Safety Study of Recombinant M2e Influenza-A Vaccine in Healthy Adults

Study Overview
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Brief Summary
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This multi-center study will be conducted in the United States with up to 80 healthy adult subjects. Subjects will be scheduled to receive a total of two (2) injections with 1 injection each administered. Subjects will be randomized according to a randomization scheme.

Detailed Description
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All subjects will be followed up for 60 days post-randomization and through the influenza season. Following the influenza season, a subset of the subjects will receive a booster vaccine at the 12 month time point. The subjects will further be assessed at 2 days, 7 days, 15 days, 30 days and 6 months following the booster vaccination.

Official Title
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A Phase 1, Randomized, Placebo-Controlled, Double-Blind, Safety, Reactogenicity, and Immunogenicity of Recombinant M2e Influenza-A Vaccine Candidate ACAM FLU-A) in Healthy Adults

Conditions
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Influenza

Intervention / Treatment
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* Biological: Influenza A Vaccine: ACAM FLU-A
* Biological: Influenza A Vaccine: ACAM FLU-A
* Biological: Influenza A Vaccine: ACAM FLU-A
* Biological: Saline placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult males or females 18 - 40 years of age in good general health Exclusion Criteria: Known allergies or severe reactions to any of the vaccine components including those to adjuvants History of severe allergic reactions, including angioedema; History of asthma or recurrent wheezing; (current or within past 2 years); History of neurological symptoms or signs following administration of any vaccine;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Study Group 1<br>ACAM-FLU-A low dose + Adjuvant 1 | Biological: Influenza A Vaccine: ACAM FLU-A<br>* 0.5 mL ACAM-FLU-A low dose + Adjuvant 1, Intramuscular<br>* Other names: ACAM FLU-A;|
| Experimental: Study Group 2<br>ACAM-FLU-A low dose + Adjuvant 2 | Biological: Influenza A Vaccine: ACAM FLU-A<br>* 0.5 mL ACAM-FLU-A low dose + Adjuvant 2, Intramuscular<br>* Other names: ACAM FLU-A;|
| Experimental: Study Group 3<br>ACAM-FLU-A low dose | Biological: Influenza A Vaccine: ACAM FLU-A<br>* 0.5 mL ACAM FLU-A low dose, Intramuscular<br>* Other names: ACAM FLU-A;|
| Placebo Comparator: Study Group 4<br>Saline placebo | Biological: Saline placebo<br>* 0.5 mL, Intramuscular<br>* Other names: USP Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Reporting Adverse Events by System Organ Class After Vaccination With ACAM FLU A, or ACAM FLU A With Adjuvant, or a Placebo Vaccine. |  | Day 0 through Day 60 post-vaccination | 
| Number of Participants Reporting a Solicited Injection Site or Systemic Adverse Event After Vaccination With ACAM FLU A, or ACAM FLU A With Adjuvant, or Placebo Vaccine. | Solicited Injection Site Adverse Events: Erythema, Induration, Pain, Pruritus, Swelling, Rash. Solicited Systemic Adverse Events: Lymph Node Pain, Pyrexia (Temperature), Chills, Constipation, Diarrhoea, Fatigue, Headache, Malaise, Myalgia, Nausea, Vomiting, Alanine Aminotransferase Increased, Aspartate Aminotransferase Increased, Blood Creatinine Increased, Haemoglobin Decreased, Platelet Count Decreased, White Blood Cell Count Increased. | Day 0 through Day 7 post-vaccination | 
| Number of Participants With Evaluated Laboratory Abnormalities After Vaccination With ACAM FLU A, or ACAM FLU A With Adjuvant, or Placebo Vaccine. |  | Day 0 through Day 60 post-vaccination 1 | 
| Number of Participants With Seroconversion to M2e Antigen During Initial Treatment and Follow Up Period After Vaccination With ACAM FLU A, or ACAM FLU A With Adjuvant, or Placebo Vaccine | Seroconversion was defined as an end point anti M2e antibody titer ≥ 100. Antibody responses were assessed by means of enzyme linked immunosorbent assay (ELISA) | Day 15 through Month 10 Post-vaccination 1 | 
| Geometric Mean Titers (GMTs) of Vaccine Antibodies After Vaccination With ACAM FLU A, or ACAM FLU A With Adjuvant, or a Placebo Vaccine. | Antibody responses to the respective vaccines were assessed by means of enzyme linked immunosorbent assay (ELISA). A GMT value of 50.0 indicates a titer at or below the lowest limit of quantitation (LLOQ) | Day 15 through Month 10 Post-vaccination 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Signs and Symptoms of Influenza After Vaccination With ACAM FLU A, or ACAM FLU A With Adjuvant, or Placebo Vaccine. | Participants who reported signs and symptoms of influenza were tested using nasal pharyngeal swabs, with secretions cultured using susceptible tissue culture cell lines. Positive cultures were confirmed as influenza using immunofluorescence techniques with influenza strain specific antibodies. | Month 4 through Month 10 post-vaccination 1 | 
| Number of Participants With Seroconversion to M2e Antigen by Immunoglobulin G (IgG) Subclasses Before and Post-Vaccination With ACAM FLU A, or ACAM FLU A With Adjuvant, or Placebo Vaccine. | Seroconversion was defined as an antibody Titer ≥ 100. Antibody responses were assessed by means of enzyme linked immunosorbent assay (ELISA) | Day 0 and Day 60 Post-vaccination 1 | 
| Geometric Mean Titers of Anti-M2e Antigen by Immunoglobulin G (IgG) Subclasses Before and Post-Vaccination With ACAM FLU A, or ACAM FLU A With Adjuvant, or Placebo Vaccine. | Antibody responses were assessed by means of enzyme linked immunosorbent assay (ELISA). A GMT value of 50.0 indicates a titer at or below the lowest limit of quantitation (LLOQ). | Day 0 and Day 60 Post-vaccination 1 | 
| Geometric Mean Titer Ratios of Anti-M2e Antigen by Immunoglobulin G (IgG) Subclasses Before and Post-Vaccination With ACAM FLU A, or ACAM FLU A With Adjuvant, or Placebo Vaccine. | Antibody responses were assessed by means of enzyme linked immunosorbent assay (ELISA). | Day 0 and Day 60 Post-vaccination 1 | 
| Geometric Mean Titers (GMTs) of Anti-Hepatitis B Core Antibodies Using Immunoglobulin G (IgG) ELISA Before and Post-Vaccination With ACAM FLU A, or ACAM FLU A With Adjuvant, or Placebo Vaccine. | Antibody responses were assessed by means of enzyme linked immunosorbent assay (ELISA) | Day 0 and Day 15 through Month 10 post-vaccination 1 | 
| Number of Participants With Seropositivity to Hepatitis B Core Antigen Pre- and Post-Vaccination 1 With ACAM FLU A, or ACAM FLU A With Adjuvant, or Placebo Vaccine. | Seropositivity with ELISA was defined as a Pre- or post-vaccination antibody titer ≥ 100. Seropositivity with the Commercial Kit method was defined as a positive pre- or post-vaccination response. Seropositivity were assessed by means of enzyme linked immunosorbent assay (ELISA) and the Commercial Kit methods | Day 0 and Day 15 through Month 10 Post-vaccination 1 |