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

Assessment of the Safety and Immunogenicity of a Single Dose of Intranasal Seasonal Trivalent Live-Attenuated Influenza Vaccine Among Children Aged 24 Through 59 Months in Bangladesh

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.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: SIIL LAIV (live, trivalent seasonal influenza vaccine); Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 309
• Phase: Phase 2

Contacts and Locations

Study Locations

• Bangladesh
  • Dhaka, Bangladesh
    • Icddr,b Kamalapur

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 4 years (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SIIL LAIV; 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	Biological: SIIL LAIV (live, trivalent seasonal influenza vaccine); Dose: 0.5 mL, 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_COMPARATOR: Placebo; Placebo identical in appearance to experimental vaccine.	Biological: Placebo; Inactive placebo will be identical to SII LAIV in appearance, ingredients, and concentrations, except it will be missing attenuated influenza virus.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Serious Adverse Events (SAEs), All-cause Hospitalizations, and Protocol-defined Wheezing Illness (PDWI) Episodes	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	6 months following vaccination
Number of Participants With Serious Adverse Events (SAEs), All-cause Hospitalizations, and Protocol-defined Wheezing Illness (PDWI) Episodes	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	42 days following vaccination
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	Local reactions: Nasal discomfort, Runny nose, Stuffy nose, Sneezing, Ear pain Systemic Reactions: Cough, Headache, Loss of Appetite, Fever, Irritability, Nausea, Sore throat, Lethargy	Through 7 days following vaccination

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: PATH Vaccine Solutions
• Collaborators: Johns Hopkins Bloomberg School of Public Health; International Centre for Diarrhoeal Disease Research, Bangladesh
• Investigators: Principal Investigator: W. Abdullah Brooks, MD, MPH, JHSPH, ICDDR,B

Publications and helpful links

General Publications

• Lewis KDC, Ortiz JR, Rahman MZ, Levine MZ, Rudenko L, Wright PF, Katz JM, Dally L, Rahman M, Isakova-Sivak I, Ilyushina NA, Matyushenko V, Fry AM, Lindstrom SE, Bresee JS, Brooks WA, Neuzil KM. Immunogenicity and Viral Shedding of Russian-Backbone, Seasonal, Trivalent, Live, Attenuated Influenza Vaccine in a Phase II, Randomized, Placebo-Controlled Trial Among Preschool-Aged Children in Urban Bangladesh. Clin Infect Dis. 2019 Aug 16;69(5):777-785. doi: 10.1093/cid/ciy1003.
• Brickley EB, Wright PF, Khalenkov A, Neuzil KM, Ortiz JR, Rudenko L, Levine MZ, Katz JM, Brooks WA. The Effect of Preexisting Immunity on Virus Detection and Immune Responses in a Phase II, Randomized Trial of a Russian-Backbone, Live, Attenuated Influenza Vaccine in Bangladeshi Children. Clin Infect Dis. 2019 Aug 16;69(5):786-794. doi: 10.1093/cid/ciy1004.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (ACTUAL): February 1, 2013
• Study Completion (ACTUAL): February 1, 2013

Study Registration Dates

• First Submitted: June 14, 2012
• First Submitted That Met QC Criteria: June 19, 2012
• First Posted (ESTIMATE): June 21, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): June 1, 2015
• Last Update Submitted That Met QC Criteria: May 15, 2015
• Last Verified: June 1, 2012

More Information

Terms related to this study

• Keywords: Influenza, Human; Live Attenuated Influenza Vaccine; Influenza vaccines
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human
• Other Study ID Numbers: LAIV-BD-01