Severe Eosinophilic Asthma
Conditions
Brief summary
This is a prospective, multi-center, single-arm Phase 3b study designed to evaluate the potential benefit to patients if benralizumab treatment could enable reduction in asthma maintenance controllers while allowing patients to maintain asthma control in Chinese patients.
Detailed description
The study population will be approximately 440-520 patients on MD/HD ICS/LABA with and without LTRA or LAMA or theophylline and meeting study inclusion and exclusion criteria in China. After patients sign the informed consent, they will undergo a screening visit (Visit 1, Week -1 to Week 0) to assess eligibility criteria. Patients who meet eligibility criteria and complete study baseline assessments will enter the study and receive the first dose of benralizumab at visit 2 (Week 0). The benralizumab treatment includes 4 phases: Induction Phase (16 weeks), Reduction Phase (24 weeks), Maintenance Phase (16 weeks) and Follow-up Phase (4 weeks). After initiation of benralizumab 30 mg administered subcutaneously every 4 weeks (Q4W) for the first 3 doses (Visits 2 to 4), then every 8 weeks (Q8W) thereafter.
Interventions
DRUGBenralizumab
Severe eosinophilic asthma taking medium-high dose ICS/LABA with/without LTRAs, LAMAs will be enrolled into this single arm treatment.
Sponsors
AstraZeneca
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 75 Years
Healthy volunteers
No
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 * The documentation requirements for demonstrating pulmonary function reversibility are as follows for Screening (Visit 1, Week -1 to Week 0): 1. For patients diagnosed with asthma ≥1 year prior to enrolment, pulmonary function reports from within 12 months prior to Visit 1 are required: i. If pre- or post-bronchodilator FEV1/FVC ≥70% in reports within 12 months prior to Visit 1: Only objective records of prior reversibility testing confirming asthma diagnosis are required. ii. If both pre- and post-bronchodilator FEV1/FVC \<70% in reports within 12 months prior to Visit 1: Must provide objective documentation within 12 months prior to Visit 1 of any of the following: * Positive bronchodilator response test, or * Positive bronchial provocation test, or * Positive PEF diurnal variability (≥10% for adults, ≥13% for children), or * PEF improvement ≥20% post-bronchodilator, or * Post-treatment FEV1 improvement ≥12% and ≥200mL after 4 weeks of therapy within 12 months prior to Visit 1, or * Documented FEV1 variability ≥12% and ≥200mL between two stable visits (non-acute, non-infectious states). 2. For patients diagnosed with bronchial asthma \<1 year prior to enrollment: Require submission of objective documentation within 12 months prior to Visit 1 of any of the above reversibility criteria. 3. For all enrolled patients meeting inclusion/
Exclusion criteria
Bronchodilator testing will be conducted during the screening period to establish baseline data for further analysis. * 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®.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To assess the potential for benralizumab treated patients to reduce their standard of care asthma controller regimen in the overall patient populationa and by subgroups of baseline background therapy | within 40 weeks after the first administration | Main outcomes: Proportion of patients with at least one controller medication category reduction at end of reduction phase * discontinuation of LTRA, or * discontinuation of LAMA, or * getting to MD ICS/LABA or * getting to LD ICS/LABA Supportive outcomes: * Proportion of patients with individual category reduction at end of reduction phase * Proportion of patients with ≥2 category reductions in controller medication * In sub-group of patients who meet reduction criteria * proportion of patients with at least one controller medication category reduction, * proportion of patients with individual category reduction * proportion of patients with ≥2 reductions in controller medication at end of reduction phase |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To assess standard asthma efficacy measures for benralizumab treated patients when reducing their standard of care asthma controller regimen in the overall patient population a and by subgroups of baseline background therapy | From 16~40 weeks | * Change in pre-BD FEV1 from beginning of reduction phase to end of reduction phase * Change in ACQ-5 and SGRQ from beginning of reduction phase to end of reduction phase * Proportion of patients with no deterioration (defined as ACQ-5 change \<0.5 since last visit and FEV1 \< -100mL compared to beginning of reduction phase) during reduction phase |
| To assess if reductions in background therapies achieved at end of reduction phase aremaintained until end of maintenance phase in the overall patient population a and by subgroups of baseline background therapy | From 32-56 weeks | •Proportion of patients at the end of the maintenance phase who use the same background therapy that they achieved at the end of the reduction phase |
| To assess standard asthma efficacy measures for benralizumab treated patients at induction phase in the overall patient population and by subgroups of baseline background therapy | from 0-16 weeks | * Change in FEV1 from beginning of induction phase to end of induction phase * Change in ACQ-5 and SGRQ from beginning of induction phase to end of induction phase * Proportion of patients achieving ACQ-5 MCID improvement (defined as change in ACQ-5 ≤-0.5 compared to beginning of induction phase) and SGRQ MCID improvement (defined as change in SGRQ ≤-4 compared to beginning of induction phase) during induction phase |
| To assess overall asthma exacerbation rate during the study of severe eosinophilic asthma patients treated with benralizumab in the overall patient population and by subgroups of baseline background therapy | within 56 weeks after first administration | * Annualized asthma exacerbation rate during the study (from first dose to EOT) and 1-year baseline period * Change in annualized asthma exacerbation rate during study phase vs. 1-year baseline period Annualized asthma exacerbation rate Defined as Number of exacerbations×365.25/(Follow-Up Date-First Benralizumab dose date+1) |
| To assess biomarkers of severe eosinophilic asthma patients treated with benralizumab in the overall patient population and by subgroups of baseline background therapy | from -1 week to 56 week | Baseline and follow-up visits, and change from baseline: * Blood EOS * FeNO * Total IgE |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORMin Zhang, Professor
ShangHai First General Hospital
PRINCIPAL_INVESTIGATORHuaHao Shen, Professor
Second Affiliated Hospital, Zhejiang University, School of Medicine
Outcome results
None listed