A Trial of Mepolizumab Adjunctive Therapy for the Prevention of Asthma Exacerbations in Urban Children

NCT03292588 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: DAIT ICAC-30UM1AI114271NIAID CRMS ID#: 38189
• Study Type: interventional
• Target: 335
• Locations: 1 country
• Sites: 9

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.

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

Outcome Measures

Primary Outcomes (1)

• Number of Asthma Exacerbations During the Treatment Period

  Exacerbations were defined as a prescription of a course of systemic corticosteroids by a clinician, initiation of a course of systemic corticosteroids by a participant, or as a hospitalization for asthma. If a participant initiated and completed a course of systemic corticosteroids without clinician involvement, this course was counted only if the study clinician agreed the treatment was warranted, and it met the following dosage: the course for prednisone, prednisolone, or methylprednisolone was at least 20 mg daily dose for 3 of 5 consecutive days. The course for dexamethasone was at least a 10 mg single daily dose. If a corticosteroid burst for the treatment of an asthma exacerbation was prescribed by a non-ICAC clinician, it was counted regardless of dose.

  Up to 12 months

Secondary Outcomes (12)

• Composite Asthma Severity Index (CASI)

  Week 12, 24, 36, 48, 52 after randomization

• Participant Quality of Life Measured Using the Physician Global Assessment Tool

  Week 56

• Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14

  Week 56

• Lung Function as Assessed by Spirometry

  Weeks 12, 24, 36, 48, 52 after randomization

• Lung Function as Assessed by Impulse Oscillometry

  Weeks 12, 24, 36, 48, 52 after randomization

Other Outcomes (9)

• EXPLORATORY: Time to First Respiratory Virus-Induced Exacerbation

  Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)

• EXPLORATORY:Number of Respiratory Virus-Induced Exacerbations

  Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)

• EXPLORATORY:Childhood Asthma Control Test (ACT)/c-ACT

  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)

Study Arms (2)

Mepolizumab

EXPERIMENTAL

Intervention: Mepolizumab plus guidelines-based standard of care asthma treatment.

Biological: Mepolizumab

Placebo

PLACEBO COMPARATOR

Intervention: Placebo for mepolizumab plus guidelines-based standard of care asthma treatment.

Drug: Placebo

Interventions

Mepolizumab BIOLOGICAL

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.

Also known as: Nucala®, anti-Interleukin 5 (IL5) antagonist monoclonal antibody

Mepolizumab

Placebo DRUG

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.

Also known as: Placebo for Mepolizumab

Placebo

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may not qualify if:

• 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.
• 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;

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Inner-City Asthma Consortium: collaborator
• GlaxoSmithKline: collaborator
• Rho Federal Systems Division, Inc.: collaborator

Study Sites (9)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Ann and Robert Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Publications (3)

• Gaberino CL, Segnitz RM, Dill-McFarland KA, Bacharier LB, Calatroni A, Gill MA, Stokes J, Liu AH, Cohen RT, Kumar R, Lang A, Khurana Hershey GK, Sherenian MG, Zoratti EM, Teach SJ, Kattan M, Becker PM, Togias A, Busse WW, Jackson DJ, Altman MC. Mepolizumab alters gene regulatory networks of nasal airway type-2 and epithelial inflammation in urban children with asthma. Nat Commun. 2025 Sep 2;16(1):8191. doi: 10.1038/s41467-025-63629-2.

  PMID: 40897727 DERIVED

• Altman MC, Janczyk T, Murphy RC, Jayavelu ND, Calatroni A, Kattan M, Gill MA, Stokes J, Liu AH, Khurana Hershey GK, Sherenian M, Kumar R, Robison RG, Gruchalla RS, O'Connor GT, Zoratti EM, Teach SJ, Lynch SV, Dill-McFarland KA, Becker PM, Togias A, Gern JE, Bacharier LB, Busse WW, Jackson DJ; Inner City Asthma Consortium and Childhood Asthma in Urban Settings Network. Inflammatory Pathways in Residual Asthma Exacerbations Among Mepolizumab-Treated Urban Children: A Secondary Analysis of a Randomized Clinical Trial. JAMA Pediatr. 2025 Sep 1;179(9):957-970. doi: 10.1001/jamapediatrics.2025.2044.

  PMID: 40658400 DERIVED

• 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.

  PMID: 35964610 DERIVED

Related Links

• National Institute of Allergy and Infectious Diseases (NIAID) website
• Division of Allergy, Immunology, and Transplantation (DAIT) website

MeSH Terms

Conditions

Asthma

Interventions

mepolizumab; Interleukin-5

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Results Point of Contact

• Title: Director, Clinical Research Operations Program
• Organization: DAIT/NIAID

DAITClinicalTrialsGov@niaid.nih.gov

301-594-7669

Study Officials

• Daniel J Jackson, MD

  University of Wisconsin, Madison

  STUDY CHAIR

• William W Busse, MD

  University of Wisconsin, Madison

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2017
• First Posted: September 25, 2017
• Study Start: November 7, 2017
• Primary Completion: April 20, 2021
• Study Completion: April 20, 2021
• Last Updated: July 20, 2022
• Results First Posted: June 21, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will share
• Time Frame: After completion of the trial, within 24 months status post database lock.
• Access Criteria: Registration is available for the Immunology Database and Analysis Portal (ImmPort) at: https://www.immport.org/registration. Submit a rationale for the purpose of requesting study data access. ImmPort is a long-term archive of clinical and mechanistic data, a National Institute of Allergy and Infectious Diseases Division of Allergy, Immunology and Transplantation (NIAID DAIT)-funded data repository. This archive is in support of the NIH mission to share data with the public. Data shared through ImmPort is provided by NIH-funded programs, other research organizations and individual scientists, ensuring these discoveries will be the foundation of future research.

Locations

US (9)