Clinical trial NCT06465485: STEP: Phase IIIb Study of Benralizumab to Step-down Maintenance Therapy in Patients With Severe Eosinophilic Asthma
Official title: STEP: A Prospective, Interventional, Multicenter, Single-Arm Phase 3b Study to Evaluate the Step-Down of Maintenance Therapy in Patients With Severe Eosinophilic Asthma Treated With Benralizumab
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Severe Eosinophilic Asthma
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2024-06-18
Enrollment: 476
Sex: ALL
Minimum age (years): 12
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 480 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.

Eligibility 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.

  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®.

Primary outcomes:
measure: To assess the potential for benralizumab treated patients to reduce their standard of care asthma controller regimen in the overall patient population and by subgroups of baseline background therapy Subgroups of background therapy
timeFrame: within 40 weeks after the first administration
Secondary outcomes:
measure: To assess standard asthma efficacy measures for benralizumab treated patients when reducing their standard of care asthma controller regimen for pulmonary function measured by pre-BD FEV1
timeFrame: From 16~40 weeks
measure: To assess standard asthma efficacy measures for benralizumab treated patients when reducing their standard of care asthma controller regimen for asthma symptoms control measured by ACQ-5 & SGRQ Score
timeFrame: From 16~40 weeks
measure: 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
timeFrame: from 0-16 weeks
measure: 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
timeFrame: within 0-16 weeks after first administration
measure: 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
timeFrame: within 56 weeks after first administration
measure: To assess biomarkers of severe eosinophilic asthma patients treated with benralizumab in the overall patient population and by subgroups of baseline background therapy
timeFrame: from -1 week to 60 week
measure: To assess biomarkers of severe eosinophilic asthma patients treated with benralizumab in the overall patient population and by subgroups of baseline background therapy
timeFrame: from -1 week to 56 week
measure: To assess the safety and tolerability of benralizumab during the study in patients with severe eosinophilic asthma, while reducing their standard of care asthma controller regimen and maintaining asthma symptom control.
timeFrame: from -1 week to 60 week
measure: To assess biomarkers of severe eosinophilic asthma patients treated with benralizumab in the overall patient population and by subgroups of baseline background therapy
timeFrame: from -1 week to 56 week
Other outcomes:
Locations:
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Beijing
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Changsha
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chengdu
country: China
facility: Research Site
city: Chongqing
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guangzhou
country: China
facility: Research Site
city: Guilin
country: China
facility: Research Site
city: Guiyang
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hangzhou
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Hefei
country: China
facility: Research Site
city: Hohhot
country: China
facility: Research Site
city: Hohhot
country: China
facility: Research Site
city: Huzhou
country: China
facility: Research Site
city: Jinan
country: China
facility: Research Site
city: Jinan
country: China
facility: Research Site
city: Jinan
country: China
facility: Research Site
city: Kunming
country: China
facility: Research Site
city: Lanzhou
country: China
facility: Research Site
city: Lanzhou
country: China
facility: Research Site
city: Luoyang
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Nanjing
country: China
facility: Research Site
city: Nanning
country: China
facility: Research Site
city: Ningbo
country: China
facility: Research Site
city: Qingdao
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shanghai
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Shenyang
country: China
facility: Research Site
city: Shenzhen
country: China
facility: Research Site
city: Shenzhen
country: China
facility: Research Site
city: Shenzhen
country: China
facility: Research Site
city: Shenzhen
country: China
facility: Research Site
city: Shijiazhuang
country: China
facility: Research Site
city: Shijiazhuang
country: China
facility: Research Site
city: Suzhou
country: China
facility: Research Site
city: Suzhou
country: China
facility: Research Site
city: Taiyuan
country: China
facility: Research Site
city: Taiyuan
country: China
facility: Research Site
city: Tangshan
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: Tianjin
country: China
facility: Research Site
city: WeiFang
country: China
facility: Research Site
city: Wenzhou
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhan
country: China
facility: Research Site
city: Wuhu
country: China
facility: Research Site
city: Xi'an
country: China
facility: Research Site
city: Xi'An
country: China
facility: Research Site
city: Xiamen
country: China
facility: Research Site
city: Xian
country: China
facility: Research Site
city: Xinxiang
country: China
facility: Research Site
city: Xuzhou
country: China
facility: Research Site
city: Yangzhou
country: China
facility: Research Site
city: Zhangzhou
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
city: Zhengzhou
country: China
facility: Research Site
Study officials:
affiliation: ShangHai First General Hospital
name: Min Zhang, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Second Affiliated Hospital, School of Medicine, Zhejiang University
name: HuaHao Shen, Professor
role: PRINCIPAL_INVESTIGATOR
References: