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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 : November 7, 2018
Sponsor:
Collaborators:
Inner-City Asthma Consortium
GlaxoSmithKline
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

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.

Condition or disease Intervention/treatment Phase
Asthma Biological: Mepolizumab Drug: Placebo Phase 2

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 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 320 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Mechanisms Underlying Asthma Exacerbations Prevented and Persistent With Immune-Based Therapy: A Systems Approach Phase 2 (ICAC-30)
Actual Study Start Date : November 7, 2017
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma
Drug Information available for: Mepolizumab

Arm Intervention/treatment
Experimental: Mepolizumab
Intervention: Mepolizumab plus guidelines-based standard of care asthma treatment.
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.
Other Names:
  • Nucala®
  • anti-Interleukin 5 (IL5) antagonist monoclonal antibody

Placebo Comparator: Placebo
Intervention: Placebo for mepolizumab plus guidelines-based standard of care asthma treatment.
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.
Other Name: Placebo for Mepolizumab




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


  4. 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.


  5. 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.

  6. 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.

  7. 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.


Other Outcome Measures:
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. EXPLORATORY:Bronchodilator Responsiveness [ Time Frame: Baseline (prior to treatment initiation), Week 56 (Completion of Treatment) ]
    A measure to determine whether mepolizumab improves pulmonary outcomes.

  6. 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.

  7. 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..

  8. 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.

  9. 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   6 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03292588


Locations
United States, Colorado
Children's Hospital Colorado Not yet recruiting
Aurora, Colorado, United States, 80045
Contact: Pascuala Pinedo-Estrada    720-777-8077    pascuala.pinedo-estrada@childrenscolorado.org   
Principal Investigator: Andrew Liu, MD         
United States, District of Columbia
Children's National Medical Center Recruiting
Washington, District of Columbia, United States, 20010
Contact: Alicia Newcomer    202-476-4698    anewcome@childrensnational.org   
Principal Investigator: Stephen Teach, MD         
United States, Illinois
Ann and Robert Lurie Children's Hospital of Chicago Not yet recruiting
Chicago, Illinois, United States, 60611
Contact: Sarah Godley    312-227-6454    sgodley@luriechildrens.org   
Principal Investigator: Jacqueline Pongracic, MD         
United States, Massachusetts
Boston University School of Medicine Not yet recruiting
Boston, Massachusetts, United States, 02118
Contact: Lisa Gagalis    617-414-3263    lmccay@bu.edu   
Contact: Edlira Gjerasi    (617) 414-3263    edgjeras@bu.edu   
Principal Investigator: George O'Connor, MD         
United States, Michigan
Henry Ford Health System Not yet recruiting
Detroit, Michigan, United States, 48202
Contact: Sherae Hereford    313-916-6954    sherefo3@hfhs.org   
Contact: Debbie Emmer    313 916-6966    demmer1@hfhs.org   
Principal Investigator: Edward Zoratti, MD         
United States, Missouri
St. Louis Children's Hospital Not yet recruiting
Saint Louis, Missouri, United States, 63110
Contact: Beth Tesson    314-286-1290    Tesson_B@kids.wustl.edu   
Principal Investigator: Leonard Bacharier, MD         
United States, New York
Columbia University Medical Center Not yet recruiting
New York, New York, United States, 10032
Contact: Marcela Pierce    212-305-6255    mp2648@cumc.columbia.edu   
Principal Investigator: Meyer Kattan, MD         
United States, Ohio
Cincinnati Children's Hospital Not yet recruiting
Cincinnati, Ohio, United States, 45229
Contact: Kristi Curtsinger    513-803-1651    Kristi.Curtsinger@cchmc.org   
Principal Investigator: Carolyn Kercsmar, MD         
Principal Investigator: Gurjit Hershey, MD         
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Dolores Santoyo    214-648-2620    dolores.santoyo@utsouthwestern.edu   
Principal Investigator: Rebecca Gruchalla, MD         
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Inner-City Asthma Consortium
GlaxoSmithKline
Investigators
Study Chair: Daniel J Jackson, MD University of Wisconsin, Madison
Study Chair: William W Busse, MD University of Wisconsin, Madison

Additional Information:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT03292588     History of Changes
Other Study ID Numbers: DAIT ICAC-30
First Posted: September 25, 2017    Key Record Dates
Last Update Posted: November 7, 2018
Last Verified: November 2018

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

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
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

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases