A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of GB-0895 Adjunctive Therapy in Adults and Adolescents With Severe Uncontrolled Asthma
概览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 786
- 试验地点
- 28
- 主要终点
- To evaluate the annualized asthma exacerbation rate (AAER) in adult and adolescent subjects with severe uncontrolled asthma.
概览
简要总结
The objective of this study is to assess the potential for GB-0895 treatment to improve the health of adolescents and adults with severe asthma that is uncontrolled by inhaled corticosteroids (ICS) and conventional asthma controllers.
The study details include:
Study treatment: randomized to receive either GB-0895 or placebo administered every 6 months over 52 weeks.
Visit frequency: every 1-2 months after the first month.
详细描述
This is a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 study to evaluate the efficacy and safety of GB-0895 adjunctive therapy in adults and adolescents with severe uncontrolled asthma with an optional open-label extension (OLE). The trial is designed to administer GB-0895 an investigational drug or placebo, subcutaneously every 6 months.
The study is divided into several phases as described below:
- Screening/Baseline (Weeks -6 to -4)
- Run-in (Weeks -4 to 0, ±1)
- Treatment (Weeks 0 to 52)
- Follow-up (Weeks 52 to 90) or optional open-label extension (OLE) (Weeks 52 to 142, OLE includes GB-0895 treatment on Week 52 and Week 78)
Approximately 786 eligible study participants will be screened and randomized globally to receive either GB-0895 or placebo at week 0 and week 26. The safety of the participants enrolled in this trial will be carefully monitored.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 12 Years 至 80 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults and adolescents ≥ 12 and ≤ 80 years of age.
- •Documented physician diagnosis of asthma for ≥ 2 years.
- •Subjects must be on medium to high dose ICS for ≥ 12 months before Screening Visit 1 plus at least 1 additional asthma controller (e.g., LABA, LAMA) ≥ 3 months before Screening Visit 1 with no change in ICS or controller(s) for at least three months.
- •Subjects must have a well-documented history of at least two asthma exacerbations requiring systemic corticosteroid treatment despite the use of medium-to-high dose ICS in the past 12 months before Screening Visit
- •Adults ≥ 18 years of age at Screening Visit 1, a pre-BD FEV1 \<80% predicted at Screening Visit
- •Adolescents 12 to \< 18 years of age at Screening Visit 1: A pre-BD FEV1 \< 90% predicted OR, FEV1:Forced Vital Capacity (FVC) ratio \< 0.
- •Positive BD responsiveness test: Increase of at least 12% and 200 mL in FEV1 between 15 and 60 minutes after the administration of a short-acting β2-agonist (SABA) at least once during the screening period.
- •ACQ-6 score ≥ 1.5 at the Screening Visit.
- •Weight ≥40 kg at the Screening Visit 1
排除标准
- •Subjects who experience a clinically significant asthma exacerbation within 12 weeks before the Screening Visit or during the run-in period and require a change in asthma maintenance therapy.
- •Other concurrent respiratory disease other than asthma, including (but not limited to) current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, tuberculosis, diagnosis of chronic pulmonary disease (including but not limited to emphysema and/or chronic bronchitis), or a history of lung cancer.
- •Eosinophilic disease (e.g., eosinophilic granulomatosis with polyangiitis, eosinophilic esophagitis).
- •Any cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could affect subject safety, influence study findings or interpretation, or impede completion of the study.
- •Clinically significant infection that is unresolved and requires systemic antibiotic, antifungal, antiparasitic, or antiviral medications preceding enrollment.
- •A current malignancy or previous history of cancer within 5 years before screening.
- •Clinically significant infection that is not resolved before study enrollment.
- •Subjects with a known, pre-existing helminth parasitic infestation within 6 months before Screening Visit
- •Current smokers or subjects with a smoking history ≥10 pack-years, and subjects using vaping products, including electronic cigarettes.
- •Former smokers with a smoking history of \<10 pack-years and users of vaping/e-cigarette products must have stopped for at least 6 months before Screening Visit 1 to be eligible.
研究组 & 干预措施
Placebo
Placebo Subcutaneous (SC) injection
干预措施: Placebo (Drug)
GB-0895
GB-0895 Subcutaneous (SC) injection
干预措施: GB-0895 (Drug)
结局指标
主要结局
To evaluate the annualized asthma exacerbation rate (AAER) in adult and adolescent subjects with severe uncontrolled asthma.
时间窗: From Day 1 (randomization) to Week 52
The annual exacerbation rate is based on clinically significant (CS) exacerbations reported by the investigator in the electronic case (eCRF) over 52 weeks for subjects on GB-0895 as compared to placebo.
To evaluate the annualized asthma exacerbation rate (AAER) in adult and adolescent subjects with severe uncontrolled asthma.
时间窗: From Day 1 (randomization) to Week 52
The annual exacerbation rate is based on clinically significant (CS) exacerbations reported by the investigator in the electronic case (eCRF) over 52 weeks for subjects on GB-0895 as compared to placebo.
次要结局
- Change from baseline in Asthma Control Questionnaire (ACQ-6) score(From Day 1 (randomization) to Week 52)
- To evaluate the annualized asthma exacerbation rate (AAER) in adult and adolescent subjects with severe uncontrolled asthma and baseline eosinophils (EOS) < 300 cells/µL.(From Day 1 (randomization) to Week 52)
- Change from baseline in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1)(From Day 1 (randomization) to Study Week 52)
- Change from baseline in Asthma Quality of Life Questionnaire AQLQ(S)12+ score(From Day 1 (randomization) to Week 52)
- Time to first asthma exacerbation from randomization(From Day 1 (randomization) to Week 52)
- Change from baseline in weekly mean daily Asthma Daytime Symptom Diary (ADSD)(From Day 1 (randomization) to Week 52)
- Change from baseline in weekly mean daily Asthma Nighttime Symptom (ANSD)(From Day 1 (randomization) to Week 52)
- Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score(From Day 1 (randomization) to Week 52)
- Change from baseline in 22-Item Sino-Nasal Outcomes Test (SNOT-22) score(From Day 1 (randomization) to Week 52)
- Change from baseline in the 5-Level EuroQol 5 dimensions questionnaire (EQ-5D-5L) score(From Day 1 (randomization) to Week 52)
- PGI-S response at Week 52(From Day 1 (randomization) to Week 52)
- ACQ-6 response at Week 52(From Day 1 (randomization) to Week 52)
- AQLQ(S)12+ response at Week 52(From Day 1 (randomization) to Week 52)
- SGRQ response at Week 52(From Day 1 (randomization) to Week 52)
- To evaluate the annualized asthma exacerbation rate (AAER) in adult and adolescent subjects with severe uncontrolled asthma and baseline eosinophils (EOS) < 300 cells/µL.(From Day 1 (randomization) to Week 52)
- Change from baseline in pre-bronchodilator (BD) forced expiratory volume in 1 second (FEV1)(From Day 1 (randomization) to Study Week 52)
- Change from baseline in Asthma Quality of Life Questionnaire AQLQ(S)12+ score(From Day 1 (randomization) to Week 52)
- Change from baseline in Asthma Control Questionnaire (ACQ-6) score(From Day 1 (randomization) to Week 52)
- Time to first asthma exacerbation from randomization(From Day 1 (randomization) to Week 52)
- Change from baseline in weekly mean daily Asthma Daytime Symptom Diary (ADSD)(From Day 1 (randomization) to Week 52)
- Change from baseline in weekly mean daily Asthma Nighttime Symptom (ANSD)(From Day 1 (randomization) to Week 52)
- Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score(From Day 1 (randomization) to Week 52)
- Change from baseline in 22-Item Sino-Nasal Outcomes Test (SNOT-22) score(From Day 1 (randomization) to Week 52)
- Change from baseline in the 5-Level EuroQol 5 dimensions questionnaire (EQ-5D-5L) score(From Day 1 (randomization) to Week 52)
- PGI-S response at Week 52(From Day 1 (randomization) to Week 52)
- ACQ-6 response at Week 52(From Day 1 (randomization) to Week 52)
- AQLQ(S)12+ response at Week 52(From Day 1 (randomization) to Week 52)
- SGRQ response at Week 52(From Day 1 (randomization) to Week 52)