Safety and Immunogenicity of a Single Dose of Intranasal Seasonal Trivalent Live-Attenuated Influenza Vaccine

Study Overview
=================
Brief Summary
-----------------
In this Phase II randomized controlled clinical trial, generally healthy male and female children from 24 through 59 months of age will be enrolled in Kamalapur (Dhaka), Bangladesh. The study is expected to continue for at least 6 months following vaccination. The experimental intervention is Serum Institute of India Ltd's Trivalent, Seasonal Live Attenuated Influenza Vaccine (SIIL LAIV). The study vaccine has been formulated according to WHO recommendations for the 2011-2012 Northern Hemisphere influenza season. The SIIL LAIV is administered in a 0.5 ml intranasal dose (one spray of 0.25 ml per nostril) via a reusable sprayer device and a single-use nozzle that produces a fine mist that is primarily deposited in the nose and nasopharynx. The comparator vaccine will be an inactive placebo identical in appearance to the active vaccine. The primary study hypothesis is that LAIV is safe and well tolerated by children aged 24 through 59 months in Bangladesh. A secondary hypothesis is that LAIV is immunogenic among children receiving study vaccine as compared to children receiving placebo.

Official Title
-----------------
Assessment of the Safety and Immunogenicity of a Single Dose of Intranasal Seasonal Trivalent Live-Attenuated Influenza Vaccine Among Children Aged 24 Through 59 Months in Bangladesh

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

Intervention / Treatment
-----------------
* Biological: SIIL LAIV (live, trivalent seasonal influenza vaccine)
* Biological: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Healthy male or female child at least 24 months of age and no older than 59 months of age at the time of study vaccination A child whose parent or guardian's primary residence, at the time of study vaccinations, is within the Kamalapur surveillance site catchment area and who intends to be present in the area for the duration of the trial A child whose parent or legal guardian is willing to provide written informed consent prior to the participant's study vaccination Exclusion Criteria: Has any serious chronic disease including progressive neurologic disease, tuberculosis, Down's syndrome or other cytogenetic disorder, or known or suspected disease of the immune system Is receiving immunosuppressive agents including systemic corticosteroids during the two weeks prior to study vaccination Has a history of documented hypersensitivity to eggs or other components of the vaccine (including gelatin, sorbitol, lactalbumin and chicken protein), or with life-threatening reactions to previous influenza vaccinations Is receiving aspirin therapy or aspirin-containing therapy currently or two weeks before Lives in household with somebody currently participating in a respiratory vaccination or antiviral study Has current or past participation (within 2 months of trial enrollment visit) in any clinical trial involving a drug or biologic with activity against respiratory disease Has any condition determined by investigator as likely to interfere with evaluation of the vaccine or be a significant potential health risk to the child

Ages Eligible for Study
-----------------
Minimum Age: 24 Months
Maximum Age: 59 Months

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: SIIL LAIV<br>SII LAIV is a live, trivalent seasonal influenza vaccine. The viral strains in seasonal trivalent influenza vaccine (human, live attenuated) are antigenically similar to A/California/7/2009 (H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008 Type B, as per the WHO recommended strains for the Northern hemisphere 2011-12 influenza season | Biological: SIIL LAIV (live, trivalent seasonal influenza vaccine)<br>* Dose: 0.5 mL, The viral strains in seasonal trivalent influenza vaccine (human, live attenuated) are antigenically similar to A/California/7/2009 (H1N1), A/Perth/16/2009 (H3N2) and B/Brisbane/60/2008 Type B, as per the WHO recommended strains for the Northern hemisphere 2011-12 influenza season<br>|
| Placebo Comparator: Placebo<br>Placebo identical in appearance to experimental vaccine. | Biological: Placebo<br>* Inactive placebo will be identical to SII LAIV in appearance, ingredients, and concentrations, except it will be missing attenuated influenza virus.<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Serious Adverse Events (SAEs), All-cause Hospitalizations, and Protocol-defined Wheezing Illness (PDWI) Episodes | PDWI: Participants meeting illness criteria, seeking care in health facility, and with wheeze identified by a study physician Illness criteria: The presence of one Category A (Fever (>=38°C), tachypnea, danger signs (chest-indrawing, lethargy, cyanosis, inability to drink, convulsions), difficult breathing, noisy breathing, ear pain or discharge) or two Category B findings (Cough, rhinorrhea, sore throat, myalgia/arthralgia, chills, headache, irritability/decreased activity, vomiting) Wheeze: Long high-pitched whistling or musical sound on expiration heard by auscultation | 6 months following vaccination | 
| Number of Participants With Serious Adverse Events (SAEs), All-cause Hospitalizations, and Protocol-defined Wheezing Illness (PDWI) Episodes | PDWI: Participants meeting illness criteria, seeking care in health facility, and with wheeze identified by a study physician Illness criteria: The presence of one Category A (Fever (>=38°C), tachypnea, danger signs (chest-indrawing, lethargy, cyanosis, inability to drink, convulsions), difficult breathing, noisy breathing, ear pain or discharge) or two Category B findings (Cough, rhinorrhea, sore throat, myalgia/arthralgia, chills, headache, irritability/decreased activity, vomiting) Wheeze: Long high-pitched whistling or musical sound on expiration heard by auscultation | 42 days following vaccination | 
| Percentage of Participants With Unsolicited Adverse Events (AEs) |  | Throughout study period, through at least 6 months following vaccination | 
| Percentage of Participants With Solicited Local and Systemic Reactions | Local reactions: Nasal discomfort, Runny nose, Stuffy nose, Sneezing, Ear pain Systemic Reactions: Cough, Headache, Loss of Appetite, Fever, Irritability, Nausea, Sore throat, Lethargy | Through 7 days following vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Post-vaccination Anti-influenza Immunologic Response Will be Measured Based on the Type of Immunologic Assay and Categorized by Vaccine Virus Strain, Participant Baseline Serostatus, and Vaccine Allocation |  | Approximately 21 days post-vaccination | 
| Post Vaccination SIIL LAIV Virus Shedding/Vaccine-take Will be Parameterized by the Percentage of Participants With Detectable Virus by Post Vaccination Day. |  | 2, 4, and 7 days post-vaccination | 
| Clinical Characteristics of Influenza, Including Influenza Coinfections With Other Bacterial and Viral Respiratory Pathogens, Will be Parameterized as the Percentage of Participants Categorized by Vaccine Allocation |  | 6 months post-vaccination | 
| Viral Etiologies of Acute Respiratory and Febrile Illness Will be Parameterized as the Percentage of Those With Each Particular Laboratory-confirmed Respiratory Virus Infection Categorized by Vaccine Allocation |  | 6 months post-vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Influenza, Human, Live Attenuated Influenza Vaccine, Influenza vaccines