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

Influenza Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01797029
• Other study ID #: LAIV-CE-01
• Status: Completed
• Phase: Phase 3
• First received: February 20, 2013
• Last updated: May 15, 2015
• Start date: February 2013
• Est. completion date: September 2014

Study information

• Verified date: July 2014
• Source: PATH
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Western Institutional Review BoardBangladesh: icddr,b Ethical Review Committee
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1761
• Est. completion date: September 2014
• Est. primary completion date: September 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 24 Months to 59 Months

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 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

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
• 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.

Locations

Country	Name	City	State
Bangladesh	icddr, b Kamalapur	Dhaka
Bangladesh	icddr,b Matlab	Matlab

Sponsors (5)

Lead Sponsor	Collaborator
PATH	Bill and Melinda Gates Foundation, Centers for Disease Control and Prevention, International Centre for Diarrhoeal Disease Research, Bangladesh, Johns Hopkins University

Country where clinical trial is conducted

Bangladesh, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants With Moderate to Severe, Laboratory-confirmed Influenza Virus Infection Among Children		Through 7 to 9 months post-vaccination	No
Other	Percentage of Participants With Moderate to Severe, Laboratory-confirmed Influenza Virus Infection Among Children		Through 16 to 19 months post-vaccination	No
Other	Percentage of Participants With Symptomatic, Laboratory-confirmed Influenza Virus Infection (Vaccine-matched Strains) Among Children		From approx. 6 months to approximately 19 months post-vaccination	No
Other	Percentage of Participants With Symptomatic, Laboratory-confirmed Influenza Virus Infection (All Strains) Among Children		From approx. 6 months to approximately 19 months post-vaccination	No
Primary	Percentage of Participants With Symptomatic, Laboratory-confirmed Influenza Virus Infection (Vaccine-matched Strains).		Through 7 to 9 months post-vaccination	No
Secondary	Safety Profile of LAIV: Solicited and Unsolicited Local and Systemic Reactions		Through one week post-vaccination	Yes
Secondary	Safety Profile of LAIV: Immediate Reactions		30 minutes post-vaccination	Yes
Secondary	Safety Profile of LAIV: Serious Adverse Events		Through 7 to 9 months post-vaccination	Yes
Secondary	Safety Profile of LAIV: Protocol Defined Wheezing Illness		Through 7 to 9 months post-vaccination	Yes
Secondary	Percentage of Participants With Symptomatic, Laboratory-confirmed, Influenza Virus Infection (All Strains)		Through 7 to 9 months post-vaccination	No
Secondary	The Clinical Characteristics of Influenza, Including Influenza Co-infections With Other Bacterial and Viral Respiratory Pathogens		Through 16 to 19 months post-vaccination	No
Secondary	The Viral Etiologies of Acute Respiratory and Febrile Illness		Through 16 to 19 months post-vaccination	No
Secondary	Safety Profile of LAIV: Serious Adverse Events		Through 16 to 19 months post-vaccination	Yes
Secondary	Safety Profile of LAIV: Protocol Defined Wheezing Illness		Through 16 to 19 months post-vaccination	Yes
Secondary	Percentage of Participants With Symptomatic, Laboratory-confirmed, Influenza Virus Infection (All Strains)		Through 16 to 19 months post-vaccination	No
Secondary	Percentage of Participants With Symptomatic, Laboratory-confirmed Influenza Virus Infection (Vaccine-matched Strains).		Through 16 to 19 months post-vaccination	No