Influenza Vaccine Feasibility Study in Children With Persistent Asthma

The association of an increased risk in wheezing following receipt of a live-attenuated
influenza vaccine in children at least 2 years of age with a prior history of asthma or
wheeze remains unclear.

The Centers for Disease Control (CDC) and Prevention's Clinical Immunization Safety
Assessment (CISA) planned to address a data safety gap regarding use of LAIV4 vaccine in
children with asthma by conducting a 3-site randomized, non-inferiority prospective study.
The main goal was to compare the safety of LAIV4 versus IIV4 in children 5-11 years with
persistent asthma during the 2016-2017 influenza season. CDC and the CISA study sites
developed a protocol and associated materials, and were poised to begin enrollment early
during the 2016-2017 influenza season. However, after the June 22, 2016 Advisory Committee on
Immunization Practices (ACIP) vote recommending against use of LAIV4 during the 2016-2017
influenza season, CDC and study investigators decided to defer implementing a study using
LAIV4 during the 2016-2017 influenza season. Investigators will reconsider initiating this
study during the 2017-2018 influenza season if ACIP votes to reinstate LAIV4 use or new data
become available; ACIP makes recommendations annually.

The planned LAIV4 study had unique features in its design that previously had not been
implemented in vaccine safety studies, including: 1) enrolling a substantial proportion of
children with moderate-severe asthma 2) using digital peak flow meters and 3) collecting
clinical data through multiple, complementary, measures for 42 days after vaccination. To
capitalize on progress made during development of the study protocol and associated documents
and procedures, CISA is proposing to carry out a study at the three sites to assess the
feasibility of recruiting, enrolling, retaining, and collecting clinical data on children
5-11 years with persistent asthma of varied levels of severity in an influenza vaccine safety
study. Findings from this proposed feasibility study will facilitate improving the LAIV4
study in the future if it goes forward through the CISA Project or in another venue. In
2016-2017 season, FDA approved a new influenza vaccine for use in persons aged 4 years and
older, Flucelvax® Quadrivalent (ccIIV4); ACIP incorporated this vaccine into its
recommendations for the 2016-2017 influenza season. Therefore ccIIV4 will be used in place of
LAIV4 for this feasibility study. There is no evidence that Flucelvax® increases the risk of
wheezing in asthmatic children. The feasibility study also offers an opportunity to gain some
additional descriptive safety data for this new vaccine in asthmatic children.

Inclusion Criteria:

- Children between 5-11 years of age, inclusive, at enrollment.

- Participant must have a current diagnosis of persistent asthma.

- Parent/legal guardian must provide written informed consent and subject must provide
assent as appropriate for age prior to initiation of study procedures and according to
local Institutional Review Board (IRB) requirement.

- Parent/legal guardian and subject must be willing and able to comply with planned
study procedures and be available for all study visits.

- Children aged 5-8 years must have received at least 2 doses of seasonal trivalent or
quadrivalent influenza vaccine prior to the current influenza season. Children 9-11
years must have received at least 1 dose of seasonal trivalent or quadrivalent
influenza vaccine prior to the current influenza season.

- Is in good health, other than their asthma, as determined by medical history and
targeted physical examination based on medical history.

- English or Spanish literate.

- Intention of being available for entire study period and complete all relevant study
procedures, including follow-up phone calls and collection of information.

Exclusion Criteria:

- Acute illness and/or a reported oral temperature of ≥ 100.4°F within 72 hours prior to
enrollment (this may result in a temporary delay of vaccination.

- Use of antipyretic medication during the preceding 24 hours that might mask a fever
(temporary deferral).

- History of a severe allergic reaction (e.g., anaphylaxis) to any component of study
influenza vaccines or a known allergy to eggs.

- Receipt of any licensed vaccine within 14 days (for inactivated vaccines) or 28 days
(for live vaccines) prior to vaccination or planned receipt of any licensed vaccine
within 42 days after vaccination.

- Receipt of current year's licensed influenza vaccine.

- Received an investigational agent (licensed or unlicensed vaccine, drug, biologic,
device, blood product, or medication) in the 28 days prior to enrollment or planned
receipt before 42 days after vaccination.

- Has immunosuppression as a result of an underlying illness or treatment, or use of
anticancer chemotherapy or radiation therapy within the preceding 36 months.

- Has taken ≥ 20mg/day of prednisone or its equivalent, for 14 days or more within the
past 28 days.

- Has know active neoplasm or a history of any hematologic malignancy.

- Has had a previous exacerbation of their asthma symptoms requiring systemic steroids
within the prior 28 days, or has had a life-threatening exacerbation of asthma in the
past two years (e.g. hypoxic seizure, mechanical ventilation).

- History of Guillian-Barre syndrome within 6 weeks of previous influenza vaccination.

- Has any condition that, in the opinion of the investigator, would interfere with the
evaluation of the responses or would place the participant at unacceptable risk of
injury.

- Has any diagnosis, current or past, of schizophrenia, bipolar disease, or other major
psychiatric disorder.

- Currently taking aspirin or aspirin-containing products.