Open Label Extension Study to Evaluate the Long-Term Safety and Efficacy of Pegunigalsidase Alfa (PRX-102) in Patients With Fabry Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 97
- 试验地点
- 30
- 主要终点
- Number of Participants With Treatment-related Adverse Events
研究概览
简要总结
The objective of CLI-06657AA1-04 (formerly PB-102-F60) was to evaluate the long-term safety, tolerability, and efficacy parameters of 1 mg/kg pegunigalsidase alfa administered intravenously every other week in adult Fabry patients who had successfully completed studies PB-102-F20, PB-102-F30, or at least 48 months in study PB-102-F03.
详细描述
This was an open-label study. Participants were enrolled to receive 1 mg/kg pegunigalsidase alfa as intravenous infusions every 2 weeks (±3 days). The duration of treatment was until pegunigalsidase alfa was commercially available to the participant, or at the discretion of the Sponsor. Efficacy and safety analyses were summarized using descriptive statistics for continuous variables and counts and percentages for categorical variables. Data from the parent studies were also included in the analyses.
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
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Completion of study PB-102-F20, study PB-102-F30, or at least 48 months in study PB-102-F
- •The participant signed informed consent.
- •Female participants and male participants whose co-partners were of child-bearing potential agreed to use a medically acceptable method of contraception. These included combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, or transdermal) supplemented with a barrier method (preferably male condom), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, or implantable) supplemented with a barrier method (preferably male condom), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, or sexual abstinence. Contraception had to be used for 2 weeks after treatment termination.
排除标准
- •Presence of any medical, emotional, behavioral, or psychological condition that, in the judgment of the Investigator, would interfere with patient compliance with the requirements of the study.
研究组 & 干预措施
Experimental open label
pegunigalsidase alfa
干预措施: pegunigalsidase alfa (Drug)
结局指标
主要结局
Number of Participants With Treatment-related Adverse Events
时间窗: From first ever infusion of pegunigalsidase alfa, which could have been in the parent study (PB-102-F01/F20/F30) or this extension study, CLI-06657AA1-04, until 90 days after the final dose visit for each participant. Mean individual exposure: 5.5 years
No primary or secondary endpoints were specified for this trial. Evaluation of safety was a main objective. A treatment-emergent adverse event (TEAE) was defined as any adverse event (AE) occurring after the start of study treatment and within the time of residual drug effect (20 days after last administration of study treatment) or a pre-treatment AE or medical condition that worsened in severity after the start of study treatment and within the time of residual drug effect. Each TEAE was classified for severity based on the Common Terminology Criteria for Adverse Events (CTCAE) v4.03 and for causality in the categories unrelated, unlikely, possible, probable and definitely. Treatment-related AEs were TEAEs with causality assessed as possible, probable or definitely related to study treatment. TEAEs were coded using the Medical Dictionary for Regulatory Activities (MedDRA) version (v)19.0. Related TEAEs reported in ≥2 percent of participants by Preferred Term are reported.
次要结局
- Change From Baseline to the Last Observation for the eGFR(From baseline (assessment before first exposure to study drug, which could have been in the parent study, PB-102-F01/F20/F30, or CLI-06657AA1-04) to last observation (last non-missing assessment; Mean(SD) exposure: 5.5 (1.96) years; range:1.3;10.6 years))
- Annualized eGFR Slope(From first ever infusion of pegunigalsidase alfa (which could have been in the parent study, PB-102-F01/F20/F30, or this extension study, CLI-06657AA1-04), until the end of the extension study; mean individual exposure: 5.5 years)
- Shift From Baseline to the Last Scheduled Visit in UPCR Category(Shift from baseline (assessment before first exposure to study drug which could be in the parent study PB-102-F01/F02/F30 or CLI-06657AA1-04) to last observation (last non-missing assessment; Mean(SD) exposure: 5.5 (1.96) years; range:1.3;10.6 years))
- Change From Baseline to the Last Observation in Plasma Lyso-Gb3 and Globotriaosylceramide (Gb3) Concentrations(Change from baseline (assessment before first exposure to study drug, which could be in the parent study, PB-102-F01/F20/F30, or CLI-06657AA1-04 ) to last observation (last non-missing assessment; Mean(SD) exposure: 5.5 (1.96) years; range:1.3;10.6 years))
- Change From Baseline to the Last Observation for Pain Severity Items of the Brief Pain Inventory (BPI)(Change from baseline (assessment before first exposure to study drug, which could be in the parent study, PB-102-F01/F20/F30, or CLI-06657AA1-04) to last observation (last non-missing assessment; Mean(SD) exposure: 5.5 (1.96) years; range:1.3;10.6 years))
- Change From Baseline to the Last Observation in Overall Score for the Mainz Severity Score Index (MSSI)(Change from baseline (assessment before first exposure to study drug, which could be in the parent study, PB-102-F01/F20/F30, or CLI-06657AA1-04) to last observation (last non-missing assessment; Mean(SD) exposure: 5.5 (1.96) years; range:1.3;10.6 years))
- Change in Use of Pain Medication During Treatment(Shift from baseline (assessment before first exposure to study drug, which could be in the parent study, PB-102-F01/F20/F30, or CLI-06657AA1-04) to 72 months, in number of participants using pain medications (categorized by 0, 1 and 2+ pain medications))
- Change From Baseline to the Last Observation in the EuroQoL Visual Analog Scale (EQ VAS) Score(Change from baseline (assessment before first exposure to study drug, which could be in the parent study, PB-102-F01/F20/F30, or CLI-06657AA1-04) to last observation (last non-missing assessment; Mean(SD) exposure: 5.5 (1.96) years; range:1.3;10.6 years))
- Change From Baseline to the Last Observation in Left Ventricular Mass Index(Change from baseline (assessment before first exposure to study drug, which could be in the parent study, PB-102-F01/F20/F30, or CLI-06657AA1-04) to last observation (last non-missing assessment; Mean(SD) exposure: 5.5 (1.96) years; range:1.3;10.6 years))
- Change in Infusion Premedication Use From Baseline to 12 Months(Baseline (assessment before fist exposure to study drug, which could be in the parent study, PB-102-F01/F20/F30, or this extension study, CLI-06657AA1-04) to 12 months)
- Change in Infusion Premedication Use From Baseline to 24 Months(Baseline (assessment before first exposure to study drug, which could have been in the parent study, PB-102-F01/F20/F30 or this extension study, CLI-06657AA1-04) to 24 months)
- Change in Infusion Premedication Use From Baseline to 48 Months(Baseline (assessment before first exposure to study drug, which could have been in the parent study, PB-102-F01/F20/F30 or this extension study, CLI-06657AA1-04) to 48 months)
- Change in Infusion Premedication Use From Baseline to 72 Months(Baseline (assessment before first exposure to study drug, which could have been in the parent study, PB-102-F01/F20/F30 or this extension study, CLI-06657AA1-04) to 72 months)
- Number of Participants Who Had ADA at Any Post-baseline Visit(From first ever infusion of pegunigalsidase alfa (which could have been in the parent study, PB-102-F01/F20/F30, or in this extension study, CLI-06657AA1-04), until the end of the study. Mean individual exposure was 5.5 years.)
- Number of Participants With Treatment-emergent ADA Who Had Titer-boosted or Treatment-induced ADA(From first ever infusion of pegunigalsidase alfa (which could have been in the parent study, PB-102-F01/F20/F30, or in this extension study, CLI-06657AA1-04), until the end of the study. Mean individual exposure was 5.5 years.)
- Infusion-related Reactions (IRRs) Occurring During the Infusion or Within 2 Hours After Its Completion (IRR-2H) in More Than One Participant Overall by MedDRA Preferred Term (PT)(From first ever infusion of pegunigalsidase alfa (which could have been in the parent study, PB-102-F01/F20/F30, or in this extension study, CLI-06657AA1-04), until the end of the study. Mean individual exposure was 5.5 years.)
- Infusion-related Reactions Occurring During the Infusion or Within 24H After Its Completion (IRR-24H) in More Than One Participant Overall by MedDRA PT(From first ever infusion of pegunigalsidase alfa (which could have been in the parent study, PB-102-F01/F20/F30, or in this extension study, CLI-06657AA1-04), until the end of the study. Mean individual exposure was 5.5 years.)