Reactogenicity, Safety and Immunogenicity of a Live Monovalent A/17/CALIFORNIA/66/395 (H2N2) Influenza Vaccine

Study Overview
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Brief Summary
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This is a phase I study to evaluate the safety of a vaccine to protect against influenza viruses of the H2N2 subtype. A total of 40 adults will be enrolled and receive two doses of vaccine or placebo one month apart.

Detailed Description
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The aim of this study is to evaluate the safety profile of two intranasal doses of LAIV A/17/California/66/395 (H2N2) in healthy adults in Russia. A(H2N2) viruses which are antigenically similar to the pandemic strain A/Singapore/1/57, continue to circulate in domestic and wild bird populations, as confirmed by routine moni¬toring of avian influenza viruses. 40 adults aged 18-40 will be enrolled. They will be randomized to receive vaccine or placebo. Blood and urine will be collected during the week following each vaccination and before the next vaccination to monitor safety. Blood samples will also be collected at several timepoints to assess the volunteer's immune response to the vaccine. The total duration of the study is 16 weeks for each volunteer.

Official Title
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Reactogenicity, Safety and Immunogenicity of a Live Monovalent A/17/California/66/395 (H2N2)Influenza Vaccine

Conditions
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Influenza

Intervention / Treatment
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* Biological: LAIV H2N2
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Legal male or female adult aged 18 through 40 years Literate and willing to provide written informed consent. A signed informed consent. Free of obvious health problems, as established by 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 isolation unit (including willing and able to take oseltamivir influenza antiviral medication, should that be recommended by study physician). For females, willing to take reliable birth control measures through day 56. Exclusion Criteria: Participation in another clinical trial involving any therapy within the previous three months or planned enrollment in such a trial during trial period. 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 during period of subject participation in the study. Chronic administration (defined as more than 14 consecutively-prescribed days) of immunosuppressants and/or other immune-modulating therapy within six months prior to study enrollment. Participation in any previous trial of any H2N2 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 (body temperature more than 40°C, collapse, non-febrile seizures, anaphylaxis), at least possibly related to previous receipt of any vaccine (not only influenza). Suspected or known hypersensitivity to any 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 virus (HBV) or hepatitis C virus (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. Any condition that, in the opinion of the investigator, would increase the health risk to the subject if participates in the study or would interfere with the evaluation of the study objectives. Allergic, including anaphylactic, reactions to the introduction of any vaccines (not only influenza) in the subject's medical history

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LAIV H2N2 vaccine<br>LAIV H2N2 vaccine A/17/California/66/395 (H2N2) live monovalent influenza vaccine delivered intranasally 2 doses 1 month apart | Biological: LAIV H2N2<br>* vaccine is delivered intranasally, .25 cc to each nostril at day 0 and day 28<br>* Other names: Monovalent A/17/California/66/395 (LAIV H2N2) vaccine;|
| Placebo Comparator: Placebo<br>Placebo is composed of a lyophilizate containing the same concentrations of stabilizers as LAIV vaccine. It is prepared onsite in an identical fashion to the vaccine and delivered intranasally. | Other: Placebo<br>* placebo delivered intranasally. .25cc to each nostril at day 0 and day 28<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Immediate Reactions | Measured as observed by study staff or reported by the subject to study staff whether related or not related. | 2 hours | 
| Percentage of Subjects With Solicited Local and Systemic Reactions After Vaccination 1 | Adverse events commonly associated with intranasal vaccination occurring greater than two hours after administration of any dose of study vaccine or placebo through 6 days following any dose, measured as observed by study staff or reported by the subject to study staff. Solicited local reactions included: dryness of the nose, nose bleeds, ticklish nose, nasal congestion, runny nose, ticklish throat, catarrhal nasopharynx. Solicited systemic reactions included: body temperature, feverishness/subjective fever, chills, cough, difficulty breathing, sore throat, headache, confusion, convulsions/seizures, fatigue/malaise, joint aches, muscle aches, pink or red eyes, draining eyes, swollen eyelids, ear pain or discharge, rash, abdominal pain, diarrhea, vomiting. | 7 days | 
| Percentage of Subjects With Solicited Local and Systemic Reactions After Vaccination 2 | Adverse events commonly associated with intranasal vaccination occurring greater than two hours after administration of any dose of study vaccine or placebo through 6 days following any dose, measured as observed by study staff or reported by the subject to study staff. Solicited local reactions included: dryness of the nose, nose bleeds, ticklish nose, nasal congestion, runny nose, ticklish throat, catarrhal nasopharynx. Solicited systemic reactions included: body temperature, feverishness/subjective fever, chills, cough, difficulty breathing, sore throat, headache, confusion, convulsions/seizures, fatigue/malaise, joint aches, muscle aches, pink or red eyes, draining eyes, swollen eyelids, ear pain or discharge, rash, abdominal pain, diarrhea, vomiting. | 7 days | 
| Percentage of Subjects With Unsolicited Adverse Events After Vaccination 1 | All other adverse events (including unsolicited events and abnormal laboratory parameters) occurring during the 6 days following any dose, measured as observed by study staff or reported by the subject to study staff. | 7 days following each vaccination | 
| Percentage of Subjects With Unsolicited Adverse Events After Vaccination 2 | All other adverse events (including unsolicited events and abnormal laboratory parameters) occurring during the 6 days following any dose, measured as observed by study staff or reported by the subject to study staff. | 7 days following each vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Seroconversion for Serum Hemagglutination Inhibition (HAI) Antibodies | Defined as a 4-fold or higher response from baseline (day 0), 28 days after each vaccination and after 112 days. | Day 28, Day 56 and Day 112 | 
| Percentage of Subjects With Seroconversion for Serum Neutralizing Antibodies | Defined as a 4-fold or higher response from baseline (day 0), 28 days after each vaccination and after 112 days. Measured by microneutralization assay. | Day 28, Day 56 and Day 112 | 
| Percentage of Subjects With Seroconversion for Serum Immunoglobulin A Antibodies | Defined as a 4-fold or higher response from baseline (day 0), 28 days after each vaccination and after 112 days. Measured by enzyme-linked immunosorbent assay (ELISA). | Day 28, Day 56 and Day 112 | 
| Percentage of Subjects With Seroconversion for Serum Immunoglobulin G Antibodies | Defined as a 4-fold or higher response from baseline (day 0), 28 days after each vaccination and after 112 days. Measured by enzyme-linked immunosorbent assay (ELISA). | Day 28, Day 56 and Day 112 | 
| Percentage of Subjects With Seroconversion for Secretory Immunoglobulin A Antibodies From Nasal Mucosa | Defined as a 4-fold or higher response from baseline (day 0), 28 days after each vaccination. | Day 28 and Day 56 | 
| Percentage of Subjects With Seroconversion for Secretory Immunoglobulin A Antibodies Detected in Saliva Specimens | Defined as a 4-fold or higher response from baseline (day 0), 28 days after each vaccination. | Day 28 and Day 56 | 
| Percentage of Subjects Shedding Influenza A Virus Using Nasal Swab | Detected by real-time reverse transcriptase polymerase chain reaction. Specimens were collected prior to each vaccination and 7 days post-vaccination. | Days 0-6 and Days 28-34 | 
| Percentage of Subjects Shedding Influenza Virus Subtype Using Nasal Swab | Detected by real-time reverse transcriptase polymerase chain reaction. Specimens were collected prior to each vaccination and 7 days post-vaccination. | Days 0-6 and Days 28-34 | 
| Percentage of Subjects Shedding Influenza A Virus Using Throat Swab | Detected by real-time reverse transcriptase polymerase chain reaction. Specimens were collected prior to each vaccination and 7 days post-vaccination. | Days 0-6 and Days 28-34 | 
| Percentage of Subjects Shedding Influenza Virus Subtype Using Throat Swab | Detected by real-time reverse transcriptase polymerase chain reaction. Specimens were collected prior to each vaccination and 7 days post-vaccination. | Days 1-6 and Days 29-34 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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H2N2, vaccine