A Phase 3, Open-Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Fazirsiran in Participants With Alpha-1 Antitrypsin Deficiency-Associated Liver Disease
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 18
- 试验地点
- 3
- 主要终点
- The primary safety endpoints for this study to be assessed over time and through the end of study (EOS) are: •AEs and SAEs including any pulmonary AEs or SAEs indicative of worsening pulmonarycondition or function (for example, pulmonary exacerbation, respiratory infection, significant pulmonary function test [PFT] decline.)
研究概览
简要总结
The primary objective of the study is to evaluate the safety and tolerability of the long-term treatment of fazirsiran in participants with AATD-LD.
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Safety Follow-Up Period
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 是
入选标准
- •The participant enrolling in this OLE study will have participated in a previously qualifying study, and will be considered for eligibility based on the following study-specific criteria: -AROAAT2001: – Participants with fibrosis may roll over into this OLE study after they reach their next regularly scheduled, Q12W visit. – Participants with fibrosis who have completed the AROAAT2001 study may be enrolled into the OLE study. -AROAAT2002: – Participants in Cohorts 1 and 1b may roll over after completing the 24 week primary study period. –Participants in Cohort 2 may roll over after completing the 48 week primary study period. – Participants who have completed the study may be enrolled into the OLE study. Note: If the first dose of fazirsiran in the OLE study will be delayed by more than 24 weeks after the last dose in AROAAT2001 or AROAAT2002, the rollover should be discussed with the medical monitor.
排除标准
- •The participant is likely to require major surgery. Major surgery typically requires at least 1 night in the hospital. Examples include laparoscopic surgery (except cholecystectomy and tubal ligation); GI tract surgery including 1 or more segments of the colon or terminal ileum; open resection of organs; large joint replacements; mastectomy with reconstruction; and spine, thoracic, vascular, or intracranial surgery. Note: participants who are awaiting a liver transplant may roll over into this study and receive treatment until the last regularly scheduled study visit, or 4 weeks before the procedure, whichever occurs later. In an urgent situation, a transplant should not be withheld due to timing of last dose.
- •The participant has evidence of other forms of chronic liver diseases, including viral hepatitis B or C, primary biliary cholangitis, primary sclerosing cholangitis, Wilson disease, alcoholic hepatitis, hemochromatosis, liver cancer, history of biliary diversion, or autoimmune hepatitis.
- •The participant has abnormal finding(s) of clinical relevance during the evaluation before the first study dosing that, in the opinion of the investigator, could adversely impact participant safety during the study or adversely impact study results.
- •The participant had major protocol deviation(s) (as determined by the sponsor) in AROAAT2001 or AROAAT2002 that would affect the conduct of this study.
- •The participant permanently discontinued investigational product because of an AE, adjudicated as related to the study intervention, in AROAAT2001 or AROAAT
- •Female participants who became pregnant during Study AROAAT2001 or AROAAT2002, female participants who are lactating or planning to become pregnant during the study period; or males or female participants of childbearing potential not agreeing to continue using appropriate contraception methods (that is, highly effective methods for female and medically appropriate methods for male study participants) through the conclusion of study participation.
结局指标
主要结局
The primary safety endpoints for this study to be assessed over time and through the end of study (EOS) are: •AEs and SAEs including any pulmonary AEs or SAEs indicative of worsening pulmonarycondition or function (for example, pulmonary exacerbation, respiratory infection, significant pulmonary function test [PFT] decline.)
The primary safety endpoints for this study to be assessed over time and through the end of study (EOS) are: •AEs and SAEs including any pulmonary AEs or SAEs indicative of worsening pulmonarycondition or function (for example, pulmonary exacerbation, respiratory infection, significant pulmonary function test [PFT] decline.)
•Change from baseline in pulmonary function parameters: – FEV1 (L) and percent predicted forced expiratory volume in the first second of expiration (ppFEV1 [%]). – FVC; L and percent predicted FVC (ppFVC; %). – FEV1/FVC ratio. – Diffusing capacity of lung for carbon monoxide (DLCO; mL/min/mm Hg) and percent predicted DLCO (ppDLCO; %). – DLCOhgb; mL/min/mm Hg and percent predicted DLCOhgb (ppDLCOhgb; %).
•Change from baseline in pulmonary function parameters: – FEV1 (L) and percent predicted forced expiratory volume in the first second of expiration (ppFEV1 [%]). – FVC; L and percent predicted FVC (ppFVC; %). – FEV1/FVC ratio. – Diffusing capacity of lung for carbon monoxide (DLCO; mL/min/mm Hg) and percent predicted DLCO (ppDLCO; %). – DLCOhgb; mL/min/mm Hg and percent predicted DLCOhgb (ppDLCOhgb; %).
Translation PT
Translation PT
•Vital signs.
•Vital signs.
•Change from baseline in clinical laboratory values (hematology, biochemistry including liver tests, coagulation, and urinalysis results).
•Change from baseline in clinical laboratory values (hematology, biochemistry including liver tests, coagulation, and urinalysis results).
次要结局
- •No progression from baseline of at least 1 stage of histologic fibrosis (by METAVIR staging) on liver biopsy at Week 102 (Yes/No)
- •In participants with baseline fibrosis of F1 or higher, a decrease from baseline of at least 1 stage of histologic fibrosis (by METAVIR staging) on liver biopsy at Week 102 (Yes/No)
- •Change from baseline in intrahepatic Z-AAT protein polymer burden assessed by periodic acid Schiff plus diastase (PAS+D) staining in liver biopsy at Week 102.
- •Change from baseline in intrahepatic portal inflammation in Week 102 liver biopsy.
- •Change from baseline in liver stiffness assessed by magnetic resonance elastography (MRE) (at select sites).
- •Change from baseline in liver stiffness assessed by vibration-controlled transient elastography (VCTE).
研究者
Takeda
Scientific
Takeda Development Center Americas Inc.