A Trial of Mepolizumab Adjunctive Therapy for the Prevention of Asthma Exacerbations in Urban Children
Condition: Asthma
MeSH terms: Asthma
Intervention: Mepolizumab; Placebo
Intervention description: Mepolizumab administered every 4 weeks by subcutaneous injection at a dose of:
100 mg for participants ≥12 years of age and
40 mg for participants ages 6 to 11 years and weighing ≥40 kg.
Note: Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in the study under previous versions of the protocol and were initially assigned a 100 mg dose will have their dose reduced to 40 mg.
Participants 11 years of age will increase to the 100 mg dose if they become age 12 years during the study.; Placebo administered every 4 weeks by subcutaneous injection at a dose of:
100 mg for participants ≥12 years of age and
40 mg for participants ages 6 to 11 years and weighing ≥40 kg.
Note: Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in the study under previous versions of the protocol and were initially assigned a 100 mg dose will have their dose reduced to 40 mg.
Participants 11 years of age will increase to the 100 mg dose if they become age 12 years during the study.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 335.0
Sex: All
Minimum age: 6 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: urban setting; children and adolescents; double-masked, placebo-controlled randomized trial; asthma exacerbations (attacks); mepolizumab adjunctive therapy; asthma exacerbations prevention; difficult-to-control exacerbation-prone asthma

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

        Study applicant(s) that fulfill all of the inclusion criteria and none of the exclusion
        criteria are eligible for the study-

          -  Participant and/or parent guardian must be able to understand and provide informed
             consent and age-appropriate assent;

          -  Must have a primary place of residence in one of the pre-selected recruitment census
             tracts as outlined in the study's Manual of Procedures (MOP);

          -  Has had a diagnosis of asthma made >1 year prior to recruitment;

             --Those who received an asthma diagnosis by a clinician ≤1 year prior to recruitment
             must report that their respiratory symptoms were present for more than 1 year prior to
             recruitment.

          -  Has had ≥2 asthma exacerbations in the prior year (defined as a requirement for
             systemic corticosteroids and/or hospitalization);

          -  At Visit 0 (Screening), has the following requirement for asthma controller
             medication:

               -  For those ages 6 to 11 years, treatments with at least fluticasone 250 mcg dry
                  powder inhaler (DPI) one puff twice daily or its equivalent and,

               -  For those ≥12 years of age, treatment with at least Advair 250/50 mcg dry powder
                  inhaler (DPI), one puff twice daily or its equivalent.

          -  Has peripheral blood eosinophils ≥150 cells/µl obtained at Visit 0 (Screening) or in
             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:

        Individual(s) who meets any of the following criteria are not eligible for enrollment or
        randomization-

          -  Is not able or willing to give written informed consent or comply with the 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 requiring greater than fluticasone 500 mcg administered twice daily plus
             a long-acting beta agonist (LABA) one puff twice daily or its equivalent, and/or

             --Individuals using oral corticosteroids daily or every other day for more than 14
             days at the time of Visit 0 (Screening).

          -  Is currently pregnant or lactating, or plans to become pregnant during the time of
             study participation

             --Note: 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, active pre-existing parasitic infestation or is undergoing treatment for
             a parasitic infestation

             --Note: Once the individual has been successfully treated, the interested study
             applicant may be reevaluated for study eligibility.

          -  Positive for 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

               -  May impact the quality or interpretation of the data obtained from the study.

          -  In the event that the study applicant 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.