Reactogenicity, Safety, and Immunogenicity of a Live Monovalent H5N2 Influenza Vaccine

Study Overview
=================
Brief Summary
-----------------
To evaluate the safety profile of two intranasal doses of LAIV A/17/turkey/Turkey/05/133 (H5N2) in healthy adults.

Official Title
-----------------
Reactogenicity, Safety and Immunogenicity of a Live Monovalent A/17/Turkey/Turkey/05/133 (H5N2) Influenza Vaccine

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

Intervention / Treatment
-----------------
* Biological: LAIV H5N2
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Legal male or female adult 18 through 49 years of age at the enrollment visit. Literate and willing to provide written informed consent. Free of obvious health problems, as established by the medical history and screening evaluations, including physical examination. Capable and willing to complete diary cards and willing to return for all follow-up visits Willing to comply with the rules of the isolation unit (including willing and able to take oseltamivir influenza antiviral medication, should that be recommended by a study physician). For females, willing to take reliable birth control measures throughout the entire period of participation in the study. Exclusion Criteria: Participation in another clinical trial involving any therapy within the previous three months or planned enrollment in such a trial during the period of this study. Receipt of any non-study vaccine within four weeks prior to enrollment or refusal to postpone receipt of such vaccines until four weeks after study completion. Practice of nasal irrigation on a regular basis within the past six months or has engaged in nasal irrigation within two weeks prior to enrollment. Recent history of frequent nose bleeds (>5 within the past year). Clinically relevant abnormal paranasal anatomy. Recent history (within the past month) of rhino or sinus surgery, or surgery for any traumatic injury of the nose. Current or recent (within two weeks of enrollment) acute respiratory illness with or without fever. Other acute illness at the time of study enrollment. Receipt of immune globulin or other blood products within three months prior to study enrollment or planned receipt of such products during the period of subject participation in the study. Chronic administration (defined as more than 14 consecutively-prescribed days) of immunosuppressants or other immune-modulating therapy within six months prior to study enrollment. (For corticosteroids, this means prednisone or equivalent, 0.5 mg per kg per day; topical steroids are allowed, exclusive of nasal.) Participation in any previous trial of any H5 or H7 containing influenza vaccine. History of asthma. Hypersensitivity after previous administration of any influenza vaccine. History of wheezing after past receipt of any live influenza vaccine. Other adverse event (AE) following immunization, at least possibly related to previous receipt of any influenza vaccine. Suspected or known hypersensitivity to any of the study vaccine components, including chicken or egg protein. Seasonal (autumnal) hypersensitivity to the natural environment. Acute or chronic clinically significant pulmonary, cardiovascular, hepatic, metabolic, neurologic, psychiatric or renal functional abnormality, as determined by medical history, physical examination or clinical laboratory screening tests, which in the opinion of the investigator, might interfere with the study objectives. Subjects with physical examination findings or clinical laboratory screening results which would be graded 2 or higher on the AE severity grading scale (see Attachments) will be excluded from entry into the study and will be excluded from receipt of dose two of study vaccine or placebo. History of leukemia or any other blood or solid organ cancer. History of thrombocytopenic purpura or known bleeding disorder. History of seizures. Known or suspected immunosuppressive or immunodeficient condition of any kind, including HIV infection. Known chronic hepatitis B (HBV) or hepatitis C (HCV) infection. Known tuberculosis infection or evidence of previous tuberculosis exposure. History of chronic alcohol abuse and/or illegal drug use. Claustrophobia or sociophobia. Pregnancy or lactation. (A negative pregnancy test will be required before administration of study vaccine or placebo for all women of childbearing potential.) Any condition that, in the opinion of the investigator, would increase the health risk to the subject if he/she participates in the study or would interfere with the evaluation of the study objectives

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 49 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LAIV H5N2<br>Two doses of live monovalent influenza vaccine A/17/turkey/Turkey/05/133 ( live monovalent (LAIV H5N2) given intranasally | Biological: LAIV H5N2<br>* 2 doses provided intranasally<br>* Other names: A/17/turkey/Turkey/05/133(H5N2)live influenza vaccine;|
| Placebo Comparator: Placebo<br>two doses of placebo solution intranasal | Other: Placebo<br>* 2 doses of placebo provided intranasally<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events by Severity | Occurrence of participants with adverse events associated with intranasal administration, by worst grade of severity | 6 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number/Percentage of Subjects With Seroconversion for Serum Hemagglutination Inhibition (HAI) | Defined as a four-fold or greater antibody rise in titer from pre-vaccination level. HAI = hemagglutination-inhibition, conducted using World Health Organization (WHO)-recommended protocols. | 28 days (Dose 1) and 56 days (Dose 2) | 
| Number/Percentage of Subjects With Serum Neutralizing Antibodies | Defined as a four-fold or greater antibody rise in titer from pre-vaccination level. Measured by microneutralization assay in Madin-Darby canine kidney cells (MDCK). | 28 days (Dose 1) and 56 days (Dose 2) | 
| Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin A (IgA) | IgA = immunoglobulin class A antibodies Determined using ELISA using whole purified H5N2 | 28 days (Dose 1) and 56 days (Dose 2) | 
| Number/Percentage of Subjects With Seroconversion for Serum Immunoglobulin G (IgG) | Determined using ELISA using whole purified H5N2. | 28 days (Dose 1) and 56 days (Dose 2) | 
| Number/Percentage of Subjects With Seroconversion for Secretory IgA | IgA antibodies from the nasal mucosa detected in nasal wick specimens. Determined using ELISA using whole purified H5N2 | 28 days (Dose 1) and 56 days (Dose 2) | 
| Number/Percentage of Subjects With Seroconversion for IgA in Saliva | IgA = Immunoglobulin Class A antibodies. Determined using ELISA using whole purified H5N2. | 28 days (Dose 1) and 56 days (Dose 2) | 
| Number/Percentage of Vaccinated Participants Shedding Influenza Virus After First Dose | Nasal swabs were collected and used for Reverse transcription polymerase chain reaction (rRTPCR) assays to detect shedding of influenza virus for days 1-6 of the study. | 6 days post-vaccination | 
| Number/Percentage of Vaccinated Participants Shedding Influenza Virus After Second Dose | Nasal swabs were collected and used for Reverse transcription polymerase chain reaction (rRTPCR) assays to detect shedding of influenza virus for days 29-34 of the study (6 days after the second vaccination). | 6 days post-vaccination | 
| Geometric Mean Titers for Serum HAI Antibodies | Geometric mean titers for serum hemagglutination inhibition antibodies | 0 days, 28 days (Dose 1) and 56 days (Dose 2) | 
| Geometric Mean Titers (GMT) for Serum Neutralizing Antibodies | Geometric mean titers for serum neutralizing antibodies measured by microneutralization assay | 0 days, 28 days (Dose 1) and 56 days (Dose 2) | 

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