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

NCT01625689 | Completed Phase 2 Results DMC

• 1 other identifier: LAIV-BD-01
• Study Type: interventional
• Target: 309
• Locations: 1 country
• Sites: 1

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.

Conditions

Influenza

Keywords

Influenza vaccines; Influenza, Human; Live Attenuated Influenza Vaccine

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (4)

• 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

Study Arms (2)

SIIL LAIV

EXPERIMENTAL

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)

Placebo

PLACEBO COMPARATOR

Placebo identical in appearance to experimental vaccine.

Biological: Placebo

Interventions

SIIL LAIV (live, trivalent seasonal influenza vaccine) BIOLOGICAL

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

SIIL LAIV

Placebo BIOLOGICAL

Inactive placebo will be identical to SII LAIV in appearance, ingredients, and concentrations, except it will be missing attenuated influenza virus.

Placebo

Eligibility Criteria

• Age: 24 Months - 59 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• PATH Vaccine Solutions: lead
• Johns Hopkins Bloomberg School of Public Health: collaborator
• International Centre for Diarrhoeal Disease Research, Bangladesh: collaborator

Study Sites (1)

ICDDR,B Kamalapur

Dhaka, Bangladesh

Location

Related Publications (2)

• 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.

  PMID: 30481272 DERIVED

• 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.

  PMID: 30481269 DERIVED

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Senior Clinical Research Scientist
• Organization: PATH

klewis@path.org

206-285-3500

Study Officials

• W. Abdullah Brooks, MD, MPH

  JHSPH, ICDDR,B

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2012
• First Posted: June 21, 2012
• Study Start: June 1, 2012
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2013
• Last Updated: June 1, 2015
• Results First Posted: June 1, 2015

Record last verified: 2012-06

Locations

BA (1)