Safety of LAIV4 in Children With Asthma

The study will be conducted at three sites: Vanderbilt University Medical Center (Lead site),
Cincinnati Children's Hospital Medical Center (contributing site), and Duke University
Medical Center (contributing site) during the 2018-2019 influenza season. Participants will
be randomized 1:1 to receive either a single intranasal dose of licensed quadrivalent LAIV
(LAIV4) or an intramuscular injection of quadrivalent IIV4 (IIV4), stratifying by asthma
severity (mild vs. moderate-to-severe). Vanderbilt will enroll about 100 participants,
Cincinnati will enroll about 110 participants, and Duke will enroll about 90 participants.
After enrollment, participants will be followed for 43 days via 5 additional phone, email, or
text visits to monitor systemic reactogenicity, asthma symptoms and exacerbations, and
serious adverse events. The primary objective is to compare proportions of participants with
asthma exacerbations during the 42 days after LAIV4 versus IIV4. Because of the potential for
increased risk of wheezing after LAIV, the use of LAIV in persons with asthma has been an
area of vaccine safety research for many years; the safety issue remains unresolved. A
clinical study to assess the safety of LAIV4 in children with asthma could expand the
evidence base and inform clinical decision-making and public health policy.

Inclusion Criteria:

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

- Participant must have a current diagnosis of persistent asthma (Physician diagnosis of
asthma and current prescribed use of a long-acting controller medication. For purposes
of this study, we have considered "controller" medications to be any single or
combination use of long-acting medications used to prevent asthma exacerbations and to
achieve long-term control of asthma (as compared to short-acting rescue medication).)

- Parent(s) or legal guardian(s) must provide written, informed consent and participant
must provide assent as appropriate for age prior to initiation of study procedures and
according to local IRB requirements

- Parent(s) or legal guardian(s) and participant must be willing and able to comply with
planned study procedures and be available for all study visits

- Is in good health, other than their asthma, as determined by medical history

- English or Spanish literate (only English-speaking participants will be included at
the Cincinnati and Duke sites)

- Intention of being available for entire study period and complete all relevant study
procedures, including follow-up using at least one of the following methods: phone
calls, text messages, or emails

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
(this may result in a temporary delay of vaccination)

- History of a severe allergic reaction (e.g., anaphylaxis) after a previous dose of any
influenza vaccine or after any component of the influenza vaccine, including egg
protein.

- 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 (2018-2019 influenza season) licensed influenza vaccine for
children 9-11 years (only). (Clarification: Children aged 5-8 years are permitted to
be enrolled if they have received zero or one dose of the 2018-2019 influenza season
vaccine, and require two doses of the 2018-2019 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

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

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

- Have known 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)

- Received influenza antiviral medication within 48 hours prior to study vaccination

- History of Guillian-Barré syndrome within 6 weeks of previous influenza vaccination

- Have 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 a positive urine or serum pregnancy test within 24 hours prior to vaccination in a
post-menarchal female. LAIV is not recommended for use in pregnant females.

- Currently taking aspirin or aspirin-containing products

- Any parent(s) or legal guardian(s) who is an immediate relative of study staff or is
an employee supervised by study staff.