A Multi-Center, Open-Label Study to Evaluate the Long-term Safety of Weekly Intravenous Infusions of Alpha1-Proteinase Inhibitor (Human) in Japanese Subjects With Alpha1 Antitrypsin Deficiency
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 4
- 试验地点
- 6
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
This is a multi-center, open-label study to evaluate the long-term safety of weekly intravenous (IV) infusions of 60 mg/kg alpha1-PI (human), modified process (Alpha-1 MP) in adult participants with Alpha1 Antitrypsin Deficiency (AATD) in Japan who have completed Study GTI1401 (NCT02870309).
详细描述
This is a multi-center, open-label study to evaluate the long-term safety of weekly IV infusions of 60 mg/kg Alpha-1 MP in adult participants with AATD in Japan who have completed Study GTI1401. Study GTI1401 is being conducted to evaluate the safety and pharmacokinetics (PK) of Alpha-1 MP in participants with AATD in Japan. In the current study, GTI1401-OLE, participants will be administered 60 mg/kg Alpha-1 MP by weekly IV infusion for approximately 1 year (can be renewed annually with the consent of the participants unless the sponsor informs of discontinuation of this OLE trial) to assess the long-term safety of Alpha-1 MP in participants with AATD. This study will be conducted at up to 5 centers in Japan.
At the Week 9 Visit of Study GTI1401, after giving consent, on the same day, participants will be assessed for eligibility at Screening/Extension (Ext) Week 1 Visit for this extension study, Study GTI1401-OLE. If eligible, participants will be administered weekly IV infusions of 60 mg/kg Alpha-1 MP for approximately 1 year or longer. The Week 9 Visit of GTI1401 will be the End of Study Visit for the participants who are enrolled in Study GTI1401-OLE.
Participants in Study GTI1401-OLE will have the option to remain in Study GTI1401-OLE and continue to receive weekly IV infusions of 60 mg/kg Alpha-1 MP for another year or longer. If participants plan to conclude their participation in the study (GTI1401-OLE) early (before Ext. Week 52), participants will be asked to complete the End of Study Follow-Up Assessments, which will be scheduled 4 weeks after the last infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects who complete participation in Study GTI1401 (i.e., have completed the study through the Week 9 Visit).
- •Subjects who will and are able to provide written informed consent.
排除标准
- •Subjects with newly diagnosed severe concomitant disease including, but not limited to, congestive heart failure and liver cirrhosis.
- •Subjects with newly diagnosed malignant tumor (including malignant melanoma; however, other forms of skin cancer are allowed).
- •Female subjects who are pregnant, breastfeeding or, if of child-bearing potential, unwilling to practice a highly effective method of contraception (oral, injectable or implanted hormonal methods of contraception, placement of an intrauterine device (IUD) or intrauterine system (IUS), condom or occlusive cap with spermicidal foam/gel/film/cream/suppository, male sterilization, or abstinence) throughout the study or male subjects who have a partner who is of child-bearing potential and is unwilling to practice a highly effective method of contraception throughout the study.
- •Subjects with clinical signs and symptoms of active hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) viral infection at the Week 9 Visit of Study GTI1401 and viral infection is further confirmed by testing.
- •Subjects with current evidence of smoking or has a positive urine cotinine test at the Week 9 Visit in Study GTI1401 that is due to smoking.
- •Subjects who currently participate in a study of another investigational product (other than Alpha-1 MP).
- •Subjects who have difficulty in adhering to the protocol or its procedures, in the opinion of the investigator.
- •Subjects who have medical conditions that may confound the results of this clinical trial or may endanger these subjects during their participation in this clinical trial in the opinion of the investigator.
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a medicinal product or study treatment and which did not necessarily have a causal relationship with this administration. TEAEs were defined as any AE occurring after or on the first Alpha-1 MP infusion until the final visit of study.
Number of Participants With Adverse Drug Reaction (ADRs)
时间窗: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
ADRs were defined as all noxious and unintended responses to a medicinal product or study treatment related to any dose. An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a medicinal product or study treatment and which did not necessarily have a causal relationship with this administration.
Number of Participants With Serious Adverse Events (SAEs)
时间窗: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
An AE was considered serious in any of the following outcomes or deemed significant for any other reason: death; life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; congenital anomaly/birth defect.
Number of Participants With Discontinuations Due to Adverse Events (AEs) or Serious Adverse Events (SAEs)
时间窗: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
An AE was defined as any untoward medical occurrence in a participant or clinical investigation participant administered a medicinal product or study treatment and which did not necessarily have a causal relationship with this administration. An AE was considered serious in any of the following outcomes or deemed significant for any other reason: death; life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; congenital anomaly/birth defect.
Number of Participants With Chronic Obstructive Pulmonary Disease (COPD) Exacerbations
时间窗: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
COPD exacerbation was defined as an increase in respiratory symptoms (dyspnea, increased cough, and/or production of sputum) over baseline that usually requires medical intervention.
Number of Participants With Clinically Significant Findings in Vital Signs
时间窗: From start of study drug administration through 30 days after last study drug infusion (Up to 228 weeks)
Vital signs included analysis of heart rate, blood pressure, respiratory rate, and temperature. Clinically significant findings in vital signs were based on investigator's discretion.
Number of Participants With Clinically Significant Findings in Clinical Laboratory Parameters
时间窗: Extension (Ext) Weeks 26, 52, 78, 104, 130, 156,182, 208 (prior to study drug administration) until end of study (Up to 228 weeks)
Clinical laboratory parameters included analysis of hematology, blood chemistry, and urinalysis. Clinically significant findings in clinical laboratory parameters were based on investigator's discretion.
Number of Participants With Clinically Significant Findings in Pulmonary Function Tests (PFTs)
时间窗: Extension (Ext) Weeks 26, 52, 78, 104, 130, 156,182, 208 (prior to study drug administration) until end of study (Up to 228 weeks)
Pulmonary function tests were measured by spirometry. It included Forced Expired Volume in 1 second (FEV1), Forced Vital Capacity (FVC), which were performed according to American Thoracic Society/ European Respiratory Society (ATS/ERS) guidelines. FEV1 is the amount of air which can be forcibly exhaled from the lungs in the first second of a forced exhalation. FVC is the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. PFTs were performed before infusion both pre- and post-bronchodilator administration. The post-bronchodilator PFT was performed 15 to 30 minutes after bronchodilator administration. The same bronchodilator was used throughout the study. Clinically significant findings in pulmonary function tests were based on investigator's discretion.
Trough Levels of Alpha1- Proteinase Inhibitor
时间窗: Extension (Ext) Weeks 12, 24, 36, 48, 64, 76, 88, 100, 116, 128, 140, 152, 168, 180, 192, 204 (prior to study drug administration) until end of study (Up to 228 weeks)
Alpha1-PI level was measured by nephelometry.
次要结局
未报告次要终点