Clinical trial NCT01625689: Safety and Immunogenicity of a Single Dose of Intranasal Seasonal Trivalent Live-Attenuated Influenza Vaccine
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Influenza
Keywords: Influenza vaccines
Influenza, Human
Live Attenuated Influenza Vaccine
Lead sponsor: PATH
Sponsor class: OTHER
Collaborators: name: Johns Hopkins Bloomberg School of Public Health
name: International Centre for Diarrhoeal Disease Research, Bangladesh
First posted: 2012-06-21
Enrollment: 309
Sex: ALL
Minimum age (years): 24
Maximum age (years): 59
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.


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 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

Primary outcomes:
measure: Number of Participants With Serious Adverse Events (SAEs), All-cause Hospitalizations, and Protocol-defined Wheezing Illness (PDWI) Episodes
timeFrame: 6 months following vaccination
measure: Number of Participants With Serious Adverse Events (SAEs), All-cause Hospitalizations, and Protocol-defined Wheezing Illness (PDWI) Episodes
timeFrame: 42 days following vaccination
measure: Percentage of Participants With Unsolicited Adverse Events (AEs)
timeFrame: Throughout study period, through at least 6 months following vaccination
measure: Percentage of Participants With Solicited Local and Systemic Reactions
timeFrame: Through 7 days following vaccination
Secondary outcomes:
measure: 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
timeFrame: Approximately 21 days post-vaccination
measure: Post Vaccination SIIL LAIV Virus Shedding/Vaccine-take Will be Parameterized by the Percentage of Participants With Detectable Virus by Post Vaccination Day.
timeFrame: 2, 4, and 7 days post-vaccination
measure: 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
timeFrame: 6 months post-vaccination
measure: 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
timeFrame: 6 months post-vaccination
Other outcomes:
Locations:
city: Dhaka
country: Bangladesh
facility: ICDDR,B Kamalapur
Study officials:
affiliation: JHSPH, ICDDR,B
name: W. Abdullah Brooks, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.