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

Phase 2

Completed

Interventions: Biological: SIIL LAIV (live, trivalent seasonal influenza vaccine)
Biological: Placebo

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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
SIIL LAIV	SIIL LAIV (live, trivalent seasonal influenza vaccine)	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
Placebo	Placebo	Placebo identical in appearance to experimental vaccine.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Serious Adverse Events (SAEs), All-cause Hospitalizations, and Protocol-defined Wheezing Illness (PDWI) Episodes	42 days following vaccination	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
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	Through 7 days following vaccination	Local reactions: Nasal discomfort, Runny nose, Stuffy nose, Sneezing, Ear pain Systemic Reactions: Cough, Headache, Loss of Appetite, Fever, Irritability, Nausea, Sore throat, Lethargy

Secondary Outcome Measures

Name	Time	Method
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