A Phase 2 Open-Label Extension Study to Evaluate the Safety and Pharmacodynamics of Belcesiran in Patients With PiZZ Alpha-1 Antitrypsin Deficiency Associated Liver Disease
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- The change from baseline in pulmonary function tests (PFTs)
研究概览
简要总结
This is a Phase 2, multicenter, open-label extension of Study DCR-A1AT-201, designed to evaluate the long-term safety and further characterize the pharmacodynamics (PD) of belcesiran in adult patients with PiZZ AATLD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Must be 18 to 75 years of age inclusive, at the time of signing the Informed Consent Form (ICF).
- •Documented diagnosis of PiZZ-type Alpha-1 Antitrypsin deficiency (AATD), confirmed by genotyping.
- •Lung, renal and liver function within acceptable limits.
- •Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
排除标准
- •Any condition that, in the opinion of the Investigator, would make the participant unsuitable for enrollment or could interfere with participation in or completion of the study
- •Routine use of acetaminophen/paracetamol
- •Use of systemically acting steroids in the month prior to Screening and throughout the study period.
- •Positive SARS-CoV-2 virus test at Screening
- •Any other safety laboratory test result considered clinically significant and unacceptable by the Investigator
- •Inability or unwillingness to comply with the specified study procedures, including lifestyle considerations
研究组 & 干预措施
belcesiran
Participants who completed the DCR-A1AT-201 treatment period will receive open-label belcesiran administered subcutaneously
干预措施: Belcesiran (Drug)
结局指标
主要结局
The change from baseline in pulmonary function tests (PFTs)
时间窗: up to 152 weeks
Forced expiratory volume in 1 second (FEV1)
The change from baseline in physical examination (PE) findings
时间窗: up to 56 weeks
body weight
The change from baseline in clinical laboratory tests: Clinical Chemistry
时间窗: up to 152 weeks
Clinical Chemistry is collected to evaluate the long-term safety of belcesiran
The change from baseline in PFTs
时间窗: up to 152 weeks
diffusing capacity for carbon monoxide (DLCO)
The incidence of treatment-emergent adverse events
时间窗: up to 152 weeks
The change from baseline in 12-lead electrocardiogram (ECG)
时间窗: up to 56 weeks
heart rate
The change from baseline in ECG
时间窗: up to 56 weeks
ventricular rate
The change from baseline in 12-lead ECG
时间窗: up to 56 weeks
corrected QT interval (QTcF, Fridericia correction)
The change from baseline in PE findings
时间窗: up to 56 weeks
physical examination to assess skin, lungs, cardiovascular system, and abdomen (liver and spleen) based on the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE; version 5.0) grading scale
The change from baseline in clinical laboratory tests: Hematology
时间窗: up to 152 weeks
Hematology is collected to evaluate the long-term safety of belcesiran
The change from baseline in clinical laboratory tests: Coagulation
时间窗: up to 152 weeks
Coagulation is collected to evaluate the long-term safety of belcesiran
The change from baseline in vital sign measurements
时间窗: up to 56 weeks
oral temperature
The change from baseline in clinical laboratory tests: Urinalysis
时间窗: up to 152 weeks
Urinalysis is collected to evaluate the long-term safety of belcesiran
次要结局
- Changes in serum AAT protein concentrations over time(up to 152 weeks)