A Multicenter Open-Label Treatment Protocol to Observe the Safety of Replagal® (Agalsidase Alfa) Enzyme Replacement Therapy in Canadian Patients With Fabry Disease
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 171
- 试验地点
- 24
- 主要终点
- Number of Participants With Infusion-Related Reactions (IRR)
研究概览
简要总结
The purpose of this study is to observe the safety of agalsidase alfa in Canadian patients with Fabry disease.
详细描述
This study will evaluate the safety of agalsidase alfa in patients with Fabry disease.
Patients diagnosed with Fabry disease who meet current Canadian guidelines for enzyme replacement therapy will be eligible to enroll in the study and will receive agalsidase alfa at a dose of 0.2 mg/kg body weight administered by an IV infusion over 40 minutes every week or every other week, based on previous treatment.
Shire has implemented a change to the drug substance manufacturing process. Safety data will be collected in patients receiving product manufactured with this process. There are no changes to the drug product formulation, manufacturing site, manufacturing process, and container closure.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient has a documented diagnosis of Fabry disease.
- •The patient is sufficiently compliant with study activities to participate in this treatment plan, as judged by the Investigator.
- •The patient must meet current Canadian guidelines for enzyme replacement therapy for Fabry disease by meeting one of the following criteria:
- •Age-adjusted glomerular filtration rate (GFR) <80 ml/min or a decline in GFR of >10% which is sustained for 3 months and for which other causes of declining renal function have been excluded by a nephrologist or any 2 of the following:
- •Isolated proteinuria ≥500 mg/day/1.73 m2 without other cause
- •Nephrogenic diabetes insipidus
- •Fanconi syndrome
- •Hypertension
- •Evidence of cardiac involvement related to Fabry disease including any 2 of the following:
- •Left ventricular (LV) wall thickness >12 mm
- •Left ventricular hypertrophy (LVH) by electrocardiogram (ECG); Estes ECG score must be >5
- •Left ventricular mass index (LVMI) by 2D echocardiogram 20% above normal for age
- •Diastolic filling abnormalities by 2D echocardiogram or by other accepted measures of diastolic filling. E/A ration >2.0 and deceleration time <140 msec
- •Increase of LV mass of at least 5 g/m2/year, with three measurements over a minimum of 12 months
- •Increase of left atrium (LA) size on 2D echo at least 10% above normal for age. In parasternal long axis view (PLAX) >33 mm; in four chamber view >42 mm
- •Cardiac conduction and rhythm abnormalities: atrioventricular (AV) block, short PR interval, left branch bundle block (LBBB), ventricular or atrial tachyarrhythmias, sinus bradycardia (in the absence of drugs with negative chronotropic activity)
- •Delayed posterolateral left ventricular wall late enhancement on MRI as evidence of advanced cardiac disease with fibrosis
- •Evidence of neurological involvement related to Fabry disease including 1 of the following:
- •Stroke or transient ischemic attack (TIA) prior to the age of 55 documented by a neurologist
- •Acute onset unilateral hearing loss
- •Acut monocular visual loss without other cause
- •Chronic, intractable diarrhea and/or abdominal pain/cramps, refractory to standard management for at least 6 months.
- •Chronic, intractable neuropathic pain, refractory to analgesics and standard pain management for at least 6 months.
- •Patient must have participated in Study REP001a.
排除标准
- •The patient has experienced an anaphylactic or anaphylactoid reaction or other infusion-related reaction which, in the opinion of the Investigator, precludes further treatment with agalsidase alfa or may interfere with the interpretation of the study.
- •The patient is otherwise unsuitable for the study, in the opinion of the Investigator.
- •The patient is enrolled in another clinical study, other than the Canadian Fabry Disease Initiative (CFDI).
结局指标
主要结局
Number of Participants With Infusion-Related Reactions (IRR)
时间窗: From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
An IRR (also referred to as infusion-related adverse event \[IRAE\]) was defined as an AE that began either during the infusion or within 12 hours after the start of the infusion and was judged as possibly or probably related to study drug. The IRRs were classified based on the severity as Mild=No limitation of usual activities, Moderate=Some limitation of usual activities, Severe=Inability to carry out usual activities and Life-threatening=Immediate risk of death. The number of participants with infusion-related reactions was reported.
Number of Participants Who Reported Positive to Anti-drug Antibody (ADA)
时间窗: Baseline (within 6 months prior to first dose) up to Week 285
The ADA status was measured using ELISA and electrochemiluminescent (ECL) immunoassay. Number of participants who reported positive to ADA was reported.
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
时间窗: From the start of study treatment up to 30 days after the last dose of study drug administration (up to 320 weeks)
An adverse event (AE) was any noxious, pathologic, or unintended change in anatomical, physiologic, or metabolic function as indicated by physical signs, symptoms, or laboratory changes occurring in any phase of a clinical study, whether or not considered investigational product-related.Treatment-emergent adverse events (TEAEs) were defined as those events which occurred or worsened in severity after first treatment with Replagal AF until 30 days after the last dose. A serious AE (SAE) was any AE occurred at any dose that resulted in death, life-threatening, hospitalization, prolongation of existing hospitalization, persistent or significant disability or incapacity and congenital anomaly or birth defect.
Number of Participants Who Reported Positive to Immunoglobulin A (IgA)
时间窗: Baseline (within 6 months prior to first dose) up to Week 129
The IgA status was measured using enzyme-linked immunosorbent assay (ELISA). Number of participants who reported positive to IgA was reported.
Number of Participants Who Reported Positive to Immunoglobulin E (IgE)
时间窗: Baseline (within 6 months prior to first dose) up to Week 129
The IgE status was measured using ELISA. Number of participants who reported positive to IgE was reported.
Number of Participants Who Reported Positive to Immunoglobulin M (IgM)
时间窗: Baseline (within 6 months prior to first dose) up to Week 129
The IgM status was measured using ELISA. Number of participants who reported positive to IgM was reported.
Number of Participants Who Reported Positive to Neutralizing Antibody (NAb)
时间窗: Baseline (within 6 months prior to first dose) up to Week 285
The NAb status was measured using enzyme activity inhibition assay. Number of participants who reported positive to NAb was reported.
次要结局
未报告次要终点