STEP: Phase IIIb study of benralizumab to step-down maintenance therapy in patients with severe eosinophilic asthma - STEP

Inclusion Criteria

• Informed Consent
• 1．Provision of informed consent prior to any study-specific procedures.
• Written informed consent, and assent when applicable for study participation must be obtained prior to any study related procedures being performed (local regulations are to be followed in determining the assent/consent requirements for children and parent[s]/guardian[s]) and according to international guidelines and/or applicable local guidelines.
• Age
• 2. Patient must be aged 12-75 years old, inclusively, at the time of Visit 1(Week -1 to Week 0)
• For those patients, who are 17 on the day of Visit 1(Week -1 to Week 0) but will turn 18 after this day, will be considered an adolescent for the purposes of this study.
• Type of Patient and Disease Characteristics
• 3. Documented history of physician-diagnosed asthma prior to Visit 1
• • Documented post-bronchodilator (post-BD) reversibility in FEV1 of ≥12% and ≥200 mL in FEV1 or positive result of branchial provocation test within 12 months prior to Visit 1. If historical documentation is not available, reversibility must be demonstrated and documented at Visit 1.
• •Prior to screening (Visit 1, Week -1 to Week 0), patients must have either a documented asthma diagnosis for >6 months or a history of ICS/LABA use for >6 months.
• 4. Documented diagnosis of severe eosinophilic asthma (EOS≥150 cells/μL at enrollment, and if EOS 150-<300 cells/μL at enrollment, must have EOS≥300 cells/μL at sometime within 1 year before enrollment)
• 5. Documented current maintenance treatment with MD/HD ICS + LABA with up to one additional controller
• • Other acceptable asthma controller includes LTRA and LAMA
• 6. On stable MD/HD ICS(>250μg fluticasone propionate dry powder formulation equivalents total daily dose) + LABA for ≥2 months prior to enrollment (see Appendix F for medium and high daily ICS doses by formulation)
• 7. For patients on MD ICS/LABA, stable LTRA or LAMA (≥2 weeks) is allowed
• 8. Documented at least one exacerbation in the year prior to enrolment
• • A qualifying historical asthma exacerbation is a symptomatic worsening requiring systemic corticosteroid (i.e., oral, intravenous (IV) or intramuscular; any healthcare setting or temporary increase from a stable maintenance dose of oral corticosteroid) or that resulted in hospitalization or emergency room/urgent care visit.
• ⚫ Source documentation is required for physician-diagnosed asthma, ICS-LABA use and asthma exacerbations over the prior year. A patient verbal history suggestive of asthma symptoms and/or prior asthma exacerbations, but without supporting documentation, is not sufficient to satisfy these inclusion criteria.
• ⚫ Examples of acceptable documentation of the asthma disease state and prior asthma exacerbations include clinic visit (primary or specialist Health care provider (HCP)), emergency room/urgent care, or hospital records listing asthma as a current problem, plus documentation of at least 1 asthma exacerbations during the 12 months prior to ICF.
• Weight
• 9. Weight of ≥40 kg.
• Sex and Contraceptive/Barrier Requirements
• 10. Male and/or female
• Contraceptive use by females should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
• • Female patients:
• • Females not of childbearing potential are defined as females who are either permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Females will be considered postmenopausal if they have been amenorrhoeic for 12 months prior to Visit 1(Week -1 to Week 0) without an alternative medical cause. The following age-specific requirements apply:
• • Females < 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatment and FSH levels in the postmenopausal range.
• • Females ≥ 50 years old would be considered postmenopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatment.
• • Female patients of childbearing potential must use one highly effective form of birth control. A highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly. Females of childbearing potential who are sexually active with a non-sterilised male partner must agree to use one highly effective method of birth control, as defined below, from enrolment throughout the study and until at least 12 weeks after last dose of study intervention. Cessation of contraception after this point should be discussed with a responsible physician.
• • The following are not acceptable methods of contraception: periodic abstinence (calendar, symptothermal, post-ovulation methods), withdrawal (coitus interruptus), spermicides only, and lactational amenorrhoea. Female condom and male condom should not be used together.
• • All WOCBP must have a negative serum pregnancy test result at Visit 1(Week -1 to Week 0).
• • Highly effective birth control methods include: Total sexual abstinence is an acceptable method provided it is the usual lifestyle of the patient (defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments) [(periodic abstinence eg, calendar, ovulation,symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to study intervention, and withdrawal are not acceptable methods of contraception], a vasectomised partner, Implanon®, bilateral tubal occlusion, intrauterine device/levonorgestrel intrauterine system, Depo-Provera™ injections, oral contraceptive, and Evra Patch™, Xulane™, or NuvaRing®.