A Trial of Mepolizumab Adjunctive Therapy for the Prevention of Asthma Exacerbations in Urban Children

Asthma is a growing problem, especially in children. It causes frequent wheezing, shortness
of breath, chest tightness, and cough. Asthma attacks, or exacerbations, are problems for
children with asthma.

The purpose of this study is to see if treatment with a medication called Nucala®
(mepolizumab), given along with standard asthma care, makes children less likely to have
asthma attacks. Mepolizumab is a new drug that is approved by the Food and Drug
Administration (FDA) for use in children with asthma who are aged 12 years and older.
Mepolizumab is given by injection. It is being studied by other researchers in children aged
6-11 years.

All participants will be prescribed standard asthma medications by a clinician who is trained
in asthma care. Medications will include controller medications, a rescue medication, and a
medication for severe asthma attacks (prednisone). The amount of medication that participants
receive may be increased or decreased during the study based on their symptoms and breathing
test results. Study clinicians will treat all participants according to the same guidelines.
These treatment guidelines are based on recommendations from a group of national experts in
asthma. This study has been designed this way so that all participants will have safe and
effective standard asthma care.

In order to enroll in this study, participants must be willing to have their asthma managed
by the study clinician during the entire study period. Participants must also be willing to
bring study medications to all study visits.

This study will include up to 20 study visits. Participant involvement in the study will
endure for approximately 1 year.

During the treatment period, participants will be placed in one of two treatment groups:

- Mepolizumab injection and guidelines-based asthma care or

- Placebo injection and guidelines-based asthma care.

Participants will not be able to choose which group they are assigned. This assignment is
random and by chance, much like flipping a coin. Participants will not know if they are
receiving mepolizumab or placebo. Investigators will compare the study results between the
participants of each group.

Inclusion Criteria:

- Participant and/or parent guardian must be able to understand and provide informed
consent and age-appropriate assent;

- Participant must have a primary place of residence in one of the pre-selected
recruitment census tracts as outlined in the Protocol ICAC-30 Manual of Procedures
(MOP);

- Participant has had a diagnosis of asthma made >1 year prior to recruitment;

--participants who received an asthma diagnosis by a clinician ≤ year prior to
recruitment must report that their respiratory symptoms were present for more than 1
year prior to recruitment.

- Participant has had ≥2 asthma exacerbations in the prior year (defined as a
requirement for systemic corticosteroids and/or hospitalization);

- At Visit 0 (Screening), have the following requirement for asthma controller
medication:

- for participants aged 6 to 11 years, treatments with at least fluticasone 250 mcg
dry powder inhaler (DPI) one puff twice daily or its equivalent and,

- for participants aged 12 years and older, treatment with at least Advair 250/50
mcg DPI one puff twice daily or its equivalent.

- Have peripheral blood eosinophils ≥150 cells/µl obtained at Visit 0 (Screening) or via
another Inner-City Asthma Consortium (ICAC) clinical research study within 6 months;

- Is able to perform spirometry at randomization (Visit for treatment assignment);.

- Has documentation of current medical insurance with prescription coverage at
randomization; and

- Has had varicella or the varicella vaccination.

Exclusion Criteria:

- Are not able or willing to give written informed consent or comply with study
protocol;

- Has concurrent (existing) medical problems that would require systemic corticosteroids
or other immunomodulator treatments during the study;

- Is currently receiving immunotherapy;

- Is currently receiving treatment with omalizumab or has had omalizumab treatment
within 6 months prior to planned participant randomization to treatment assignment;

- Is currently pregnant or lactating, or plans to become pregnant during the time of
study participation

--Females of child-bearing potential (post-menarche) must be abstinent or use a
medically acceptable birth control method throughout the study (e.g. oral
subcutaneous, mechanical, or surgical contraception);

- Has a known, pre-existing clinically important lung condition other than asthma;

- Has a current malignancy or previous history of cancer in remission for less than 12
months prior to randomization;

- Has known, pre-existing, unstable liver disease;

- Is a current smoker or has a smoking history of 10 or more pack years;

- Has a known immunodeficiency disease;

- Has other conditions that could lead to elevated eosinophils such as hypereosinophilic
syndromes, including eosinophilic granulomatosis with polyangiitis;

- Has a known, pre-existing parasitic infestation within 6 months of randomization:

- Use of investigational drugs within 4 weeks of randomization:

- Has a past or current medical problems or findings from physical examination or
laboratory testing that are not listed above, which, in the opinion of the study
clinician, may pose additional risks from participation in this study, may interfere
with the participant's ability to comply with study requirements, or that may impact
the quality or interpretation of the data obtained from the study;

- In the event that the participant will not allow the study clinician, an asthma
specialist, to manage their disease for the duration of the study or who are not
willing to change their asthma medications to follow the protocol;

- Has a known history of allergic reaction to previous biologic therapy for asthma; or

- Has had a life threatening asthma exacerbation in the last 2 years requiring
intubation, mechanical ventilation or resulting in a hypoxic seizure.