Multi-center, Open-label Study of the Safety and Efficacy of Control of Proteinuria With ACE Inhibitors and ARBS in Patients With Fabry Disease Who Are Receiving Fabrazyme®: The FAACET Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 36
- 试验地点
- 6
- 主要终点
- Determine the relationship of GFR to titrating ACEI/ARB therapy to targeted uring protein ration
研究概览
简要总结
The primary hypothesis is that titration of ACE inhibitor and Angiotensin Receptor Blockers (ARBs)to reduce urine protein excretion to < 500 mg per day in Fabry Patients receiving agalsidase beta therapy at 1 mg/kg every two weeks will slow the progression rate of decline of glomerular filtration rate (GFR) compared to case controls drawn from the Genzyme-sponsored Phase III extension study (GFR 60 to 125 ml/min/1.73 m², urine protein > 1 gram/day) or the Phase IV study (GFR 20 to 60 ml/min/1.73 m², urine protein > 0.5 gram/day). After a 3 month initial Evaluation Phase, the patients will be followed during a 24 month Observation Phase. FAACET is an open label, prospective observational study. The primary objective is reduction of first morning urine protein/creatinine ratio to < 0.5 gram/gram. The primary outcome measure is the regression slope of MDRD GFR with time in years
详细描述
TITLE: FABRAZYME® + ARBS + ACE INHIBITOR TREATMENT (FAACET) STUDY Multi-center, Open-label Study of the Safety and Efficacy of Control of Proteinuria with Angiotensin Receptors Blockers (ARBs) and Angiotensin Converting Enzyme Inhibitors (ACEIs) in Patients with Fabry Disease Who Are Receiving Fabrazyme®.
PROTOCOL NO. UAB NEPHROLOGY 001-2006 SPONSOR: University of Alabama at Birmingham, Birmingham, AL 35294 NAME OF FINISHED PRODUCTS: Angiotensin Converting Enzyme Inhibitors, Angiotensin Receptor Blockers, Fabrazyme® INVESTIGATOR/STUDY CENTERS: Fourteen (14) study sites worldwide PRIMARY OBJECTIVE To determine whether decline of GFR can be slowed by titrating ACEI/ARB anti-proteinuric therapy to target urine protein/creatinine ratio of ≤ 0.5, or 50% reduction from baseline, in Fabry patients with significant kidney involvement (20 ≤ eGFRMDRD ≤ 60 ml/min/1.73 m²), and baseline urine protein/creatinine ratio > 0.5 (based on the last value obtained before initiating ACEI/ARB therapy or obtained at screening before the first Evaluation Visit of the FAACET Study), who are receiving standard of care treatment for Chronic Kidney Disease (CKD), and Fabry disease.
SECONDARY OBJECTIVES
- To determine whether urine protein/creatinine ratio ≤ 0.5, or ≥ 50% reduction from baseline, can safely be achieved in Fabry patients with ACEI/ARB therapy.
- To determine whether urine protein/creatinine ratio ≤ 0. 5, or ≥ 50% reduction from baseline, result in a slower rate of GFR decline compared to patients who cannot achieve this target.
- To determine if GFR decline can be slowed by titrating ACEI/ARB therapy to target urine protein/creatinine ratio ≤ 0.5, or 50% reduction from baseline, in Fabry patients with definite kidney involvement (125 ≥ eGFRMDRD ≥ 60 ml/min/1.73 m²), and baseline urine protein/creatinine ratio > 1.0 (based on the last value obtained before initiating ACEI/ARB therapy or obtained at screening before the first Evaluation Visit of the FAACET Study) who are receiving standard of care treatment for Chronic Kidney Disease (CKD), and Fabry disease.
METHODOLOGY This will be a multi-center, multinational, open-label study to confirm the safety and the effectiveness of ACE inhibitors and ARBs against proteinuria in patients with advanced Fabry disease who are receiving Fabrazyme® at 1 mg/kg every other week. Following an initial 3-month Evaluation Period, during which ACEI/ARB therapy will be titrated to reduce urinary protein/creatinine ratio to a target of 0.5, or 50% of baseline level, the patients will be followed for 24 months in an Observation Period with continued monitoring of their eGFRMDRD and protein excretion every 3 monthly for 24 months. ACEI/ARB therapy will continue to be titrated to maintain the proteinuria target in the Observation Period. The baseline urine protein/creatinine ratio is defined as the last value obtained in the individual patient before they began any ACEI/ARB therapy.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 19 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient must provide written, informed consent, and be ≥ 19 yrs of age.
- •The patient is already receiving Fabrazyme® at 1 mg/kg every two weeks at the time of enrollment.
- •Patient has confirmed Fabry disease (plasma αGAL activity of < 1.5 nmol/hr/mL, or leukocyte αGAL activity of < 4 nmol/hr/mg), or a known mutation compatible with Fabry disease.
- •Patients with either:
- •eGFRMDRD ≥ 20 and ≤ 60 ml/min/1.73 m2, and documented baseline urine protein/creatinine ratio > 0.5, based on the last value obtained before initiating ACEI/ARB therapy or obtained at screening before the first Evaluation Visit of the FAACET Study; or
- •eGFRMDRD ≤ 125 ml/min/1.73 m2 and > 60 ml/min/1.73 m2 with documented baseline urine protein/creatinine ratio > 1, based on the last value obtained before initiating ACEI/ARB therapy or obtained at screening before the first Evaluation Visit of the FAACET Study.
排除标准
- •The patient has undergone kidney transplantation or is currently on dialysis, or is planning on receiving a kidney transplant during the first year of the study.
- •The patient has diabetic nephropathy or the presence of another, confounding kidney disease unless there is kidney biopsy confirmation that the patient does not have diabetic nephropathy or another, confounding kidney disease.
- •The patient has a clinically significant organic disease, or other condition that in the opinion of the investigator would preclude participation in the full extent of the trial.
- •The patient is unwilling to comply with the requirements of the protocol, including continuing on Fabrazyme® at 1 mg/kg body weight every two weeks.
- •Patients who have documented allergies to ACE inhibitors and to ARBs are not eligible to participate in the FAACET Study.
- •The patient is pregnant or intends to become pregnant during the course of the study.
结局指标
主要结局
Determine the relationship of GFR to titrating ACEI/ARB therapy to targeted uring protein ration
时间窗: from baseline
To determine whether decline of GFR can be slowed by titrating ACEI/ARB anti-proteinuric therapy to target urine protein/creatinine ratio of ≤ 0.5, or 50% reduction from baseline, in Fabry patients with significant kidney involvement (20 ≤ eGFRMDRD ≤ 60 ml/min/1.73 m²), and baseline urine protein/creatinine ratio \> 0.5 (based on the last value obtained before initiating ACEI/ARB therapy or obtained at screening before the first Evaluation Visit of the FAACET Study), who are receiving standard of care treatment for Chronic Kidney Disease (CKD), and Fabry disease.
次要结局
- Determine if GFR decline can be slowed by titrating ACEI/ARB therapy to target urine protein/creatinine ratio ≤ 0.5, or 50% reduction(baseline to first visit)
- Decrease in protein/creatinine ratio after administration of AECI/ARB therapy(from baseline)
- Determine if urine protein/creaine reduction results in slower GFR decline(from baseline)