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Prevention of Asthma Exacerbations Using Dupilumab in Urban Children and Adolescents (PANDA)

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ClinicalTrials.gov Identifier: NCT05347771
Recruitment Status : Recruiting
First Posted : April 26, 2022
Last Update Posted : June 6, 2022
Sponsor:
Collaborators:
Childhood Asthma in Urban Settings (CAUSE)
Regeneron Pharmaceuticals
Rho Federal Systems Division, Inc.
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief Summary:
This is a multi-center, double-blind, placebo-controlled, randomized trial of dupilumab adjunctive therapy for prevention of asthma exacerbations in urban children and adolescents with T2-high exacerbation-prone asthma.

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

Detailed Description:

Protocol CAUSE-01 PANDA is a multicenter, double-blind, placebo-controlled, randomized trial of dupilumab adjunctive therapy for the reduction of asthma exacerbations in urban children and adolescents 6 to 17 years with T2-high exacerbation-prone asthma. Approximately 240 participants will be randomized 2:1 to one of two study arms: 1) guidelines-based asthma treatment + dupilumab, or 2) guidelines-based asthma treatment + placebo. Study treatment will continue for 1 year with an additional 3 months of follow-up following completion of study treatment.

An initial Screening Visit will be followed by a 4-week run-in period. After the run-in, participants who continue to meet eligibility criteria will be randomized to one of the 2 treatment arms and receive their first injection. Over the next 2 weeks, participants will return to the clinic for 3 early treatment response visits. Participants will receive injections of dupilumab or placebo administered subcutaneously every two weeks (Q2W) over 12 months. Each participant will have Evaluation and Management (E&M) visits every 3 months where their asthma and rhinitis will be assessed and adjustments made to their medications based on asthma guidelines.

Participants will be asked to monitor and self-report cold symptoms throughout the treatment period. Participants will be asked to complete up to three paired cold visits. At the time of a cold, participants will be asked to come into the clinic for collection of blood and nasal secretions for associated mechanistic studies. Approximately three days after the clinic visit, participants will complete symptom assessments and will be asked to collect nasal samples at home.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 240 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Prevention of Asthma Exacerbations Using Dupilumab in Urban Children and Adolescents (PANDA) (CAUSE-01)
Actual Study Start Date : May 4, 2022
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : March 31, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma
Drug Information available for: Dupilumab

Arm Intervention/treatment
Experimental: Dupilumab

Participants between 12-17 years of age, will receive an initial dose of 600 mg (two 300 mg injections) followed by 300 mg given every other week (Q2W).

Participants between 6-11 years of age will not complete a loading dose and will receive injections based on their body weight:

Participants with a body weight of 15 kg to less than 30 kg, will receive 100mg Q2W.

Participants with a body weight of 30 kg or more, will receive 200 mg Q2W.

Drug: Dupilumab
Dupilumab is a recombinant DNA-derived humanized IgG4ĸ monoclonal antibody that selectively binds to anti IL-4R monoclonal antibody (mAb).
Other Names:
  • Dupixent
  • IL4Ra mAb

Placebo Comparator: Placebo

Participants between 12-17 years of age, will receive an initial dose of placebo (two injections) followed by a placebo injection given every other week (Q2W).

Participants between 6-11 years of age will not receive an initial loading dose of placebo and will receive injections Q2W based on their body weight.

Drug: Placebo
The composition of the placebo for dupilumab is the same as the active study drug without the dupilumab.
Other Name: Placebo for Dupilumab




Primary Outcome Measures :
  1. Number of asthma exacerbations during the 12-month treatment period [ Time Frame: Week 4 (Treatment initiation) - Week 54 (Completion of treatment) ]
    Asthma exacerbation defined as a prescription of a course of systemic steroids by a clinician or initiation of a course of systemic steroids by a participant to prevent a serious asthma outcome. 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 dosage: the course for prednisone, prednisolone, or methylprednisolone will be at least 20 mg daily dose for 3 of 5 consecutive days. The course for dexamethasone will be at least a 10 mg single daily dose. If a corticosteroid burst for the treatment of an asthma exacerbation is prescribed by a non-CAUSE clinician, it will be counted regardless of dose.


Secondary Outcome Measures :
  1. Pulmonary Function Measured by Spirometry: Forced Expiratory Volume in 1 Second (FEV1) % Predicted [ Time Frame: Week 4 to Week 68 ]

    FEV1 is air volume exhaled in 1 second during spirometry. 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.


  2. Days with symptoms, nights with symptoms, and day and night albuterol use. [ Time Frame: Week 4 to Week 68 ]

    Number of days with asthma symptoms as defined by the participant report of daytime asthma symptoms over the preceding 14-day period.

    Number of nights with asthma symptoms as defined by participant report of nighttime asthma symptoms over the preceding 14-day period.

    Number of days with albuterol use as defined by participant report of days of albuterol (bronchodilator) use over the preceding 14-day period.

    Number of nights albuterol use as defined by participant report of nights of albuterol (bronchodilator) use over the preceding 14-day period.


  3. Asthma control measured by the Asthma Control Questionnaire-5 [ Time Frame: Week 4 to Week 60 ]
    The Asthma Control Questionnaire-5 is a validated tool that will be used to assess overall asthma control over the last 4 weeks. The Range is 0-6, with higher scores indicating worse asthma control.

  4. Time to first asthma exacerbation [ Time Frame: Week 4 to Week 68 ]
    Time between initiation of treatment and first asthma exacerbation or the end of participant follow-up visits.

  5. Quality of life as measured by the PROMIS Asthma Impact Short Forms (Pediatric or Parent Proxy). [ Time Frame: Week 4 to Week 68 ]
    As measured by the pediatric patient-reported (ages 8-17) or proxy-reported (ages 6-7) PROMIS Asthma Impact Short Forms.

  6. Asthma burden as measured by Combined Asthma Severity Index (CASI) [ Time Frame: Week 4 to Week 68 ]
    The Composite Asthma Severity Index (CASI) is a comprehensive severity scale combining multiple facets of asthma severity: impairment, risk, and treatment. The CASI score ranges from 0 to 20 points, with higher scores indicating higher levels of severity, and includes 5 domains: day symptoms and albuterol use, night symptoms and albuterol use, controller treatment, lung function measures, and exacerbations.

  7. Rhinitis symptoms as measured by Modified Rhinitis Symptoms Utility Index (MRSUI) [ Time Frame: Week 4 - Week 68 ]
    The Modified Rhinitis Symptom Utility Index (MRSUI), assesses the frequency and severity (degree of bothering: not bothered, somewhat bothered, bothered a lot) of the participant's (1) stuffy or blocked nose, (2) runny nose, (3) sneezing, (4) itchy, watery eyes, and (5) itchy nose or throat over the preceding 14-day period.

  8. Related adverse events and serious adverse events in the course of treatment [ Time Frame: Week 4 to Week 68 ]

    The number of adverse events (AEs) by severity and relationship to study drug will be used to assess safety.

    The number of serious adverse events (SAEs) by severity and relationship to study drug will be used to assess safety.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  1. Participant and/or parent guardian must be able to understand and provide informed consent and age-appropriate assent
  2. Are male and female aged 6-17 years at Visit 0
  3. Participant has a primary place of residence in one of the pre-selected recruitment census tracts as outlined in the Protocol CAUSE01 Manual of Operations (MOP). Participants who do not live in the pre-selected census tracts but live within the Office of Management and Budget (OMB) defined Metropolitan Statistical Area and have publicly funded health insurance will qualify for inclusion.
  4. Participant has a diagnosis of asthma made > 1 year prior to recruitment. Participants 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.
  5. Participant has had at least two asthma exacerbations in the prior year (defined as a requirement for systemic corticosteroids and/or hospitalization).
  6. At Visit 0 (screening), participant must have the following requirement for asthma controller medication:

    1. Participants aged 6 to 11 years: treatments with at least fluticasone 250 mcg dry powder inhaler (DPI) one puff twice daily or its equivalent.
    2. Participants aged 12 years and older, treatment with at least fluticasone 250 mcg plus long-acting beta agonist (LABA) DPI one puff twice daily or its equivalent.
  7. Have peripheral blood eosinophils ≥150 cells/mcl and/or FeNO ≥ 20ppb obtained at Visit 0 or via another CAUSE protocol within 6 months.
  8. Are able to perform acceptable and repeatable spirometry per American Thoracic Society (ATS) criteria prior to randomization.
  9. Have documentation of current medical insurance with prescription coverage at Visit 0.

Exclusion Criteria:

  1. Parent or guardian is not able or willing to give written informed consent or comply with study protocol.
  2. Have concurrent medical problems that would require systemic corticosteroids or other immunomodulators during the study.
  3. Are currently receiving immunotherapy.
  4. Are currently receiving treatment with a biologic therapy or have received a biologic therapy within 3 months prior to randomization.
  5. Are currently requiring greater than fluticasone 500 mcg bid plus long-acting beta agonist (LABA) one puff twice daily or its equivalent plus Long-acting muscarinic antagonists (LAMA) and/or individuals using oral corticosteroids daily or every other day for more than 14 days at the time of Visit 0.
  6. Are currently pregnant or lactating, or plan 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 (i.e. oral subcutaneous, mechanical, or surgical contraception). Males who are sexually active must agree to use an acceptable method of birth control (i.e. barrier methods with vaginal spermicide) or have a female partner practicing an approved birth control method for females.
  7. Have a known, pre-existing clinically important lung condition other than asthma.
  8. Have a current malignancy or previous history of cancer in remission for less than 12 months prior to randomization.
  9. Is a current smoker, or is currently using any electronic cigarette or vaping device (e.g. e-cigarette, e- cig, mod, vape pen, JUUL, e-cigar, e-hookah, e-pipe, vape pods).
  10. Have a known immunodeficiency disease.
  11. Have a known, active pre-existing parasitic infection or are undergoing treatment for a parasitic infection. Once the participant has been successfully treated, the participant may be reevaluated.
  12. Use of investigational drugs within 4 weeks of randomization
  13. Have past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the site investigator, may pose additional risks from participation in the 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.
  14. 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 CAUSE- 01 PANDA.
  15. Have a known history of allergic reaction to dupilumab.
  16. Have had a life-threatening asthma exacerbation in the last 2 years requiring intubation, mechanical ventilation or resulting in a hypoxic seizure.
  17. Have received a live (attenuated) vaccine within 4 weeks of Visit 0.
  18. Have an eosinophil count of ≥1500 cells/mcl at Visit 0.

Potential participants may be reassessed as outlined in the Protocol CAUSE-01 MOP.


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): NCT05347771


Locations
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United States, Colorado
Children's Hospital Colorado: Allergy Program Not yet recruiting
Aurora, Colorado, United States, 80045
Contact: Pascuala Pinedo-Estrada    720-777-8077    pascuala.pinedo-estrada@childrenscolorado.org   
United States, District of Columbia
Children's National Medical Center: Children's Research Institute Not yet recruiting
Washington, District of Columbia, United States, 20010
United States, Illinois
Ann & Robert H. Lurie Children's Hospital of Chicago: Division of Allergy and Immunology Not yet recruiting
Chicago, Illinois, United States, 60611
United States, Massachusetts
Boston Children's Hospital: Department of Immunology Not yet recruiting
Boston, Massachusetts, United States, 02215
United States, New York
Icahn School of Medicine at Mount Sinai: Division of Clinical Immunology, Immunology Institute Recruiting
New York, New York, United States, 10029
Contact: Paula Busse    212-241-0764    paula.busse@mssm.edu   
Principal Investigator: Paula Busse         
Columbia University Medical Center: Division of Pediatric Pulmonology Recruiting
New York, New York, United States, 10032
Contact: Marcela Pierce    347-344-3000    mp2648@cumc.columbia.edu   
United States, Ohio
Cincinnati Children's Hospital Medical Center: Asthma Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Anna-Liisa Vockell    513-356-6102    CAUSEScheduling@cchmc.org   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Childhood Asthma in Urban Settings (CAUSE)
Regeneron Pharmaceuticals
Rho Federal Systems Division, Inc.
Investigators
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Study Chair: Daniel J. Jackson, M.D. University of Wisconsin School of Medicine and Public Health; Division of Allergy & Immunology
Additional Information:
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT05347771    
Other Study ID Numbers: DAIT CAUSE-01
First Posted: April 26, 2022    Key Record Dates
Last Update Posted: June 6, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Share data upon study completion in Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
Time Frame: Post database lock
Access Criteria: Open Access
URL: http://www.immport.org/home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
asthma
CAUSE
PANDA
T2
dupilumab
Additional relevant MeSH terms:
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Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs