A Study to Evaluate the Effect of Benralizumab on Structural and Lung Function Changes in Severe Eosinophilic Asthmatics

Overview

About this study

The purposes of this study are to evaluate the effect of benralizumab on submucosal eosinophils in endobronchial biopsies as measured by major basic protein (MBP) staining, and to evaluate the effect of treatment with benralizumab on airway wall dimensions as measured by QCT imaging.

 

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

  • Able to understand and give written informed consent and has signed a written informed consent form (ICF) approved by the Investigator’s Institutional Review Board (IRB)/Ethics Committee (EC), prior to conducting any study related procedures (including withholding of any asthma medications required for procedures).
  • Male or female, aged 18 through 70 years at the time of Visit 1.
  • History of physician-diagnosed asthma requiring continuous treatment with medium- or high-dose ICS (>250 μg fluticasone propionate dry powder formulation equivalents total daily dose) plus LABA with or without additional controller medication for at least 12 months prior to Visit 1.
  • Documented current treatment with high-dose ICS plus LABA for at least 3 months prior to Visit 1 with or without additional asthma maintenance medication. If the participant is taking ICS plus LABA, the ICS and LABA can be parts of a combination product or given by separate inhalers. The ICS dose during the last 3 months prior to Visit 1 must have been >500 μg/day fluticasone propionate dry powder formulation or equivalent daily.
  • Morning pre-BD FEV1 ≥50 to <80% of predicted normal value (PNV) and ≥1 L at Visit 2.
  • A blood eosinophil count of:
    • ≥ 300 cells/μL during screening at Visit 1 or Visit 2; OR
    • ≥ 150 to < 300 cells/μL during screening at Visit 1 or Visit 2 plus one of the following:
      • presence of nasal polyps; or
      • pre-BD FVC < 65% predicted at Visit 2; or
      •  sputum eosinophil count of ≥ 2% at Visit 2.
  • Weight of ≥ 40 kg.
  • Negative serum pregnancy test for female participants of childbearing potential at Visit 1.
  • Negative urine pregnancy test in female participants of childbearing potential prior to randomization and administration of IP.
  • Women are authorized to participate if they meet the following criteria:
    • Female participants who cannot bear children as evidenced by:
      • Women “not of childbearing potential” are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal;
      • Women will be considered postmenopausal if they have been amenorrhoeic for ≥ months prior to the planned date of randomization without an alternative medical cause.
  • The following age-specific requirements apply:
    • Women < 50 years old will be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone (FSH) levels in the postmenopausal range. Until FSH is documented to be within menopausal range treat the participant as WOCBP;
    • Women ≥ 50 years old will be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment;
    • If criteria not met, participant should be regarded as having child bearing potential.
  • Female participant capable of having children and both of the following conditions are met:
    • Have a negative urine pregnancy test prior to administration of the IP; and
    • Must agree to use a highly effective method of birth control (confirmed by the investigator) from randomization throughout the study duration and within 12 weeks after last dose of IP. Highly effective methods ( those that can achieve a failure rate of less than 1% per year when used consistently and correctly) include:
      • Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation- oral, intravaginal, or transdermal;
      • Progestogen-only hormonal contraception associated with inhibition of ovulation- oral, injectable, or implantable;
      • Intrauterine device (IUD);
      • Intrauterine hormone-releasing system (IUS);
      • Bilateral tubal occlusion;
      • Sexual abstinence; i.e. refraining from heterosexual intercourse (The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study and the preferred and usual lifestyle of the participant);
      • Vasectomized sexual partner provided that partner is the sole sexual partner of the WOCBP study participant and that the vasectomized partner has received medical assessment of the surgical success.
  • Acceptable inhaler technique, as judged by the Investigator.
  • ACQ-6 > 1.5.
  • Compliance with inhaled asthma maintenance medication > 70% (calculated in the period.from Visit 2 to Visit 3). The screening/run-in period may be extended to accommodate this criterion.
  • Fewer than 12 exacerbations within the 6 months prior to Visit 3.

Exclusion Criteria:

  • Clinically important pulmonary disease other than asthma (including but not limited to active lung infection, chronic obstructive pulmonary disease, bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia) or participants who have ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts (e.g., allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss syndrome and hypereosinophilic syndrome).
  • Life-threatening asthma, defined as episodes requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma related syncopal episodes within the 12 months prior to Visit 1.
  • A history of allergies or adverse drug reactions to medications used for pre-bronchoscopy procedures (e.g., benzodiazepines, propofol, sedatives etc).
  • Any disorder, including but not limited to cardiovascular, gastrointestinal, hepatic, renal,
  • neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric,
  • or major physical impairment that is not stable in the opinion of the Investigator and could:
    • Affect the safety of the participant during the study;
    • Influence the findings of the studies or their interpretations;
    • Impede the participant’s ability to complete the entire duration of the study.
  • Current smokers. Ex-smokers must not have smoked for a minimum of 12 months and should not have a smoking history > 15 pack-years at Visit 1. Participants who use ecigarettes or smoke marijuana will also be excluded from the study.
  • Alcohol or drug abuse (past or present) or any conditions associated with poor compliance.
  • Participants who are scheduled to be admitted to hospital or undergo inpatient surgery during the study.
  • History of anaphylaxis to any biologic therapy.
  • Known history of allergy or reaction to any component of the IP formulation.
  • History of cancer:
    • Participants who have had basal cell carcinoma, localized squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible provided that the participant is in complete remission and curative therapy was completed at least 12 months prior to the date informed consent is obtained;
    • Participants who have had other malignancies are eligible provided that the participant is in complete remission and curative therapy was completed at least 5 years prior to the date informed consent is obtained.
  • A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with, or has failed to respond to standard of care therapy.
  • A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test.
  • Current active liver disease, except for chronic stable hepatitis B and C (including positive testing for hepatitis B surface antigen (HBsAg) or hepatitis C antibody), or other stable chronic liver disease are acceptable if participant otherwise meets eligibility criteria. Stable chronic liver disease should generally be defined by the absence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice, or cirrhosis
  • Any medical condition that requires chronic treatment with chronic anti-coagulation, chronic aspirin or anti-platelet therapy.
  • Use of anticoagulants (e.g., warfarin, heparin or novel oral anticoagulants) within 4 weeks prior to randomization into the study. If there is a need for a short-term, acute use of anticoagulants prior to randomization, the screening/run-in period may be extended to accommodate this criterion.
  • Use of non-steroidal anti-inflammatory drugs (NSAIDs) within 72 hours before or aspirin (as needed) within 7 days of randomization (Visit 3), or longer or as judged by the Investigator. The screening/run-in period may be extended to accommodate this criterion.
  • Use of chronic (i.e., > 4 weeks) immunosuppressive medication (including but not limited to:
    • methotrexate, troleandomycin, cyclosporine, azathioprine, intramuscular long-acting depot corticosteroid, chronic systemic corticosteroid including OCS, or any experimental anti-inflammatory therapy) within 3 months prior to the date informed consent is obtained.
  • Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained.
  • Receipt of any marketed (e.g., omalizumab, mepolizumab and reslizumab) or investigational
  • biologic within 4 months or 5 half-lives prior to the date informed consent is obtained, whichever is longer.
  • Previously received benralizumab (MEDI-563). Participants that participated in other studies with benralizumab but have been confirmed to have received placebo are eligible.
  • Receipt of live attenuated vaccines 30 days prior to the date of randomization. Receipt of inactive/killed vaccinations (e.g. inactive influenza) is allowed provided they are not administered within 1 week before/after any IP administration.
  • Change to allergen immunotherapy or new allergen immunotherapy within 30 days prior to the date of informed consent and anticipated changes in immunotherapy during the study.
  • Receipt of bronchial thermoplasty in the last 24 months prior to Visit 1.
  • Participation in an interventional clinical study during the past 3 months or participants previously randomized into this study. If it is documented that the participant was known to be on placebo treatment of a completed study, then a 3-month period is not required.
  • Receipt of any investigational non-biologic within 30 days or 5 half-lives prior to the date informed consent is obtained, whichever is longer.
  • Any clinically significant abnormal findings in physical examination, vital signs, electrocardiogram (ECG), hematology or clinical chemistry during run-in period, which in the opinion of the Investigator, may put the participant at risk because of his/her participation in the study, or may influence the results of the study, or the participant’s ability to complete the entire duration of the study.
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥ times the upper limit of normal (ULN), confirmed by repeated testing during the screening period.
  • Currently pregnant, breastfeeding or lactating women. A serum pregnancy test will be performed for WOCBP at Visit 1 and a urine pregnancy test must be performed for WOCBP prior to randomization and administration of IP. A positive urine test result must be confirmed with a serum pregnancy test. If the serum test is positive, the participant should be excluded.
  • Blood draws of 100 mL or more within 45 days prior to enrolment (Visit 1) in the study.
  • AstraZeneca staff involved in the planning and/or conduct of the study.
  • Employees of the study center or any other individuals involved with the conduct of the study, or immediate family members of such individuals.
  • Radiological findings suggestive of a respiratory disease other than asthma that is contributing to the participant’s respiratory symptoms. Radiological findings of solitary pulmonary nodules ≥6mm without appropriate follow up and demonstration of at least 2 years stability as per standard of care, or findings suggestive of acute infection. Screening period may be extended for cases of acute infection and based on case by case discussion between Investigator and AZ Study Physician.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Karina Keogh, M.D.

Closed-enrolling by invitation

What is this? (?)
"Close"
Not open to everyone who meets the eligibility criteria, but only those invited to participate by the study team.

Contact information:

Pulmonary Clinical Research Unit

(800) 753-1606

PCRUE18@mayo.edu

More information

Publications

Publications are currently not available
.
CLS-20526653

Mayo Clinic Footer