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

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.

Conditions

• Influenza

Interventions

BIOLOGICAL

SIIL Live Attenuated Influenza Vaccine

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

BIOLOGICAL

Placebo

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.

Sponsors & Collaborators

• Johns Hopkins University

  collaborator OTHER

• International Centre for Diarrhoeal Disease Research, Bangladesh

  collaborator OTHER

• Centers for Disease Control and Prevention

  collaborator FED

• Bill and Melinda Gates Foundation

  collaborator OTHER

• PATH

  lead OTHER

Principal Investigators

• Abdullah Brooks, MD, MPH · Johns Hopkins University

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

24 Months

Max Age

59 Months

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2013-02-28

Primary Completion

2014-09-30

Completion

2014-09-30

Countries

• Bangladesh

Study Locations