A Randomized, Controlled Trial on the Efficacy and Safety of Live-Attenuated Influenza Vaccine (LAIV) Among Children in Bangladesh
Condition: Influenza
MeSH terms: Influenza, Human
Intervention: SIIL Live Attenuated Influenza Vaccine; Placebo
Intervention description: 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; 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.
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1761.0
Sex: All
Minimum age: 24 Months
Maximum age: 59 Months
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      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:

        1. 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.

        2. Knowledge gap: There has never been a randomized clinical efficacy trial of the SIIL
           LAIV vaccine conducted among children in a low-income country.

        3. 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.
    

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 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