Cockroach Immunotherapy in Children and Adolescents

This is a 1:1 randomized, double-masked (blind), placebo-controlled, multicenter trial with 2
treatment arms:

- German Cockroach Subcutaneous Immunotherapy (SCIT) + guideline-based standard asthma
care, OR

- Placebo (for German Cockroach Subcutaneous Immunotherapy [SCIT]) + guideline-based
standard asthma care

The study will occur in two parts - Part A and Part B:

- Part A will enroll 80 participants 8 to 14 years of age, who are sensitized to cockroach,
have asthma, and a positive cockroach Nasal Allergen Challenge (NAC) before treatment
randomization.

An interim analysis will be conducted when all Part A participants have completed their
12-month NAC. If an effect is seen for the Part A NAC analysis, the study will proceed to
Part B.

-Part B will enroll 220 participants 6 to 16 years of age, who are sensitized to cockroach
and have asthma. A positive NAC will not be required for inclusion into Part B.

The study will be based on a continuous treatment schedule with German cockroach allergenic
extract or placebo, up to a maximum of 36 months.

Inclusion Criteria:Participant(s)

- And/or parent guardian must be able to understand and provide informed consent;

- Age at date of recruitment (e.g., screening):

- in Part A: 8 to 14 years of age

- in Part B: 6 to 16 years of age

- Must have a primary place of residence in one of the pre-selected recruitment census
tracts (Reference: Inner-City Asthma Consortium);

- Has a history of persistent asthma, for a minimum of 1 year before study entry:

- Diagnosis of asthma will be defined as a report by the caretaker that the
participant had a clinical diagnosis of asthma made by a clinician ≥1 year ago,
resulting in a prescription of preventative asthma medication, and

- Must have persistent asthma as defined by the current need for at least 88 mcg
fluticasone (or the equivalent of another inhaled corticosteroid) to control
asthma at the time of screening.

- At the time of randomization, the participant's asthma must be well controlled as
defined by:

- A Forced Expiratory Volume in 1 second (FEV1) ≥80% predicted, and

- An Asthma Control Test (ACT) or Childhood Asthma Control Test (CACT) score ≥20.

- Is sensitive to German cockroach as documented by:

- a positive (≥3 mm greater than negative control) skin prick test result, and

- detectable German cockroach specific Immunoglobulin E (IgE) (≥ 0.35 kUA/L).

- Has no known contraindications to therapy with glycerinated German cockroach
allergenic extract or placebo;

- In Part A only: participant must have a positive cockroach nasal challenge, as defined
by reaching a Total Nasal Symptom Score (TNSS) of ≥6 or a sneezing score of 3 at dose
2 or above during the challenge at screening; and

- Have documentation of current medical insurance with prescription coverage at
randomization.

Exclusion Criteria:Participant(s)

- Unable or unwilling to give written informed consent or comply with the study
protocol;

- That is pregnant or lactating;

- That are post-menarcheal females must be abstinent or use a medically acceptable birth
control method throughout their participation in the study (e.g. oral, subcutaneous,
mechanical, or surgical contraception);

- That cannot perform spirometry and peak flow at treatment randomization;

- That have an asthma severity classification at the time of treatment randomization of
severe persistent, using the The National Asthma Education and Prevention Program
(NAEPP) classification, as evidenced by at least one of the following:

- Requires a dose >500 mcg of fluticasone per day or the equivalent of another
inhaled corticosteroid,

- Has received more than 2 courses of oral or parenteral corticosteroids in the
last 12 months or one course within the last 3 months prior to study entry,

- Has been treated with depot steroids within the 3 months prior to study entry,

- Has been hospitalized for asthma within the 6 months prior to study entry, or

- Has had a life-threatening asthma exacerbation that required intubation,
mechanical ventilation, or that resulted in a hypoxic seizure within 2 years
prior to study entry.

- Does not have access to a phone (needed for scheduling appointments);

- Has received allergen immunotherapy (Sublingual Immunotherapy [SLIT] or Subcutaneous
Immunotherapy [SCIT]) in the last 12 months or, who plan to initiate or resume
allergen immunotherapy during the study;

- Has received biologic therapy (e.g., anti-Immunoglobulin E [IgE], anti-IL-4,
anti-IL-5) within 6 months of study entry;

- Has received an investigational drug in the 30 days prior to recruitment or who plan
to use an investigational drug during the study;

- Has past or current medical problems or findings from physical examination or
laboratory testing that are not listed above, which, in the opinion of the
investigator, may:

- pose additional risks from participation in the 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.

- Who have nasal polyps or other major structural abnormalities in their nasal cavities
as assessed by anterior rhinoscopy,

- Who meet any of the following criteria are not eligible for enrollment and may not be
reassessed:

- That plan to move from the area during the study period,

- Have a history of anaphylaxis grade 3 or higher as defined by World Allergy
Organization Subcutaneous Immunotherapy Systemic Reaction Grading System,

- Have unstable angina, significant arrhythmia, uncontrolled hypertension, history
of autoimmune disease, or other chronic or immunological diseases that, in the
opinion of the investigator, might interfere with the evaluation of the
investigational product or pose additional risk to the participant,

- Past or current medical problems or findings from physical examination or
laboratory testing that are not listed above, which, in the opinion of the
investigator,

- may pose additional risks from participation in the 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.

- Are using tricyclic antidepressants or beta-adrenergic blocker drugs (both oral
and topical).