BENRALIZUMAB for Severe eosinophilic asthma|Eosinophilic asthma

Inclusion criteria

• {"criterion_text":"-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)"}
• {"criterion_text":"-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 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, ie. 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"}
• {"criterion_text":"-Acceptable inhaler technique, as judged by the investigator."}
• {"criterion_text":"-ACQ-6 >1.5"}
• {"criterion_text":"-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"}
• {"criterion_text":"-Fewer than 12 exacerbations within the 6 months prior to Visit 3"}
• {"criterion_text":"-Male or female aged 18 through 70 years at the time of Visit 1"}
• {"criterion_text":"-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"}
• {"criterion_text":"-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. -For ICS plus LABA combination preparations, highest-strength maintenance doses approved in the given country will meet this criterion. -If the ICS and LABA are given by separate inhalers, then the participant must be on a high daily ICS dose during the last 3 months prior to Visit 1(see Appendix D for high daily ICS doses by formulation)."}
• {"criterion_text":"-Morning pre-BD FEV1 ≥ 50 to < 80% of PNV and ≥ 1 L at Visit 2, or morning pre-BD FEV1 ≥ 50 to < 90% of PNV, if documented historical pre-BD FEV1 value (within 12 months prior to screening visit) was < 80% of PNV. One retest is allowed"}
• {"criterion_text":"-A blood eosinophil count meeting any of 3 criteria below: - ≥ 300 cells/μL during screening at Visit 1 or Visit 2, OR - ≥ 220 to < 300 cells/μL during screening at Visit 1 or Visit 2 and documented eosinophil count of ≥ 300 cells/μL in the past 12 months, 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"}
• {"criterion_text":"-Weight of ≥40 kg"}
• {"criterion_text":"-Negative serum pregnancy test for female participants of childbearing potential at Visit 1"}
• {"criterion_text":"-Negative urine pregnancy test in female participants of childbearing potential prior to randomization and administration of IP"}

Exclusion criteria

• {"criterion_text":"-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."}
• {"criterion_text":"-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."}
• {"criterion_text":"-In participants undergoing bronchoscopy, a history of allergies or adverse drug reactions to medications used for pre-bronchoscopy procedures."}
• {"criterion_text":"-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."}
• {"criterion_text":"-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."}
• {"criterion_text":"-Alcohol or drug abuse (past or present) or any conditions associated with poor compliance."}
• {"criterion_text":"-Participants who are scheduled to be admitted to hospital or undergo inpatient surgery during the study."}
• {"criterion_text":"-History of anaphylaxis to any biologic therapy."}
• {"criterion_text":"-Known history of allergy or reaction to any component of the IP formulation"}
• {"criterion_text":"-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"}
• {"criterion_text":"-A history of known immunodeficiency disorder including a positive human immunodeficiency virus test."}
• {"criterion_text":"-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."}
• {"criterion_text":"-Any medical condition that requires chronic treatment with chronic anti-coagulation, chronic aspirin, or anti-platelet therapy (in participants undergoing bronchoscopy)."}
• {"criterion_text":"-Use of anticoagulants within 4 weeks prior to randomization into the study (in participants undergoing bronchoscopy)."}
• {"criterion_text":"-In participants undergoing bronchoscopy, use of non-steroidal antiinflammatory drugs within 72 hours before or aspirin within 7 days of randomization"}
• {"criterion_text":"-Use of chronic (i.e. >4 weeks) immunosuppressive medication within 3 months prior to the date informed consent is obtained."}
• {"criterion_text":"-Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained."}
• {"criterion_text":"-Receipt of any marketed or investigational biologic for the treatment of asthma within 4 months or 5 half-lives prior to the date informed consent is obtained, whichever is longer."}
• {"criterion_text":"-Previously received benralizumab. Participants that participated in other studies with benralizumab but have been confirmed to have received placebo are eligible."}
• {"criterion_text":"-Receipt of live attenuated vaccines 30 days prior to the date of randomization. Receipt of inactive/killed vaccinations is allowed provided they are not administered within 1 week before/after any IP administration."}
• {"criterion_text":"-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."}
• {"criterion_text":"-Receipt of bronchial thermoplasty in the last 24 months prior to Visit 1."}
• {"criterion_text":"-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."}
• {"criterion_text":"-Receipt of any investigational non-biologic within 30 days or 5 halflives prior to the date informed consent is obtained, whichever is longer."}
• {"criterion_text":"-Any clinically significant abnormal findings, which in the opinion of the Investigator, may put the particpant at risk, or may influence the results of the study, or the participant's ability to complete the entire duration of the study."}
• {"criterion_text":"-Alanine aminotransferase or aspartate aminotransferase level ≥3 times the upper limit of normal, confirmed by repeated testing during the screening period."}
• {"criterion_text":"-Currently pregnant, breastfeeding or lactating women."}
• {"criterion_text":"-Blood draws of 100 mL or more within 45 days prior to enrolment in the study."}
• {"criterion_text":"-Radiological findings suggestive of a respiratory disease other than asthma that is contributing to the participant's respiratory symptoms."}

Primary endpoints

• {"endpoint_text":"-The change, expressed as a percentage from baseline to end of treatment (EOT) in eosinophil numbers, expressed as number/mm2 in submucosa.","definition_or_measurement_approach":"Eosinophil numbers in submucosa measured in endobronchial biopsies; change expressed as percentage from baseline to EOT."}
• {"endpoint_text":"-The change, expressed as a percentage, from baseline to EOT in airway WA% as the overall median for airway generations 3 and 4 combined. Supportive measure: Change, expressed as a percentage, from baseline to EOT in airway lumen area (LA), airway wall area (WA) and airway wall thickness (WT).","definition_or_measurement_approach":"Airway WA% measured by quantitative computed tomography (QCT) imaging for airway generations 3 and 4 combined; supportive QCT measures include LA, WA, and WT changes from baseline to EOT."}

Denmark

Earliest CTIS Part Ii Submission Date

18-02-2024

Latest Decision Or Authorization Date

14-03-2024

Processing Time Days

25

Number Of Sites

3

Number Of Participants

19

Sweden

Earliest CTIS Part Ii Submission Date

18-02-2024

Latest Decision Or Authorization Date

15-03-2024

Processing Time Days

26

Number Of Sites

1

Number Of Participants

8

Primary sponsor

Full Name

Astrazeneca AB

Organisation Type

Pharmaceutical company

Country Of Registered Address

Sweden