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Trial record 1 of 1 for:    NCT04053634
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Efficacy and Safety of Benralizumab in Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With a History of Frequent Exacerbations (RESOLUTE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04053634
Recruitment Status : Recruiting
First Posted : August 12, 2019
Last Update Posted : May 16, 2023
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Description
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Brief Summary:

Phase 3 study to evaluate the efficacy and safety of a benralizumab in patients with moderate to very severe COPD with a history of frequent COPD exacerbations and elevated peripheral blood eosinophils (≥300/μL).

Eligible patients must have a history of ≥2 moderate and/or severe COPD exacerbations in the previous year despite receiving triple (ICS/LABA/LAMA) background therapy for at least 3 months and ICS-based dual inhaled treatment for the remainder of the year. Eligible patients must also have an elevated blood eosinophil count.

The treatment period will be of variable duration and will continue until the last patient has the opportunity to complete a minimum of 56 weeks, at which point all patients will complete the study. The primary endpoint will be analyzed at Week 56.


Condition or disease Intervention/treatment Phase
Chronic Obstructive Pulmonary Disease Biological: Benralizumab Biological: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 642 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Chronic-dosing, Parallel-group, Placebo-controlled Phase 3 Study to Evaluate the Efficacy and Safety of Benralizumab 100 mg in Patients With Moderate to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With a History of Frequent COPD Exacerbations and Elevated Peripheral Blood Eosinophils (RESOLUTE)
Actual Study Start Date : August 26, 2019
Estimated Primary Completion Date : June 27, 2025
Estimated Study Completion Date : June 27, 2025

Resource links provided by the National Library of Medicine

MedlinePlus related topics: COPD Lung Diseases

Arms and Interventions
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Arm Intervention/treatment
Experimental: Benralizumab
Administrated subcutaneously (SC) every 4 weeks for the first 3 doses, then every 8 weeks
 Biological: Benralizumab
Benralizumab solution for injection in accessorized prefilled syringe (APFS) will be administered subcutaneously (SC) every 4 weeks for the first 3 doses - Weeks 0, 4 and 8, and then every 8 weeks until the end of treatment.
Placebo Comparator: Placebo
Administrated subcutaneously every 4 weeks for the first 3 doses, then every 8 weeks
 Biological: Placebo
Matching placebo will be administered subcutaneously with accessorized prefilled syringe (APFS) every 4 weeks for the first 3 doses - Weeks 0, 4 and 8, and then every 8 weeks until the end of treatment.


Outcome Measures
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Primary Outcome Measures :
  1. Annualized rate of moderate or severe COPD exacerbations [ Time Frame: Over first 56 weeks ]

    Moderate or severe COPD exacerbation is defined by symptomatic worsening of COPD requiring:

    • Use of systemic corticosteroids for at least 3 days; and/or
    • Use of antibiotics; and/or
    • An inpatient hospitalization or death due to COPD


Secondary Outcome Measures :
  1. Annualized rate of severe COPD exacerbations [ Time Frame: Minimum of 1 year and an average of 2 years ]
    A severe COPD exacerbation is defined by symptomatic worsening of COPD requiring an inpatient hospitalization or results in death due to COPD

  2. Annualized rate of COPD exacerbations that are associated with an emergency room/emergency department visit or a hospitalization [ Time Frame: Minimum of 1 year and an average of 2 years ]
  3. Time to first COPD exacerbation [ Time Frame: During first 56 weeks ]
  4. Change from baseline in SGRQ total and domain scores [ Time Frame: up to 56 weeks ]
    St. George's Respiratory Questionnaire (SGRQ)

  5. Change from baseline in E-RS:COPD total and domain scores [ Time Frame: up to 56 weeks ]
    Evaluating Respiratory Symptoms in COPD (E-RS:COPD)

  6. Change from baseline in pre-dose/pre-bronchodilator FEV1 [ Time Frame: up to 56 weeks ]
    FEV1 is the Forced expiratory volume in one second at study site

  7. All cause and respiratory-related mortality rate [ Time Frame: Minimum of 1 year and an average of 2 years ]
  8. Annual rate of hospitalizations due to COPD [ Time Frame: Minimum of 1 year and an average of 2 years ]
  9. Serum benralizumab concentration as a measure of pharmacokinetics [ Time Frame: up to 56 weeks ]
  10. Anti-drug antibodies (ADA) as a measure of immunogenicity [ Time Frame: up to 56 weeks ]
  11. Change from baseline in CAT total score [ Time Frame: up to 56 weeks ]
    Chronic Obstructive Pulmonary Disease assessment tool (CAT)

  12. Length of hospital stay [ Time Frame: Minimum of 1 year and an average of 2 years ]
  13. ICU (Intensive Care Unit) days [ Time Frame: Minimum of 1 year and an average of 2 years ]
  14. Annual rate of hospitalizations and emergency department visits combined [ Time Frame: Minimum of 1 year and an average of 2 years ]
  15. Annual rate of unscheduled outpatient visits including unscheduled visits to study sites [ Time Frame: Minimum of 1 year and an average of 2 years ]
  16. Annual rate of unscheduled healthcare encounters [ Time Frame: Minimum of 1 year and and average of 2 years ]

Other Outcome Measures:
  1. Safety and tolerability of benralizumab in patients with moderate to very severe COPD [ Time Frame: Minimum of 1 year and average of 2 years ]
    AEs, vital signs, clinical laboratory, and ECG


Eligibility Criteria
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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:   40 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provision of informed consent
  2. Age 40 to 85 years
  3. Male and/or female.
  4. Current or former smoker with a tobacco history of ≥10 pack-years.
  5. History of moderate to very severe COPD with a post-bronchodilator FEV1/FVC<0.70 and FEV1 ≤65% of predicted normal value.

  6. Documented history of 2 or more COPD exacerbations that required treatment with systemic corticosteroids and/or hospitalization within 52 weeks prior to enrollment.

    1. Exacerbations treated with antibiotics alone are excluded unless accompanied by treatment with systemic corticosteroids and/or hospitalization.
    2. Hospitalization is defined as an inpatient admission ≥24 hours
    3. Previous exacerbations should be confirmed to have occurred while on stable triple therapy for COPD.
    4. At least one qualifying COPD exacerbation should occur while on stable uninterrupted triple therapy prior to enrolment.

  7. Documented use of triple (ICS/LABA/LAMA) background therapy for COPD for ≥3 months immediately prior to enrollment.

    1. Treatment with at least double inhaled therapy containing ICS (e.g. ICS/LABA or ICS/LAMA) for the remaining of 52 weeks prior to enrolment. Use of LABA/LAMA is allowed if ICS cannot be tolerated.
    2. ICS in a dose approved for COPD or equivalent to ≥250 mcg of fluticasone propionate daily.
    3. Total cumulative duration of not being on double or triple background therapy must not exceed 2 months.
    4. Stable therapy/doses for the last 3 months prior to randomization.
  8. Blood eosinophil count ≥300/μL at screening and documented historical eosinophil count of ≥150/μL within 52 weeks of enrollment (or repeated testing during run-in).
  9. CAT total score ≥15 at Visit 1.
  10. Negative pregnancy test for females of childbearing potential (WOCBP) at Visit 1.
  11. Women of childbearing potential (WOCBP) must agree to use a highly effective method of birth control from enrollment throughout the study and within 12 weeks after last dose of IP.

Women not of childbearing potential are defined as women who are either permanently sterilized or postmenopausal (confirmed by FSH test for women <50 years).

Exclusion Criteria:

  1. Clinically important pulmonary disease other than COPD
  2. Current diagnosis of asthma, prior history of asthma or asthma-COPD overlap according to GINA/GOLD. Childhood history of asthma is allowed and defined as asthma diagnosed and resolved before the age of 18.
  3. Radiological findings of a respiratory disease other than COPD contributing to respiratory symptoms. Solitary pulmonary nodules without appropriate follow up or findings of acute infection.
  4. Another pulmonary or systemic disease associated with elevated peripheral eosinophil counts.
  5. Any unstable disorder that could affect patient safety, study findings or the patient's ability to complete the study.
  6. Any clinically significant abnormal findings in physical examination, vital signs, ECG, laboratory tests could affect patient safety, study findings or the patient's ability to complete the study.
  7. Cor pulmonale and/or right ventricular failure.
  8. Long-term treatment with oxygen >4.0 L/min and/or oxyhemoglobin saturation <89% while breathing supplemental oxygen.
  9. Use of any non-invasive positive pressure ventilation device (NIPPV). Note: use of CPAP for Sleep Apnea Syndrome is allowed.
  10. Known immunodeficiency disorder, including positive HIV-1/2 testing.
  11. Active liver disease. Chronic stable hepatitis B and C (including positive HBsAg or hepatitis C antibody testing), or other stable chronic liver disease are acceptable.
  12. ALT or AST ≥3 times the upper limit of normal, confirmed by repeated testing during the run-in period.
  13. Helminth parasitic infection within 24 weeks prior to enrollment, not treated or failed to respond to standard of care therapy.
  14. Alcohol or drug abuse within the past year, which may compromise the study data.
  15. Malignancy, current or within the past 5 years, except for adequately treated non invasive basal cell and squamous cell carcinoma of the skin and cervical carcinoma-in-situ treated with apparent success more than 1 year prior to Visit 1. Suspected malignancy or undefined neoplasms.
  16. Evidence of active tuberculosis, as judged by investigator. Patients with a recent (within 2 years) first-time or newly positive PPD or Quantiferon test need to complete an appropriate course of treatment before enrollment. Evaluation will be according to the local standard of care.
  17. Participation, or planned participation, in intensive COPD rehabilitation program (maintenance phase of a rehabilitation is allowed).
  18. History of surgical or endoscopic lung volume reduction within the 6 months prior to enrollment. History of partial or total lung resection (single lobe or segmentectomy is acceptable).
  19. Scheduled major surgical procedure during the study. Minor elective procedures are allowed.
  20. History of anaphylaxis to any biologic therapy or vaccine.
  21. Receipt of blood products or immunoglobulins within 30 days prior to randomization.
  22. Receipt of marketed or investigational biologic product within 4 months or 5 half-lives prior to randomization, whichever is longer. Exception: Patients on stable therapy for 3 months before randomization who intend to stay on treatment throughout the study with marketed biologic products that are not likely to interfere with the safety assessment and/or efficacy of benralizumab, for example, for the treatment of osteoporosis, migraine, pain, diabetes, obesity, ocular, cardiovascular, or metabolic diseases, can participate in the study.
  23. Receipt of live attenuated vaccines 30 days prior to randomization.
  24. Chronic use of immunosuppressive medication or expected need for chronic use during the study.
  25. Chronic use of antibiotics if duration of treatment is <9 months prior to randomization. Chronic macrolide or other antibiotic therapy is allowed provided the patient has been on stable dose/regimen for ≥9 months prior to randomization and has had ≥2 COPD exacerbations while on stable therapy.
  26. Receipt of any investigational non-biologic product within 30 days or 5 half-lives prior to enrollment.
  27. Receipt of benralizumab within 12 months prior to enrollment.
  28. Known history of allergy or reaction to any component of the IP formulation.
Contacts and Locations
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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): NCT04053634


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Gerard Criner, MD Temple University School of Medicine, 3401 North Broad Street, Suite 745 PP, Philadelphia, PA 19140
More Information
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Additional Information:

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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04053634    
Other Study ID Numbers: D3251C00014
2019-001800-39 ( EudraCT Number )
First Posted: August 12, 2019    Key Record Dates
Last Update Posted: May 16, 2023
Last Verified: May 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles.
Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access.
URL: https://astrazenecagroup-dt.pharmacm.com/DT/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 AstraZeneca:
Chronic Obstructive Pulmonary Disease
COPD
benralizumab
Fasenra
ICS
 inhaled corticosteroids
exacerbations
Lung Disease
LABA/LAMA
Additional relevant MeSH terms:
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Lung Diseases
Lung Diseases, Obstructive
Pulmonary Disease, Chronic Obstructive
Respiratory Tract Diseases
Chronic Disease
 Disease Attributes
Pathologic Processes
Benralizumab
Anti-Asthmatic Agents
Respiratory System Agents