Safety, Tolerability and Immunogenicity of Fluzone® With and Without JVRS-100 in Elderly Subjects

Study Overview
=================
Brief Summary
-----------------
This study is designed to determine the optimal dose of JVRS-100 and assess safety, tolerability and immunogenicity of Fluzone® vaccine administered with JVRS-100 adjuvant at one of three dose levels compared to Fluzone® vaccine administered alone, in 472 adults aged ≥65 years.

Detailed Description
-----------------
Approximately 472 subjects will be enrolled in this study. The study population will include elderly male and female subjects aged ≥65 years who are living in the community (including assisted living environments) and who are very fit to moderately frail. One hundred subjects (approximately 25 in each treatment arms) will be vaccinated, and 14 days will elapse during which safety parameters are monitored by a Data and Safety Monitoring Board (DSMB), before randomizing the remaining 372 subjects.

Official Title
-----------------
Randomized, Double Blind, Controlled Phase II Trial of the Safety, Tolerability and Immunogenicity of Fluzone® Inactivated Trivalent Influenza Virus Vaccine Administered With and Without JVRS-100 Adjuvant in Subjects 65 Years and Older

Conditions
-----------------
Influenza

Intervention / Treatment
-----------------
* Biological: Fluzone® vaccine with JVRS-100 adjuvant or Fluzone alone


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Be adult volunteers aged ≥65 years Live in the community, independently or in an assisted living environment Be Class 1-5, as defined by the CSHA-CFS If female, will be post-menopausal Will be available for the duration of the trial (21-day On Study Period) and Follow-Up (4 and 9 months after vaccination) Be 'probably not demented' on the Mini-Cog test Provide informed consent Agree to defer receipt of vaccination of novel H1N1 (swine) influenza until after completion of the Day 28 study procedures Exclusion Criteria: Known allergy to eggs or other components of the vaccine. History of severe reaction of any kind to conventional influenza vaccines Be Class 6-7 in the CSHA-CFS or be institutionalized (e.g., in a nursing home) Requiring nursing home-level equivalent care at home or within a community assisted living environment Chronic administration of immunosuppressants or other immune-modifying drugs within 6 months prior to the administration of the study vaccine. Significant cardiovascular disease (e.g., NYHA class 3 through 4 congestive heart failure; myocardial infarction within the past 6 months; unstable angina; coronary angioplasty within the past 6 months; uncontrolled ventricular cardiac arrhythmias); resting heart rate >100; A history of chronic obstructive pulmonary disease or history of other lung disease requiring chronic steroid treatment in excess of a bioequivalent dose of 10 mg prednisone daily; a combined history of lung disease and anemia. Evidence of significant (more than 10 pounds) of unintentional weight loss in the last year. Changed residence or become hospitalized in the last 6 months. Combined history of depression and anemia. Administration of immunoglobulins and/or any blood products within the 3 months preceding the administration of the study vaccine or during the study. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination. Use of any investigational product within 60 days preceding the administration of the study vaccine, or planned use during the study period. Seropositive to HIV or HCV or positive for HBsAg Body temperature >38.1°C (100.6°F) or acute illness within 3 days prior to vaccination (subject may be rescheduled) History of excessive alcohol consumption, drug abuse, or significant psychiatric illness. Be 'probably demented' on the Min-Cog test Need for guardian assistance in completing informed consent Has received vaccination for novel H1N1 (swine) influenza

Ages Eligible for Study
-----------------
Minimum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluzone® vaccine with JVRS-100 (3.75ug)<br>One vaccination on Day 0 with Fluzone® vaccine at 45 ug mixed with JVRS-100 adjuvant at 3.75ug given by IM injection to the upper deltoid. | Biological: Fluzone® vaccine with JVRS-100 adjuvant or Fluzone alone<br>* One vaccination on Day 0 of Fluzone® vaccine at 45ug mixed with one of three doses (3.75ug, 7.5ug, 25ug) of JVRS-100 adjuvant versus Fluzone® vaccine at 45ug alone.<br>|
| Experimental: Fluzone® vaccine with JVRS-100 (7.5ug)<br>One vaccination on Day 0 with Fluzone® vaccine at 45 ug mixed with JVRS-100 adjuvant at 7.5ug given by IM injection to the upper deltoid. | Biological: Fluzone® vaccine with JVRS-100 adjuvant or Fluzone alone<br>* One vaccination on Day 0 of Fluzone® vaccine at 45ug mixed with one of three doses (3.75ug, 7.5ug, 25ug) of JVRS-100 adjuvant versus Fluzone® vaccine at 45ug alone.<br>|
| Experimental: Fluzone® vaccine with JVRS-100 (25ug)<br>One vaccination on Day 0 with Fluzone® vaccine at 45 ug mixed with JVRS-100 adjuvant at 25ug given by IM injection to the upper deltoid. | Biological: Fluzone® vaccine with JVRS-100 adjuvant or Fluzone alone<br>* One vaccination on Day 0 of Fluzone® vaccine at 45ug mixed with one of three doses (3.75ug, 7.5ug, 25ug) of JVRS-100 adjuvant versus Fluzone® vaccine at 45ug alone.<br>|
| Experimental: Fluzone® vaccine alone<br>One vaccination on Day 0 with Fluzone vaccine at 45 ug given by IM injection in the upper deltoid. | Biological: Fluzone® vaccine with JVRS-100 adjuvant or Fluzone alone<br>* One vaccination on Day 0 of Fluzone® vaccine at 45ug mixed with one of three doses (3.75ug, 7.5ug, 25ug) of JVRS-100 adjuvant versus Fluzone® vaccine at 45ug alone.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: The primary safety endpoint of this trial will be the evaluation of adverse events incidence rates between treatment groups. |  | Active Study Duration | 
| Immunogenicity: Dose-response analysis of HAI geometric mean titers (GMT) |  | Day 0, 21, 28, Month 4 and 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety: Comparison of AE rates at intervals between treatment groups. |  | Active Study Duration | 
| Immunogenicity: Comparison of Fluzone® with JVRS-100 by examining seroprotection and seroconversion rates to various antigens, duration of HAI antibody titers, and assessment of cross-reactive HAI responses against drifted strains. |  | Day 0, 21, 28 and Month 4 and 9 | 
| T-cell responses will be measured. |  | Day 0, 7, 14 and 28 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Elderly influenza vaccine