Influenza
Conditions
Keywords
influenza vaccine, trivalent live-attenuated influenza vaccine, efficacy, Africa, Senegal
Brief summary
This study will provide the Senegal Ministry of Health with data on the clinical efficacy of the Live-Attenuated Influenza Vaccine (LAIV). This data will inform future policy considerations for influenza vaccine.
Detailed description
This study is a double-blind, individual-randomized, placebo-controlled, clinical efficacy trial among healthy children aged 24 through 71 months in the Niakhar area of Senegal. A total of 1,761 healthy children will be randomized in a 2:1 ratio of LAIV to placebo. For evaluation of efficacy, passive and active surveillance will be conducted weekly throughout the study to identify outcomes among vaccinated subjects. Children meeting the protocol-defined clinical case definition will have a nasal swab and throat swab specimen collected for testing by rRT-PCR for evidence of influenza virus infection. 100 of the 1,761 participants were also included in a substudy designed to evaluate virologic evidence of LAIV replication. As such, nasal and throat swab specimens were collected on day 0 (prior to vaccination), as well as on post-vaccination days 2, and 4 from all subjects included in the substudy. These specimens will be tested for presence of wild-type and vaccine virus. Additionally, a more detailed assessment of vaccine reactogenicity will be made among these children by actively collecting solicited and unsolicited reactions at each study visit for the week post vaccination (days 2 and 4).
Interventions
BIOLOGICALSIIL Live Attenuated Influenza Vaccine
Trivalent live-attenuated influenza vaccine 2012/2013 Northern Hemisphere vaccine containing A/California/7/2009 (H1N1), A/Victoria/361/2011 (H3N2), B/Wisconsin/1/2010
BIOLOGICALMatched placebo
Matched placebo will be identical to reconstituted SIIL LAIV in ingredients and concentrations except A/California/7/2009 (H1N1), A/Victoria/361/2011 (H3N2), B/Wisconsin/1/2010 will be replaced with egg allantoic fluid.
Sponsors
Institut de Recherche pour le Developpement
Institut Pasteur de Dakar
Centers for Disease Control and Prevention
PATH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
24 Months to 71 Months
Healthy volunteers
Yes
Inclusion criteria
* Healthy male or female child at least 24 months of age and no older than 71 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 Niakhar DSS 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
* Serious, active, medical condition, including: chronic disease of any body system,chronic infections such as tuberculosis, genetic disorders, such as Down's syndrome or other cytogenetic disorder, known or suspected disease of the immune system of any kind. * 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. * History of Guillain-Barré syndrome. * Receipt of immunosuppressive agents, including systemic corticosteroids, during the month before planned study vaccination. * Receipt of aspirin therapy or aspirin-containing therapy within the two weeks before planned study vaccination. * History of any severe allergic reaction with generalized urticarial, angioedema, or anaphylaxis. * Receipt of an influenza vaccine within the past 12 months. * 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 or make it unlikely that the child would complete the study. Temporary Contraindications: * Acute illness accompanied by a body temperature of 37.5°C or above (axillary measurement) within 14 days of enrollment visit. * Any acute respiratory infection within 14 days of enrollment visit. * Any illness accompanied by active wheezing within 14 days of enrollment visit.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants With Symptomatic, Laboratory-confirmed Influenza Virus Infection (Regardless of Vaccine Match) | Through 7 to 8 months post vaccination |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety Profile of LAIV: Immediate Reactions Occurring Within 30 Minutes of Administration of Study Vaccine. | Through 30 minutes post vaccination | — |
| Safety Profile of LAIV: Solicited and Unsolicited Local and Systemic Reactions | Through 7 days post vaccination | — |
| Safety Profile of LAIV: Serious Adverse Events | Through 1 month post vaccination | — |
| Safety Profile of LAIV: Other Non-serious Adverse Events | Through 1 month post vaccination | — |
| Evaluation of Vaccine-take as Shedding of Vaccine Virus Post-vaccination, Including Viral Load and Duration of Virus Detection | Through 4 days post vaccination | Vaccine take will be parameterized as the percentage of participants with detectable vaccine-virus in nasal or throat swab on each day pre- (day 0) and post vaccination (i.e., 2 and 4 days post vaccination), and the quantity of detected virus. |
| Percentage of Participants With Symptomatic, Laboratory-confirmed Influenza Virus Infection (Vaccine-matched Strains) | Through 7 to 8 months post vaccination | — |
| Percentage of Participants With Symptomatic, Laboratory-confirmed Influenza Virus Infection by Influenza Type/Subtype (Influenza A/H1N1, Influenza A/H3N2, and Influenza B) | Through 7 to 8 months post vaccination | — |
| Clinical Characteristics of Influenza in the Study Population | Through 7 to 8 months post vaccination | — |
| Etiologies of Influenza-like Illness in the Study Population | Through 7 to 8 months post vaccination | Bacterial and viral etiologies of acute respiratory and febrile illness will be parameterized as the percentage of those with each particular laboratory-confirmed infection categorized by vaccine allocation. |
| Safety Profile of LAIV: Protocol Defined Wheezing Illness | Through 7 to 8 months post vaccination | — |
Countries
Senegal
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vaccine Single dose of trivalent live-attenuated influenza vaccine 2012/2013 Northern Hemisphere vaccine containing A/California/7/2009 (H1N1), A/Victoria/361/2011 (H3N2), B/Wisconsin/1/2010 | 1,174 |
| Placebo Single dose of placebo will be identical to reconstituted SIIL LAIV in ingredients and concentrations except A/California/7/2009 (H1N1), A/Victoria/361/2011 (H3N2), B/Wisconsin/1/2010 will be replaced with egg allantoic fluid. | 587 |
| Total | 1,761 |
Baseline characteristics
| Characteristic | Vaccine | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1174 Participants | 587 Participants | 1761 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 Senegal | 1174 participants | 587 participants | 1761 participants |
| Sex: Female, Male Female | 564 Participants | 290 Participants | 854 Participants |
| Sex: Female, Male Male | 610 Participants | 297 Participants | 907 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 56 / 1,174 | 33 / 587 |
| serious Total, serious adverse events | 7 / 1,174 | 7 / 587 |
Outcome results
Primary
Percentage of Participants With Symptomatic, Laboratory-confirmed Influenza Virus Infection (Regardless of Vaccine Match)
Time frame: Through 7 to 8 months post vaccination
Population: All participants meeting per-protocol analysis criteria.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vaccine | Percentage of Participants With Symptomatic, Laboratory-confirmed Influenza Virus Infection (Regardless of Vaccine Match) | 17.9 percentage of participants |
| Placebo | Percentage of Participants With Symptomatic, Laboratory-confirmed Influenza Virus Infection (Regardless of Vaccine Match) | 18.0 percentage of participants |
p-value: 0.996Log Rank
Secondary
Clinical Characteristics of Influenza in the Study Population
Time frame: Through 7 to 8 months post vaccination
Secondary
Etiologies of Influenza-like Illness in the Study Population
Bacterial and viral etiologies of acute respiratory and febrile illness will be parameterized as the percentage of those with each particular laboratory-confirmed infection categorized by vaccine allocation.
Time frame: Through 7 to 8 months post vaccination
Secondary
Evaluation of Vaccine-take as Shedding of Vaccine Virus Post-vaccination, Including Viral Load and Duration of Virus Detection
Vaccine take will be parameterized as the percentage of participants with detectable vaccine-virus in nasal or throat swab on each day pre- (day 0) and post vaccination (i.e., 2 and 4 days post vaccination), and the quantity of detected virus.
Time frame: Through 4 days post vaccination
Secondary
Percentage of Participants With Symptomatic, Laboratory-confirmed Influenza Virus Infection by Influenza Type/Subtype (Influenza A/H1N1, Influenza A/H3N2, and Influenza B)
Time frame: Through 7 to 8 months post vaccination
Secondary
Percentage of Participants With Symptomatic, Laboratory-confirmed Influenza Virus Infection (Vaccine-matched Strains)
Time frame: Through 7 to 8 months post vaccination
Secondary
Safety Profile of LAIV: Immediate Reactions Occurring Within 30 Minutes of Administration of Study Vaccine.
Time frame: Through 30 minutes post vaccination
Secondary
Safety Profile of LAIV: Other Non-serious Adverse Events
Time frame: Through 1 month post vaccination
Secondary
Safety Profile of LAIV: Protocol Defined Wheezing Illness
Time frame: Through 7 to 8 months post vaccination
Secondary
Safety Profile of LAIV: Serious Adverse Events
Time frame: Through 1 month post vaccination
Secondary
Safety Profile of LAIV: Solicited and Unsolicited Local and Systemic Reactions
Time frame: Through 7 days post vaccination