Clinical trial NCT03292588: A Trial of Mepolizumab Adjunctive Therapy for the Prevention of Asthma Exacerbations in Urban Children
Official title: Mechanisms Underlying Asthma Exacerbations Prevented and Persistent With Immune-Based Therapy: A Systems Approach Phase 2 (ICAC-30)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
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
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Inner-City Asthma Consortium
name: GlaxoSmithKline
name: Rho Federal Systems Division, Inc.
First posted: 2017-09-25
Enrollment: 335
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Number of Asthma Exacerbations During the Treatment Period
timeFrame: Up to 12 months
Secondary outcomes:
measure: Composite Asthma Severity Index (CASI)
timeFrame: Week 12, 24, 36, 48, 52 after randomization
measure: Participant Quality of Life Measured Using the Physician Global Assessment Tool
timeFrame: Week 56
measure: Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14
timeFrame: Week 56
measure: Lung Function as Assessed by Spirometry
timeFrame: Weeks 12, 24, 36, 48, 52 after randomization
measure: Lung Function as Assessed by Impulse Oscillometry
timeFrame: Weeks 12, 24, 36, 48, 52 after randomization
measure: Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Did Not Fit the FDA-approved Dosing Table for Omalizumab Therapy.
timeFrame: Up to 12 months
measure: Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Fit the FDA-approved Dosing Table.
timeFrame: Up to 12 months
measure: Time to First Asthma Exacerbation
timeFrame: Up to 12 months
measure: Number of Reported Adverse Events (AEs), Including Their Severity
timeFrame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)
measure: Number of Reported Adverse Events (AEs), Including Their Treatment Relatedness
timeFrame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)
measure: Number of Reported Serious Adverse Events (SAEs) Inclusive of Severity. Please Refer to the Adverse Event Tables for Specifics.
timeFrame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)
measure: Number of Reported Serious Adverse Events (SAEs) Inclusive of Treatment Relatedness. Please Refer to the Adverse Event Tables for Specifics.
timeFrame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)
Other outcomes:
measure: EXPLORATORY: Time to First Respiratory Virus-Induced Exacerbation
timeFrame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)
measure: EXPLORATORY:Number of Respiratory Virus-Induced Exacerbations
timeFrame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)
measure: EXPLORATORY:Childhood Asthma Control Test (ACT)/c-ACT
timeFrame: 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)
measure: EXPLORATORY:Maximum Number of Asthma Symptom Days
timeFrame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)
measure: EXPLORATORY:Bronchodilator Responsiveness
timeFrame: Baseline (prior to treatment initiation), Week 56 (Completion of Treatment)
measure: EXPLORATORY: Gene Expression in Nasal Lavage Samples
timeFrame: Visits (V) 1 (Week 4 Treatment Initiation) , V3(Week 12), and V14 (Week 56, Completion of Treatment)
measure: EXPLORATORY: Gene Expression in Whole Blood RNA Samples
timeFrame: Visits (V) 1 (Week 4 Treatment Initiation) , V3(Week 12), and V14 (Week 56, Completion of Treatment)
measure: EXPLORATORY:Levels of Antibody to Mepolizumab
timeFrame: Visit (V) 1 (Week 4, prior to treatment initiation), V3 (Week 12), and Visit 14 (Week 56, Completion of Treatment)
measure: EXPLORATORY:Other Potential Biomarkers Not Specified to Date
timeFrame: Visit (V) 1 (Week 4, prior to treatment initiation), V3 (Week 12), and Visit 14 (Week 56, Completion of Treatment)
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Chicago
country: United States
facility: Ann and Robert Lurie Children's Hospital of Chicago
state: Illinois
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
Study officials:
affiliation: University of Wisconsin, Madison
name: Daniel J Jackson, MD
role: STUDY_CHAIR
affiliation: University of Wisconsin, Madison
name: William W Busse, MD
role: STUDY_CHAIR
References:
citation: Jackson DJ, Bacharier LB, Gergen PJ, Gagalis L, Calatroni A, Wellford S, Gill MA, Stokes J, Liu AH, Gruchalla RS, Cohen RT, Makhija M, Khurana Hershey GK, O'Connor GT, Pongracic JA, Sherenian MG, Rivera-Spoljaric K, Zoratti EM, Teach SJ, Kattan M, Dutmer CM, Kim H, Lamm C, Sheehan WJ, Segnitz RM, Dill-McFarland KA, Visness CM, Becker PM, Gern JE, Sorkness CA, Busse WW, Altman MC; US National Institute of Allergy and Infectious Disease's Inner City Asthma Consortium. Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA (MUPPITS-2): a randomised, double-blind, placebo-controlled, parallel-group trial. Lancet. 2022 Aug 13;400(10351):502-511. doi: 10.1016/S0140-6736(22)01198-9.