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A Trial of Mepolizumab Adjunctive Therapy for the Prevention of Asthma Exacerbations in Urban Children (MUPPITS-2)

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ClinicalTrials.gov Identifier: NCT03292588
Recruitment Status : Recruiting
First Posted : September 25, 2017
Last Update Posted : January 18, 2020
Sponsor:
Collaborators:
Inner-City Asthma Consortium
GlaxoSmithKline
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE September 20, 2017
First Posted Date  ICMJE September 25, 2017
Last Update Posted Date January 18, 2020
Actual Study Start Date  ICMJE November 7, 2017
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 20, 2017)
Number of asthma exacerbations [ Time Frame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment) ]
Asthma exacerbation defined as a prescribed course of systemic steroids by a clinician or initiation of a course of systemic steroids by a participant or a hospitalization for asthma. If a participant initiates and completes a course of systemic steroids without clinician involvement, this course will be counted only if it meets the following minimum dosage: prednisone, prednisolone, or methylprednisolone at ≥ 20mg per day for 3 of any 5 consecutive days; or dexamethasone at ≥10mg per day for ≥1 day.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 20, 2017)
  • Composite Asthma Severity Index (CASI) [ Time Frame: Visits (V) 1 (Week 4 Treatment Initiation) , V4 (Week 16), V7 (Week 28), V10 (Week 40), V13 (Week 52) and V14 (Week 56, Completion of Treatment) ]
    CASI scores include 5 domains: day symptoms and albuterol use, night symptoms and albuterol use, controller treatment, lung function measures, and exacerbations. To calculate CASI, the 5 domain scores are summed to determine a final score, which can range from 0 to 20, with 0 being no severity of asthma and 20 being extremely severe asthma.
  • Participant Quality of Life Measured Using the Physician-Patient Global Assessment Tool [ Time Frame: Visit 14 (Week 56, Completion of Treatment) ]
    A validated rating scale in which a participant rates their response to therapy.
  • Pulmonary Function Measured by Spirometry: Forced Expiratory Volume in 1 Second (FEV1) % Predicted [ Time Frame: Visits (V) 1 (Week 4 Treatment Initiation) , V4 (Week 16), V7 (Week 28), V10 (Week 40), V13 (Week 52) and V14 (Week 56, Completion of Treatment) ]
    FEV1 is air volume exhaled in 1 second during spirometry. Asthma severity classification for trial: mild--pre-bronchodilator FEV1 ≥ 80% predicted requiring no/ low-moderate dose of inhaled glucocorticoids; moderate--pre-bronchodilator FEV1 <80% predicted requiring no/ low-moderate dose of inhaled glucocorticoids; severe--requiring high-dose inhaled glucocorticoids with/without continuous/near continuous oral glucocorticoids, or uncontrolled despite treatment. FEV1 percent of predicted value is FEV1 converted to a percentage of normal, based on height, weight, and race. This measurement will be performed by trained and certified clinical research staff according to American Thoracic Society standards as performed routinely in usual care as part of subspecialist management of asthma.
  • Pulmonary Function Measured by Impulse Oscillometry (IOS) [ Time Frame: Visits (V) 1 (Week 4 Treatment Initiation) , V4 (Week 16), and V13 (Week 52) ]
    A pulmonary measure of airway resistance and reactance. This measurement will be performed by trained and certified clinical research staff according to American Thoracic Society standards as performed routinely in usual care as part of subspecialist management of asthma.
  • Time to First Asthma Exacerbation [ Time Frame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment) ]
    Time between initiation of treatment and first asthma exacerbation or the end of participant follow-up visits.
  • Number of Reported Adverse Events (AEs), Including Their Severity and Treatment Relatedness [ Time Frame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment) ]
    The number of AEs by severity and relationship to study drug will be used to assess safety.
  • Number of Reported Serious Adverse Events (SAEs) Inclusive of Severity and Treatment Relatedness [ Time Frame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment) ]
    The number of SAEs by severity and relationship to study drug will be used to assess safety.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: September 20, 2017)
  • EXPLORATORY: Time to First Respiratory Virus-Induced Exacerbation [ Time Frame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment) ]
    As measured by an exacerbation associated with a respiratory virus detected using nasal mucus samples obtained at the time of an exacerbation.
  • EXPLORATORY:Number of Respiratory Virus-Induced Exacerbations [ Time Frame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment) ]
    Measured by an exacerbation associated with a respiratory virus detected using nasal mucus samples obtained at the time of an exacerbation.
  • EXPLORATORY:Childhood Asthma Control Test (ACT)/c-ACT [ Time Frame: Visits (V) 4 (Week 4 Treatment Initiation) , V4 (Week 16), V7 (Week 28), V10 (Week 40), V13 (Week 52) and V14 (Week 56, Completion of Treatment) ]
    A validated tool to assess overall asthma control (over the last 4 weeks) in participants.
  • EXPLORATORY:Maximum Number of Asthma Symptom Days [ Time Frame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment) ]
    Defined as the highest value among the following variables over a two-week period:
    • number of days with wheezing, tightness in the chest, or cough;
    • number of nights with disturbed sleep as a result of asthma; and
    • number of days on which the participant had to slow down or discontinue play/physical activities.
  • EXPLORATORY:Bronchodilator Responsiveness [ Time Frame: Baseline (prior to treatment initiation), Week 56 (Completion of Treatment) ]
    A measure to determine whether mepolizumab improves pulmonary outcomes.
  • EXPLORATORY: Gene Expression in Nasal Lavage Samples [ Time Frame: Visits (V) 1 (Week 4 Treatment Initiation) , V3(Week 12), and V14 (Week 56, Completion of Treatment) ]
    Whole genome transcriptomics of nasal lavage samples to identify inflammatory pathways affected by mepolizumab.
  • EXPLORATORY: Gene Expression in Whole Blood RNA Samples [ Time Frame: Visits (V) 1 (Week 4 Treatment Initiation) , V3(Week 12), and V14 (Week 56, Completion of Treatment) ]
    Whole genome transcriptomics of whole blood RNA samples to identify inflammatory pathways affected by mepolizumab..
  • EXPLORATORY:Levels of Antibody to Mepolizumab [ Time Frame: Visit (V) 1 (Week 4, prior to treatment initiation), V3 (Week 12), and Visit 14 (Week 56, Completion of Treatment) ]
    An assay for detection/measurement of levels of antibody to mepolizumab. Analysis will include participants randomized to mepolizumab.
  • EXPLORATORY:Other Potential Biomarkers Not Specified to Date [ Time Frame: Visit (V) 1 (Week 4, prior to treatment initiation), V3 (Week 12), and Visit 14 (Week 56, Completion of Treatment) ]
    Plasma, nasal samples, RNA and DNA will be banked for possible future study of potential biomarkers associated with asthma and asthma exacerbations.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE A Trial of Mepolizumab Adjunctive Therapy for the Prevention of Asthma Exacerbations in Urban Children
Official Title  ICMJE Mechanisms Underlying Asthma Exacerbations Prevented and Persistent With Immune-Based Therapy: A Systems Approach Phase 2 (ICAC-30)
Brief 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.
Detailed Description

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 mepolizumab (Nucala®), 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Asthma
Intervention  ICMJE
  • Biological: Mepolizumab

    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.

    Other Names:
    • Nucala®
    • anti-Interleukin 5 (IL5) antagonist monoclonal antibody
  • Drug: Placebo

    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.

    Other Name: Placebo for Mepolizumab
Study Arms  ICMJE
  • Experimental: Mepolizumab
    Intervention: Mepolizumab plus guidelines-based standard of care asthma treatment.
    Intervention: Biological: Mepolizumab
  • Placebo Comparator: Placebo
    Intervention: Placebo for mepolizumab plus guidelines-based standard of care asthma treatment.
    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 20, 2017)
320
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2021
Estimated Primary Completion Date March 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03292588
Other Study ID Numbers  ICMJE DAIT ICAC-30
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE
  • Inner-City Asthma Consortium
  • GlaxoSmithKline
Investigators  ICMJE
Study Chair: Daniel J Jackson, MD University of Wisconsin, Madison
Study Chair: William W Busse, MD University of Wisconsin, Madison
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP