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

This study has been completed.
Sponsor:
Collaborators:
Johns Hopkins Bloomberg School of Public Health
International Centre for Diarrhoeal Disease Research, Bangladesh
Information provided by (Responsible Party):
PATH ( PATH Vaccine Solutions )
ClinicalTrials.gov Identifier:
NCT01625689
First received: June 14, 2012
Last updated: February 5, 2013
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Influenza
Biological: SIIL LAIV (live, trivalent seasonal influenza vaccine)
Biological: Placebo
Phase 2

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

Resource links provided by NLM:


Further study details as provided by PATH:

Primary Outcome Measures:
  • Number of serious adverse events (SAEs), all-cause hospitalizations, and protocol-defined wheezing illness (PDWI) episodes [ Time Frame: 6 months following vaccination ] [ Designated as safety issue: Yes ]

    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


  • Number of serious adverse events (SAEs), all-cause hospitalizations, and protocol-defined wheezing illness (PDWI) episodes [ Time Frame: 42 days following vaccination ] [ Designated as safety issue: Yes ]

    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


  • Number of unsolicited reactions [ Time Frame: 8 days through 6 months following vaccination ] [ Designated as safety issue: Yes ]
  • Number of solicited and unsolicited local and systemic reactions [ Time Frame: Through 7 days following vaccination ] [ Designated as safety issue: Yes ]

    Local reactions: Nasal discomfort, Runny nose, Stuffy nose, Sneezing, Ear pain

    Systemic Reactions: Cough, Headache, Loss of Appetite, Fever, Irritability, Nausea, Sore throat, Lethargy



Secondary Outcome Measures:
  • 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 [ Time Frame: Approximately 21 days post-vaccination ] [ Designated as safety issue: No ]
  • Post vaccination SII LAIV virus shedding/vaccine-take will be parameterized by the percentage of participants with detectable virus by post vaccination day. [ Time Frame: 2, 4, and 7 days post-vaccination ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 6 months post-vaccination ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 6 months post-vaccination ] [ Designated as safety issue: No ]

Enrollment: 309
Study Start Date: June 2012
Study Completion Date: February 2013
Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   24 Months to 59 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01625689

Locations
Bangladesh
ICDDR,B Kamalapur
Dhaka, Bangladesh
Sponsors and Collaborators
PATH Vaccine Solutions
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
  More Information

No publications provided

Responsible Party: PATH ( PATH Vaccine Solutions )
ClinicalTrials.gov Identifier: NCT01625689     History of Changes
Other Study ID Numbers: LAIV-BD-01
Study First Received: June 14, 2012
Last Updated: February 5, 2013
Health Authority: United States: Western Institutional Review Board (WIRB)
Bangladesh: ICDDR,B Ethical Review Committee
Bangladesh: Bangladesh Drug Administration

Keywords provided by PATH:
Influenza vaccines
Influenza, Human
Live Attenuated Influenza Vaccine

Additional relevant MeSH terms:
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 11, 2014