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

NCT ID: NCT03292588

Last Updated: 2022-07-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 335 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-07
• Study Completion Date: 2021-04-20

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.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Mepolizumab

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

Group Type: EXPERIMENTAL

Mepolizumab

Intervention Type: 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.

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: 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.

Interventions

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.

Intervention Type: BIOLOGICAL

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.

Intervention Type: DRUG

Other Intervention Names

Nucala®; anti-Interleukin 5 (IL5) antagonist monoclonal antibody; Placebo for Mepolizumab

Eligibility Criteria

Inclusion Criteria

• 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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Inner-City Asthma Consortium

NETWORK

Sponsor Role: collaborator

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Rho Federal Systems Division, Inc.

INDUSTRY

Sponsor Role: collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Daniel J Jackson, MD

Role: STUDY_CHAIR

University of Wisconsin, Madison

William W Busse, MD

Role: STUDY_CHAIR

University of Wisconsin, Madison

Locations

Children's Hospital Colorado

Aurora, Colorado, United States

Children's National Medical Center

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

Ann and Robert Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Boston Medical Center

Boston, Massachusetts, United States

Henry Ford Health System

Detroit, Michigan, United States

St. Louis Children's Hospital

St Louis, Missouri, United States

Columbia University Medical Center

New York, New York, United States

Cincinnati Children's Hospital

Cincinnati, Ohio, United States

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 40897727 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 40658400 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 35964610 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases (NIAID) website

https://www.niaid.nih.gov/about/dait

Division of Allergy, Immunology, and Transplantation (DAIT) website

Other Identifiers

UM1AI114271

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NIAID CRMS ID#: 38189

Identifier Type: OTHER

Identifier Source: secondary_id

DAIT ICAC-30

Identifier Type: -

Identifier Source: org_study_id