A Randomized Double-blind Crossover Study to Assess the Safety and Pharmacokinetics of Two Different Doses of Weekly Intravenous Administration of Alpha1-Proteinase Inhibitor (Human) Prolastin®-C in Subjects With Alpha1-Antitrypsin Deficiency
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 10
- 主要终点
- Subjects With Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
This is a study to assess the safety and pharmacokinetics of weekly infusions of 120 mg/kg of Prolastin-C (alpha1-proteinase inhibitor [alpha1-PI] [Human]), compared to weekly infusions of 60 mg/kg of Prolastin-C in patients with alpha 1-antitrypsin deficiency (AATD).
详细描述
The question of whether higher doses of alpha1-PI (>60 mg/kg) are able to provide better protection to patients with alpha 1-antitrypsin deficiency is currently unknown. As a first step to address this question, the present study has been undertaken. This is a multi-center, randomized, double-blind, crossover study to assess the safety and pharmacokinetics of weekly infusions of 120 mg/kg of Prolastin-C, compared to weekly infusions of 60 mg/kg of Prolastin-C in patients with alpha 1-antitrypsin deficiency. This study is a crossover design with 2 treatment sequences:
Treatment Sequence 1: 60 mg/kg weekly infusion of Prolastin-C for 8 weeks followed by 120 mg/kg weekly infusion of Prolastin-C for 8 weeks (starting at Week 1) (total of 16 treatment weeks)
Treatment Sequence 2: 120 mg/kg weekly infusion of Prolastin-C for 8 weeks followed by 60 mg/kg weekly infusion of Prolastin-C for 8 weeks (starting at Week 11) (total of 16 treatment weeks)
Approximately 15 subjects are planned to be entered into each treatment sequence.
At Weeks 8 to 11 and Weeks 18 to 21, a total of 15 serial blood samples for each subject will be drawn for pharmacokinetic analysis. The expected duration of the study subject's participation will be approximately 25 weeks (which includes a 3-Week Screening Phase, 2-Week Washout Period [between different alpha-1 PI treatment doses], and a 4-Week Follow-up Period). The following safety parameters will be assessed: adverse events, pulmonary exacerbations, vital signs, pulmonary function tests, and clinical laboratory tests.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Be between 18 and 70 years of age
- •Have a documented diagnosis of congenital AATD
- •Have a post-bronchodilator Forced Expired Volume in 1 second (FEV1) of ≥30% and <80% and FEV1/forced vital capacity (FVC) <70%
- •If receiving alpha-1 PI augmentation therapy, be willing to discontinue the treatment for the duration of the study
排除标准
- •Had a moderate or severe pulmonary exacerbation during the 4 weeks before the study
- •History of lung or liver transplant
- •Any lung surgery during the past 2 years
- •Confirmed liver cirrhosis
- •Elevated liver enzymes
- •Severe concurrent disease
- •Females who are pregnant or breast-feeding or unwilling to practice effective contraception during the study
- •Infection with hepatitis A, B, or C, human immunodeficiency or parvovirus B19
- •Smoking during the past 6 months
- •Use of systemic steroids within 4 weeks of the study
- •Use of antibiotics for an exacerbation within 4 weeks of the study
结局指标
主要结局
Subjects With Treatment-Emergent Adverse Events (TEAEs)
时间窗: 22 weeks
Number of subjects experiencing at least one TEAE. TEAEs were defined as any adverse event (AE) during the study that began on or after the date of first dose of investigational product (i.e., Prolastin-C).
Subjects With Drug-Related TEAE(s)
时间窗: 22 weeks
Number of subjects with at least one TEAE that was determined by the Investigator to be either "possibly related" or "related" to the investigational product (i.e., Prolastin-C).
Subjects With Treatment-Emergent Serious Adverse Events (SAEs)
时间窗: 22 weeks
Number of subjects who experienced at least one treatment-emergent SAE.
Subjects Withdrawn Due to an AE(s)
时间窗: 22 weeks
Number of subjects who were withdrawn from the study due to at least one AE.
Subjects With Treatment-Emergent Pulmonary Exacerbation(s)
时间窗: 22 weeks
Number of subjects with at least one treatment-emergent pulmonary exacerbation
Subjects With Severe TEAE(s) or Pulmonary Exacerbation(s)
时间窗: 22 weeks
Number of subjects who experienced at least one severe TEAE or pulmonary exacerbation.
Number of TEAEs
时间窗: 22 Weeks
Total number of TEAEs reported.
Number of Drug-related TEAEs
时间窗: 22 Weeks
Total number of drug-related TEAEs reported
Number of Treatment-Emergent Pulmonary Exacerbations
时间窗: 22 Weeks
Total number of treatment-emergent pulmonary exacerbations.
次要结局
- AUC0-7days(Week 8 and Week 18 at the following timepoints: 0 (pre-infusion), completion of first infusion bag, completion of 2nd infusion bag, and 15 min, 30 min, and 1, 2, 4, 8, 24, 48, 120, and 168 hours post-dose)
- Mean Trough(Single measurment immediately prior to infusion at Weeks 6, 7, 8, 9 and Weeks 16, 17, 18, 19)