Clinical trial NCT01854632: Clinical Efficacy of Trivalent Live-Attenuated Influenza Vaccine (LAIV) Among Children in Senegal
Official title: A Randomized, Double-Blind, Placebo-Controlled Trial of the Clinical Efficacy of Trivalent Live-Attenuated Influenza Vaccine (LAIV) Among Children in Senegal
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Influenza
Keywords: influenza vaccine
trivalent live-attenuated influenza vaccine
efficacy
Africa
Senegal
Lead sponsor: PATH
Sponsor class: OTHER
Collaborators: name: Institut de Recherche pour le Developpement
name: Institut Pasteur de Dakar
name: Centers for Disease Control and Prevention
First posted: 2013-05-15
Enrollment: 1761
Sex: ALL
Minimum age (years): 24
Maximum age (years): 71
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Symptomatic, Laboratory-confirmed Influenza Virus Infection (Regardless of Vaccine Match)
timeFrame: Through 7 to 8 months post vaccination
Secondary outcomes:
measure: Safety Profile of LAIV: Immediate Reactions Occurring Within 30 Minutes of Administration of Study Vaccine.
timeFrame: Through 30 minutes post vaccination
measure: Safety Profile of LAIV: Solicited and Unsolicited Local and Systemic Reactions
timeFrame: Through 7 days post vaccination
measure: Safety Profile of LAIV: Serious Adverse Events
timeFrame: Through 1 month post vaccination
measure: Safety Profile of LAIV: Other Non-serious Adverse Events
timeFrame: Through 1 month post vaccination
measure: Safety Profile of LAIV: Protocol Defined Wheezing Illness
timeFrame: Through 7 to 8 months post vaccination
measure: Percentage of Participants With Symptomatic, Laboratory-confirmed Influenza Virus Infection (Vaccine-matched Strains)
timeFrame: Through 7 to 8 months post vaccination
measure: Percentage of Participants With Symptomatic, Laboratory-confirmed Influenza Virus Infection by Influenza Type/Subtype (Influenza A/H1N1, Influenza A/H3N2, and Influenza B)
timeFrame: Through 7 to 8 months post vaccination
measure: Clinical Characteristics of Influenza in the Study Population
timeFrame: Through 7 to 8 months post vaccination
measure: Etiologies of Influenza-like Illness in the Study Population
timeFrame: Through 7 to 8 months post vaccination
measure: Evaluation of Vaccine-take as Shedding of Vaccine Virus Post-vaccination, Including Viral Load and Duration of Virus Detection
timeFrame: Through 4 days post vaccination
Other outcomes:
Locations:
city: Niakhar
country: Senegal
facility: Institut de Recherche pour le Développement (IRD), Niakhar station
Study officials:
affiliation: Institut de Recherche pour le Développement (IRD)
name: Aldiouma Diallo, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Victor JC, Lewis KD, Diallo A, Niang MN, Diarra B, Dia N, Ortiz JR, Widdowson MA, Feser J, Hoagland R, Emery SL, Lafond KE, Neuzil KM. Efficacy of a Russian-backbone live attenuated influenza vaccine among children in Senegal: a randomised, double-blind, placebo-controlled trial. Lancet Glob Health. 2016 Dec;4(12):e955-e965. doi: 10.1016/S2214-109X(16)30201-7. Epub 2016 Oct 13.