The Effect of Benralizumab on Structural and Lung Function Changes in Patients with Severe Asthma
- Conditions
- Severe eosinophilic asthmaMedDRA version: 21.1Level: LLTClassification code 10068462Term: Eosinophilic asthmaSystem Organ Class: 100000004855Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]
- Registration Number
- EUCTR2018-003391-13-GB
- Lead Sponsor
- AstraZeneca AB
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 81
1. 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).
2. Male or female aged 18 through 70 years at the time of Visit 1.
3. History of physician-diagnosed asthma requiring continuous treatment with medium- or high-dose ICS (>250µg 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.
4. 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.
5. Morning pre-BD FEV1 =50 to <80% of predicted normal value (PNV) and =1L at Visit 2. One re-test is allowed.
6. 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.
7. Weight of =40 kg.
8. Negative serum pregnancy test for female participants of childbearing potential at Visit 1.
9. Negative urine pregnancy test in female participants of childbearing potential prior to randomization and administration of IP.
10. 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 =12 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
1. Clinically important pulmonary disease other than asthma or participants who have ever been diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts.
2. 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.
3. A history of allergies or adverse drug reactions to medications used for pre-bronchoscopy procedures.
4. Any disorders 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, or impede the participant’s ability to complete the entire duration of the study.
5. 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 e-cigarettes or smoke marijuana will also be excluded from the study.
6. Alcohol or drug abuse (past or present) or any conditions associated with poor compliance.
7. Participants who are scheduled to be admitted to hospital or undergo inpatient surgery during the study.
8. History of anaphylaxis to any biologic therapy.
9. Known history of allergy or reaction to any component of the IP formulation.
10. 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
11. 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
12. A history of known immunodeficiency disorder including a positive human immunodeficiency virus test.
13. Current active liver disease, except for chronic stable hepatitis B and C, or other stable chronic liver disease are acceptable if participant otherwise meets eligibility criteria.
14. Any medical condition that requires chronic treatment with chronic anti-coagulation, chronic aspirin or anti-platelet therapy.
15. Use of anticoagulants within 4 weeks prior to randomization in to the study.
16. Use of non-steroidal anti-inflammatory drugs within 72 hours before or aspirin within 7 days of randomization, or longer or as judged by the Investigator.
17. Use of chronic (i.e. >4 weeks) immunosuppressive medication within 3 months prior to the date informed consent is obtained.
18. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained.
19. Receipt of any marketed or investigational biologic within 4 months or 5 half-lives prior to the date informed consent is obtained, whichever is longer.
20. Previously received benralizumab. Participants that participated in other studies with benralizumab but have been confirmed to have received placebo are eligible.
21. Receipt of live attenuated vaccines 30 days prior to the date of randomization. Receipt of inactive/killed vaccinations i
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method