A Randomized, Controlled Trial on the Efficacy and Safety of Live-Attenuated Influenza Vaccine (LAIV) Among Children in Bangladesh

Study Overview
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Brief Summary
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This is a single center, multi-site, double-blind, parallel group, placebo-controlled trial of the clinical efficacy of trivalent Serum Institute of India, Ltd. (SIIL)live-attenuated influenza vaccine (LAIV) vaccine among children aged 24 through 59 months in Bangladesh. Background: Burden: Within Bangladesh, community- based influenza surveillance identified 84.5 cases/1000 children-years among children <5 years, while 10% of clinical pneumonia cases were influenza positive in this age group. Knowledge gap: There has never been a randomized clinical efficacy trial of the SIIL LAIV vaccine conducted among children in a low-income country. Relevance: Another LAIV vaccine (made by MedImmune) has been shown to have high efficacy against laboratory-confirmed influenza among children. The SIIL LAIV has the potential to be an inexpensive intervention to prevent pediatric influenza disease. Primary Hypothesis: In children aged 24 through 59 months in Bangladesh, LAIV is efficacious in reducing rates of symptomatic, laboratory-confirmed influenza (vaccine-matched strains) among children vaccinated with LAIV as compared to children vaccinated with a placebo through the first influenza season following vaccination. Primary Objective: To determine the efficacy of LAIV in reducing rates of symptomatic, laboratory-confirmed influenza virus infection (vaccine-matched strains) among children receiving LAIV as compared to children receiving a placebo through the first influenza season following vaccination (through December 2013). Methods: A total of 1761 children will be enrolled and randomized in a 2:1 ratio of LAIV to placebo beginning in March 2013. After vaccination, all children will be evaluated for reactions with one home visit four days post vaccination. Subsequently, all children will be monitored weekly for safety outcomes and illness signs at weekly field worker home visits through December 2013. An extended surveillance period was added to this study and, for participants consenting to additional follow-up, surveillance will extend through a second season (through September 2014). Participants with illness signs will be referred to the study clinic for evaluation using standardized diagnostic criteria and treatment by a study physician. Children meeting protocol-defined clinical Specimen Collection Criteria will have a nasopharyngeal wash specimen collected. Clinical specimens will be tested by Real time polymerase chain reaction (rRT-PCR) for evidence of influenza virus infection. Primary Outcome measures/variables: Vaccine efficacy will be assessed against symptomatic, laboratory-confirmed influenza for all circulating virus strains.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Trial on the Clinical Efficacy and Safety of a Single Dose of Trivalent Seasonal Live-Attenuated Influenza Vaccine(LAIV) Among Children Aged 24 Through 59 Months in Bangladesh

Conditions
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Influenza

Intervention / Treatment
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* Biological: SIIL Live Attenuated Influenza Vaccine
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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 or Matlab service 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, active, medical conditions, including: a chronic disease of any body system, chronic infections such as tuberculosis, genetic disorders, such as Down's syndrome or other cytogenetic disorder, known or suspected disease of the immune system. Is receiving immunosuppressive agents, including systemic corticosteroids, during the month 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. Has ever received influenza vaccine (LAIV or inactivated). History of Guillain-Barre syndrome 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. History of a previous severe allergic reaction with generalized urticarial, angioedema, or anaphylaxis. 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 or make it unlikely that the child would complete the study Temporary Inclusion Contraindications: Concurrent febrile illness (measured temperature 38 degrees C axillary). Active wheezing illness

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

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: Vaccine<br> | Biological: SIIL Live Attenuated Influenza Vaccine<br>* A single dose of SIIL Trivalent LAIV--2012/2013 Northern Hemisphere vaccine containing A/California/7/2009 (H1N1), A/Victoria/361/2011 (H3N2), B/Wisconsin/1/2010<br>|
| Placebo Comparator: Placebo<br> | Biological: Placebo<br>* A single dose of inactive placebo will be identical to reconstituted SIIL LAIV in ingredients and concentrations except A/California/7/2009 (H1N1), A/Victoria/361/2011 (H3N2), B/Wisconsin/1/2010 will be replaced with egg allantoic fluid.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Symptomatic, Laboratory-confirmed Influenza Virus Infection (Vaccine-matched Strains). |  | Through 7 to 9 months post-vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Profile of LAIV: Solicited and Unsolicited Local and Systemic Reactions |  | Through one week post-vaccination | 
| Safety Profile of LAIV: Immediate Reactions |  | 30 minutes post-vaccination | 
| Safety Profile of LAIV: Serious Adverse Events |  | Through 7 to 9 months post-vaccination | 
| Safety Profile of LAIV: Protocol Defined Wheezing Illness |  | Through 7 to 9 months post-vaccination | 
| Percentage of Participants With Symptomatic, Laboratory-confirmed, Influenza Virus Infection (All Strains) |  | Through 7 to 9 months post-vaccination | 
| The Clinical Characteristics of Influenza, Including Influenza Co-infections With Other Bacterial and Viral Respiratory Pathogens |  | Through 16 to 19 months post-vaccination | 
| The Viral Etiologies of Acute Respiratory and Febrile Illness |  | Through 16 to 19 months post-vaccination | 
| Safety Profile of LAIV: Serious Adverse Events |  | Through 16 to 19 months post-vaccination | 
| Safety Profile of LAIV: Protocol Defined Wheezing Illness |  | Through 16 to 19 months post-vaccination | 
| Percentage of Participants With Symptomatic, Laboratory-confirmed, Influenza Virus Infection (All Strains) |  | Through 16 to 19 months post-vaccination | 
| Percentage of Participants With Symptomatic, Laboratory-confirmed Influenza Virus Infection (Vaccine-matched Strains). |  | Through 16 to 19 months post-vaccination |