7N9c low dose with adjuvant | Biological: H7N9c low dose with adjuvant<br> <br> |
| Experimental: Group B<br>H7N9c medium dose with adjuvant | Biological: H7N9c medium dose with adjuvant<br> <br> |
| Experimental: Group C<br>H7N9c high dose with adjuvant | Biological: H7N9c high dose with adjuvant<br> <br> |
| Experimental: Group D<br>H7N9c high dose without adjuvant | Biological: H7N9c high dose without adjuvant<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages Of Subjects Achieving Seroconversion After Each Vaccination Of A Cell-Culture Derived H7N9c Vaccine (Day 43) | Percentage of subjects achieving HI seroconversion in HI titer was measured three weeks after second (day 43) vaccination. Seroconversion is defined as postvaccination HI titer> 40 for subjects with baseline (day 1); HI titer <1:10 or a minimum 4-fold increase in titer for subjects with baseline titer >1:10. | Day 43 | 
| Percentages Of Subjects With an HI Titers ≥1:40 After Each Vaccination Of A Cell-Culture Derived H7N9c Vaccine (Day 43) | Percentage of subjects who achieved HI titers≥1:40 was measured at baseline (day 1) and three weeks after second (Day 43) vaccination. | Day 1 and 43 | 
| Number of Subjects Reporting Unsolicited Adverse Events After Receiving Adjuvanted and Unadjuvanted Formulations of H7N9c Vaccine | Safety was assessed as the number of subjects who reported any AEs, and at least possibly related AEs are collected from day 1 to day 43 following vaccination with adjuvanted and unadjuvanted formulations of H7N9c vaccine. | Day 1 to Day 43 | 
| Number of Subjects Reporting Unsolicited Serious Adverse Events After Receiving Adjuvanted and Unadjuvanted Formulations of H7N9c Vaccine | The number of subjects reporting unsolicited adverse events after receiving adjuvanted and unadjuvanted formulations of H7N9c vaccine was reported. Safety was assessed as the number of subjects who reported SAEs, at least possibly related SAEs, new onset of chronic diseases (NOCDs), medically attended AEs, AEs of Special Interest (AESIs), AEs leading to withdrawal from the study were collected from day 1 to day 366 following vaccination with adjuvanted and unadjuvanted formulations of H7N9 vaccine. | Day 1 to Day 366. | 
| Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving Adjuvanted and Unadjuvanted Formulations of H7N9c Vaccine | Safety was assessed as the number of subjects who reported solicited local and systemic adverse events from day 1 to day 7 of vaccination of adjuvanted and unadjuvanted formulations of H7N9c vaccine. | Day 1 through Day 7 after each vaccination. | 
| Geometric Mean Titers Of Subjects After Each Vaccination Of a Cell-Culture Derived H7N9c Monovalent Vaccine, Hemagglutination Inhibition Assay (Day 43) | Immunogenicity was measured by Hemagglutination Inhibition (HI) assay and summarized through the geometric mean titers (GMTs) at baseline (day 1) and three weeks after the second (day 43) vaccination | Day 1 and 43 | 
| Geometric Mean Ratios In Subjects After Each Vaccination Of A Cell-Culture Derived H7N9c Vaccine, HI Assay (Day 43) | Geometric mean ratio (GMR) of subjects was calculated as the ratio of postvaccination to prevaccination HI GMTs three weeks after second (day 43) vaccination. | Day 43 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titers Of Subjects After Each Vaccination Of A Cell-Culture Derived H7N9c Monovalent Vaccine, HI Assay (Day 22) | Immunogenicity was measured by HI assay and summarized through the GMTs at baseline (day 1) and three weeks after the first (day 22) vaccination. | Day 1 and 22 | 
| Geometric Mean Ratios In Subjects After Each Vaccination Of A Cell-Culture Derived H7N9c Vaccine, HI Assay (Day 22) | GMR of subjects was calculated as the ratio of postvaccination to prevaccination HI GMTs three weeks after first (day 22) vaccination. | Day 22 | 
| Percentages Of Subjects Achieving Seroconversion After Each Vaccination Of A Cell-Culture Derived H7N9c Vaccine (Day 22) | Percentage of subjects achieving HI seroconversion in HI titer was measured three weeks after first (day 22) vaccination. Seroconversion is defined as postvaccination HI titer> 40 for subjects with baseline (day 1); HI titer <1:10 or a minimum 4-fold increase in titer for subjects with baseline titer >1:10. | Day 22 | 
| Percentages Of Subjects With an HI Titers≥1:40 After Each Vaccination Of A Cell-Culture Derived H7N9c Vaccine (Day 22) | Percentage of subjects who achieved HI titers≥1:40 was measured at baseline (day 1) and three weeks after first (Day 22) vaccination. | Day 1 and 22. | 
| Geometric Mean Titers at Six Months and One Year After Vaccination Of A Cell-Culture Derived H7N9c Vaccine, HI Assay (Persistence) | The immunogenicity was measured as GMTs in subjects as persistence at six months (day 183) and one year (day 366) after the first vaccination as measured by Hemagglutination Inhibition (HI) Assay. | Day 183 and 366. | 
| Geometric Mean Ratios at Six Months and One Year After the First Vaccination Of A Cell-Culture Derived H7N9c Vaccine, HI Assay (Persistence) | GMR of subjects was calculated as the ratio of postvaccination to prevaccination HI GMTs six months (day 183) and one year (day 366) after the first vaccination. | Day 183 and 366 | 
| Percentages Of Subjects Achieving Seroconversion at Six Months and One Year After Vaccination Of A Cell-Culture Derived H7N9c Vaccine (Persistence) | Percentage of subjects with HI seroconversion was measured as HI titer persistence at six months (day 183) and one year (day 366) after the first vaccination. Seroconversion is defined as postvaccination HI titer>40 for subjects with baseline (day 1); HI titer <1:10 or a minimum four-fold increase in titer for subjects with baseline titer>1:10. | Day 183 and 366 | 
| Percentages Of Subjects With an HI Titers ≥1:40 at Six Months and at One Year After the First Vaccination Of A Cell-Culture Derived H7N9c Vaccine (Persistence) | Percentages of subjects who achieved HI titers≥1:40 was measured at six months (day 183) and one year (day 366) after the first vaccination of a cell-culture derived H7N9 vaccine. | Day 183 and 366 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, H7N9, Vaccine