A Phase IIb Randomized, Double-blind, Placebo-controlled, Parallel, Multidose Study to Evaluate the Efficacy, Safety, and PK of AZD0292 in Participants 12 Years of Age and Older With Bronchiectasis and Chronic Pseudomonas Aeruginosa Colonization
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 435
- 试验地点
- 213
- 主要终点
- Annualized rate of exacerbations over a variable follow-up time
研究概览
简要总结
AZD0292 is a bispecific IgG1k mAb being evaluated for the prevention of exacerbations in bronchiectasis patients chronically colonized with PsA.
详细描述
AZD0292 is a bispecific IgG1k mAb being evaluated for the prevention of exacerbations in bronchiectasis patients chronically colonized with PsA.
This Phase IIb study aims to assess the efficacy, safety, and PK of 2 dosage regimens of AZD0292 administered IV, as compared to placebo in participants 12 years of age and older.
The primary population of this study will be PsA-colonized NCFBE patients, a bronchiectasis group with frequent pulmonary exacerbations due to chronic PsA airway colonization. These PsA associated pulmonary exacerbations contribute to a decline in lung function, impair quality of life and increase mortality, highlighting the urgent need for effective therapeutic options. To investigate the broader applicability of AZD0292, bronchiectasis patients with CF who are colonized with PsA will be also included as a non-powered exploratory group in this Phase IIb study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Participants, Investigators, site staff, and AstraZeneca study staff who are involved in the treatment or clinical evaluation and monitoring of the participants will remain blinded to each participant's treatment assignment throughout the course of the study. As AZD0292 and placebo are visually distinct prior to dose preparation, an unblinded pharmacist (or designee, in accordance with local and institutional regulations) will be responsible for the handling and dose preparation of all study intervention and will endeavor to ensure that there are no differences in time taken to dispense following randomization.
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant must be ≥ 12 years of age at the time of signing the informed consent/assent
- •Weight ≥ 35 kg
- •Bronchiectasis diagnosed by a physician and confirmed by CT demonstrating abnormal bronchial dilation in ≥ 1 lobe. Note: A historical CT scan within the past 5 years is acceptable. If not available, a CT scan should be conducted at screening to confirm eligibility.
- •Participants who are receiving appropriate standard of care therapy per local guidelines and have a documented history of ≥ 2 moderate exacerbations or ≥ 1 severe exacerbation in the preceding 12 months requiring antibiotics
- •Participants who are clinically stable and free from an exacerbation of bronchiectasis for 4 weeks prior to randomization
- •Participants with pre- or post-bronchodilator FEV1 ≥ 25% predicted value at screening.
- •Presence of positive (PCR or culture) PsA in an airway sample at least once in the last 24 months prior to screening
- •Presence of culture positive PsA in sputum at least within 5 weeks of randomization. Participants who have previously received PsA eradication therapy, as determined appropriate by their treating provider, but remain colonized with PsA are eligible for the study.
- •Capable of giving signed informed consent/assent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol
排除标准
- •Primary lung diagnosis other than bronchiectasis
- •Evidence of active tuberculosis or active nontuberculous mycobacteria being treated or requiring treatment. Participants currently receiving treatment for active TB or nontuberculous mycobacteria may be considered after completion of an appropriate course of therapy
- •Evidence of an active allergic bronchopulmonary aspergillosis being treated or requiring treatment
- •Need for long term supplemental oxygen. Oxygen use for ambulation and relief of breathlessness after exercise is allowed
- •Malignancy, current or within the previous 5 years, except for stable prostate cancer, adequately treated non-invasive basal cell and squamous cell carcinoma of the skin and cervical carcinoma in situ treated with apparent success more than one year prior to enrolment
- •AIDS or Advanced human immunodeficiency virus disease (CD4 count of < 200 cells/mm3)
- •History of severe adverse reaction associated with a mAb, and/or history of severe allergic reaction (eg, anaphylaxis that required the use of epinephrine/adrenaline or hospitalization), and/or history of immune complex disease (Type III hypersensitivity reactions) to monoclonal antibody administration
- •Treatment with long term anti-PsA antibiotics, macrolides, or DPP-1 inhibitors, which are newly initiated within the 3 months prior to screening
- •Chronic immunosuppressive therapy (including prednisolone > 5 mg or equivalent) newly initiated within the last 3 months
- •Receipt of investigational products indicated for the treatment or prevention of bronchiectasis exacerbations or expected receipt during the study
- •Participants with CF on CFTR modulator therapies which are newly initiated within the previous 3 months prior to screening
- •Female participants who are pregnant, lactating, or WOCBP and not using a highly effective method of contraception or abstinence from at least 4 weeks prior to study intervention administration and until at least 6 months after study intervention administration
研究组 & 干预措施
Low-dose
Low-dose AZD0292 administered starting on Day 1, subsequent administrations per schedule of assessments.
干预措施: AZD0292 (Biological)
Placebo
Placebo administered starting on Day 1, subsequent administrations per schedule of assessments.
干预措施: Placebo (Other)
High-dose
High-Dose AZD0292 administered starting on Day 1, subsequent administrations per schedule of assessments.
干预措施: AZD0292 (Biological)
结局指标
主要结局
Annualized rate of exacerbations over a variable follow-up time
时间窗: Min 28 weeks, max 52 weeks
To evaluate the effect of IV AZD0292 compared to placebo on the rate of moderate-to-severe pulmonary exacerbations in participants with NCFBE and chronic colonization with PsA.
Annualized rate of exacerbations over a variable follow-up time
时间窗: Min 28 weeks, max 52 weeks
To evaluate the effect of IV AZD0292 compared to placebo on the rate of moderate-to-severe pulmonary exacerbations in participants with NCFBE and chronic colonization with PsA.
次要结局
- Incidence of AEs, SAEs, AESIs and MAAEs(Occurrence of AEs; first dose through 12 weeks after last study intervention administration. Occurrence of SAEs, AESIs, and MAAEs; through study completion (Final Dose+24 weeks))
- Annualized rate of severe exacerbations over a variable follow-up time(Min 28 weeks, max 52 weeks)
- Change from baseline in QOL-B-RSS(Over the observation period (Week 0 to Final Dose+4 weeks))
- Change from baseline in SGRQ score(Over the observation period (Week 0 to Final Dose +4 weeks))
- Time to first moderate or severe exacerbation(Through study completion (Final Dose +24 weeks))
- Serum PK Concentrations(At specified timepoints between Week 0 and Final Dose+12 weeks)
- Incidence of ADA and ADA titers to AZD0292(At specified timepoints between Week 0 and Final Dose +12 weeks)
- Annualized rate of severe exacerbations over a variable follow-up time(Min 28 weeks, max 52 weeks)
- Change from baseline in QOL-B-RSS(Over the observation period (Week 0 to Final Dose+4 weeks))
- Change from baseline in SGRQ score(Over the observation period (Week 0 to Final Dose +4 weeks))
- Time to first moderate or severe exacerbation(Through study completion (Final Dose +24 weeks))
- Serum PK Concentrations(At specified timepoints between Week 0 and Final Dose+12 weeks)
- Incidence of ADA and ADA titers to AZD0292(At specified timepoints between Week 0 and Final Dose +12 weeks)
- Incidence of AEs, SAEs, AESIs and MAAEs(Occurrence of AEs; first dose through 12 weeks after last study intervention administration. Occurrence of SAEs, AESIs, and MAAEs; through study completion (Final Dose+24 weeks))