Influenza
Conditions
Keywords
Influenza vaccines, Influenza, Human, Live Attenuated Influenza Vaccine
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.
Interventions
BIOLOGICALSIIL 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
BIOLOGICALPlacebo
Inactive placebo will be identical to SII LAIV in appearance, ingredients, and concentrations, except it will be missing attenuated influenza virus.
Sponsors
Johns Hopkins Bloomberg School of Public Health
International Centre for Diarrhoeal Disease Research, Bangladesh
PATH Vaccine Solutions
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
24 Months to 59 Months
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Serious Adverse Events (SAEs), All-cause Hospitalizations, and Protocol-defined Wheezing Illness (PDWI) Episodes | 6 months following vaccination | 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 |
| 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 | Through 7 days following vaccination | 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
| 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 |
| 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 |
| 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 |
Countries
Bangladesh
Participant flow
Pre-assignment details
309 participants were consented and enrolled in the study. 9 participants were ineligible to receive study vaccination. 300 total participants were vaccinated and followed through the study period.
Participants by arm
| Arm | Count |
|---|---|
| SIIL LAIV The SIIL LAIV (human, live attenuated, trivalent seasonal influenza vaccine): The viral strains in 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 | 150 |
| Placebo Inactive placebo was identical to the SIIL LAIV in appearance, ingredients, and concentrations, except it was missing attenuated influenza virus. | 150 |
| Total | 300 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Migration | 2 | 1 |
Baseline characteristics
| Characteristic | SIIL LAIV | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 150 Participants | 150 Participants | 300 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Bangladesh | 150 participants | 150 participants | 300 participants |
| Sex: Female, Male Female | 73 Participants | 66 Participants | 139 Participants |
| Sex: Female, Male Male | 77 Participants | 84 Participants | 161 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 96 / 150 | 94 / 150 |
| serious Total, serious adverse events | 6 / 150 | 0 / 150 |
Outcome results
Primary
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
Time frame: 42 days following vaccination
Primary
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
Time frame: 6 months following vaccination
Population: Safety analysis population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SIIL LAIV | Number of Participants With Serious Adverse Events (SAEs), All-cause Hospitalizations, and Protocol-defined Wheezing Illness (PDWI) Episodes | Serious Adverse Events | 6 participants |
| SIIL LAIV | Number of Participants With Serious Adverse Events (SAEs), All-cause Hospitalizations, and Protocol-defined Wheezing Illness (PDWI) Episodes | Protocol Defined Wheezing Illness (PDWI) | 13 participants |
| SIIL LAIV | Number of Participants With Serious Adverse Events (SAEs), All-cause Hospitalizations, and Protocol-defined Wheezing Illness (PDWI) Episodes | Hospitalizations | 3 participants |
| Placebo | Number of Participants With Serious Adverse Events (SAEs), All-cause Hospitalizations, and Protocol-defined Wheezing Illness (PDWI) Episodes | Serious Adverse Events | 0 participants |
| Placebo | Number of Participants With Serious Adverse Events (SAEs), All-cause Hospitalizations, and Protocol-defined Wheezing Illness (PDWI) Episodes | Protocol Defined Wheezing Illness (PDWI) | 16 participants |
| Placebo | Number of Participants With Serious Adverse Events (SAEs), All-cause Hospitalizations, and Protocol-defined Wheezing Illness (PDWI) Episodes | Hospitalizations | 0 participants |
Primary
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
Time frame: Through 7 days following vaccination
Population: Safety analysis population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SIIL LAIV | Percentage of Participants With Solicited Local and Systemic Reactions | Ear pain | 1.3 percentage of participants |
| SIIL LAIV | Percentage of Participants With Solicited Local and Systemic Reactions | Headache | 0.7 percentage of participants |
| SIIL LAIV | Percentage of Participants With Solicited Local and Systemic Reactions | Runny nose/nasal congestion | 20.7 percentage of participants |
| SIIL LAIV | Percentage of Participants With Solicited Local and Systemic Reactions | Irritability/decreased activitity | 0.0 percentage of participants |
| SIIL LAIV | Percentage of Participants With Solicited Local and Systemic Reactions | Cough | 6.7 percentage of participants |
| SIIL LAIV | Percentage of Participants With Solicited Local and Systemic Reactions | Vomiting | 1.3 percentage of participants |
| SIIL LAIV | Percentage of Participants With Solicited Local and Systemic Reactions | Sore throat | 1.3 percentage of participants |
| SIIL LAIV | Percentage of Participants With Solicited Local and Systemic Reactions | Lethargy | 0.0 percentage of participants |
| SIIL LAIV | Percentage of Participants With Solicited Local and Systemic Reactions | Measured fever (>=38.0) | 3.3 percentage of participants |
| Placebo | Percentage of Participants With Solicited Local and Systemic Reactions | Lethargy | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Solicited Local and Systemic Reactions | Measured fever (>=38.0) | 3.3 percentage of participants |
| Placebo | Percentage of Participants With Solicited Local and Systemic Reactions | Ear pain | 1.3 percentage of participants |
| Placebo | Percentage of Participants With Solicited Local and Systemic Reactions | Cough | 5.3 percentage of participants |
| Placebo | Percentage of Participants With Solicited Local and Systemic Reactions | Runny nose/nasal congestion | 22.7 percentage of participants |
| Placebo | Percentage of Participants With Solicited Local and Systemic Reactions | Sore throat | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Solicited Local and Systemic Reactions | Headache | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Solicited Local and Systemic Reactions | Irritability/decreased activitity | 0.0 percentage of participants |
| Placebo | Percentage of Participants With Solicited Local and Systemic Reactions | Vomiting | 2.0 percentage of participants |
p-value: >=0.498Fisher Exact
Primary
Percentage of Participants With Unsolicited Adverse Events (AEs)
Time frame: Throughout study period, through at least 6 months following vaccination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| SIIL LAIV | Percentage of Participants With Unsolicited Adverse Events (AEs) | Oral thrush | 17.3 percentage of participants |
| SIIL LAIV | Percentage of Participants With Unsolicited Adverse Events (AEs) | Abdominal pain/distension | 3.3 percentage of participants |
| SIIL LAIV | Percentage of Participants With Unsolicited Adverse Events (AEs) | Helminthiasis | 6.0 percentage of participants |
| SIIL LAIV | Percentage of Participants With Unsolicited Adverse Events (AEs) | Allergy | 4.0 percentage of participants |
| SIIL LAIV | Percentage of Participants With Unsolicited Adverse Events (AEs) | Boil/abscess/skin infection/ulcer/cyst | 7.3 percentage of participants |
| SIIL LAIV | Percentage of Participants With Unsolicited Adverse Events (AEs) | Fungal Infection | 4.0 percentage of participants |
| SIIL LAIV | Percentage of Participants With Unsolicited Adverse Events (AEs) | Scabies | 5.3 percentage of participants |
| SIIL LAIV | Percentage of Participants With Unsolicited Adverse Events (AEs) | Other | 36.7 percentage of participants |
| SIIL LAIV | Percentage of Participants With Unsolicited Adverse Events (AEs) | Diarrheal Illness | 25.3 percentage of participants |
| Placebo | Percentage of Participants With Unsolicited Adverse Events (AEs) | Other | 34.0 percentage of participants |
| Placebo | Percentage of Participants With Unsolicited Adverse Events (AEs) | Diarrheal Illness | 21.3 percentage of participants |
| Placebo | Percentage of Participants With Unsolicited Adverse Events (AEs) | Oral thrush | 12.0 percentage of participants |
| Placebo | Percentage of Participants With Unsolicited Adverse Events (AEs) | Boil/abscess/skin infection/ulcer/cyst | 12.0 percentage of participants |
| Placebo | Percentage of Participants With Unsolicited Adverse Events (AEs) | Helminthiasis | 7.3 percentage of participants |
| Placebo | Percentage of Participants With Unsolicited Adverse Events (AEs) | Scabies | 4.0 percentage of participants |
| Placebo | Percentage of Participants With Unsolicited Adverse Events (AEs) | Abdominal pain/distension | 4.0 percentage of participants |
| Placebo | Percentage of Participants With Unsolicited Adverse Events (AEs) | Allergy | 4.0 percentage of participants |
| Placebo | Percentage of Participants With Unsolicited Adverse Events (AEs) | Fungal Infection | 3.3 percentage of participants |
Secondary
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
Secondary
Post Vaccination SIIL 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
Secondary
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
Secondary
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