A Randomized, Double Blind, Active Control Study of the Safety and Efficacy of PRX-102 Compared to Agalsidase Beta on Renal Function in Patients With Fabry Disease Previously Treated With Agalsidase Beta
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 78
- 试验地点
- 29
- 主要终点
- Annualized Change (Slope) in Estimated Glomerular Filtration Rate (eGFR)
研究概览
简要总结
This was a randomized, double-blind, active control study of the enzyme replacement therapy (ERT) drug PRX-102 (pegunigalsidase alfa) in Fabry disease patients with impaired renal function. Patients who had been treated for approximately 1 year with agalsidase beta and who had been on a stable dose of that product for at least 6 months were randomized in a 2:1 ratio to either switch to PRX-102 or to continue treatment with agalsidase beta. Both treatments were delivered by intravenous infusions every two weeks, at a dosage of 1 mg/kg.
详细描述
This was a randomized, double-blind, active control study examining the safety and efficacy of pegunigalsidase alfa (PRX-102) in Fabry disease patients with impaired renal function. Participants had to have been taking the licensed ERT drug agalsidase beta (Fabrazyme®) for at least 1 year prior to study entry, and to have been on a stable dose of that product for at least the last 6 months. Since the disease expresses itself differently in males and females, gender could have an impact on the therapeutic effect; thus, there was additionally a requirement that no more than 50% of the patients could be female.
Following screening, eligible patients were randomized in a 2:1 ratio to either switch to PRX-102 or continue treatment with agalsidase beta, with randomization stratified according to whether the urine protein-to-creatinine ratio (UPCR), a measure of kidney function, was above or below a specified threshold. Both products were administered as an intravenous infusion every 2 weeks, at a dosage of 1 mg/kg, for up to 24 months. Both patients and study staff were blinded as to which treatment was being given.
Patients who completed the study were invited to continue in a long-term open-label extension study, PB-102-F60, in which all participants would receive PRX-102 1 mg/kg every 2 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Symptomatic adult Fabry disease patients, age 18-60 years
- •Males: Plasma and/or leucocyte alpha galactosidase activity (by activity assay) less than 30% mean normal levels and one or more of the characteristic features of Fabry disease
- •i. neuropathic pain
- •ii. cornea verticillata
- •iii. clustered angiokeratoma
- •a. historical genetic test results consistent with Fabry pathogenic mutation and one or more of the described characteristic features of Fabry disease:
- •i. neuropathic pain
- •ii. cornea verticillata
- •iii. clustered angiokeratoma
- •b. or in the case of novel mutations a first degree male family member with Fabry disease with the same mutation, and one or more of the characteristic features of Fabry disease
- •i. neuropathic pain
- •ii. cornea verticillata
- •iii. clustered angiokeratoma
- •Screening eGFR by CKD-EPI equation 40 to 120 mL/min/1.73 m²
- •Linear negative slope of eGFR based on at least 3 serum creatinine values over approximately 1 year (range of 9 to 18 months, including the value obtained at the screening visit) of ≥ 2 mL/min/1.73 m²/year
- •Treatment with a dose of 1 mg/kg agalsidase beta per infusion every 2 weeks for at least one year and at least 80% of 13 (10.4) mg/kg total dose over the last 6 months.
- •Female patients and male patients whose co-partners are of child-bearing potential agree to use a medically accepted method of contraception, not including the rhythm method.
排除标准
- •History of anaphylaxis or Type 1 hypersensitivity reaction to agalsidase beta
- •Known non-pathogenic Fabry mutations
- •History of renal dialysis or transplantation
- •History of acute kidney injury in the 12 months prior to screening, including specific kidney diseases (e.g., acute interstitial nephritis, acute glomerular and vasculitic renal diseases); non-specific conditions (e.g, ischemia, toxic injury); as well as extrarenal pathology (e.g., prerenal azotemia, and acute postrenal obstructive nephropathy)
- •Angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy initiated or dose changed in the 4 weeks prior to screening
- •Patient with a screening eGFR value between 91-120 mL/min/1.73 m², having an historical eGFR value higher than 120 mL/min/1.73 m² (during 9 to 18 months before screening)
- •Urine protein to creatinine ratio (UPCR) > 0.5 g/g and not treated with an ACE inhibitor or ARB
- •Cardiovascular event (myocardial infarction, unstable angina) in the 6 month period before randomization
- •Congestive heart failure NYHA Class IV
- •Cerebrovascular event (stroke, transient ischemic attack) in the 6 month period before randomization
- •Known history of hypersensitivity to Gadolinium contrast agent that is not managed by the use of pre-medication
- •Female subjects who are pregnant, planning to become pregnant during the study, or are breastfeeding
- •Presence of any medical, emotional, behavioral or psychological condition that, in the judgment of the Investigator and/or Medical Director, would interfere with the patient's compliance with the requirements of the study
研究组 & 干预措施
PRX-102 (pegunigalsidase alfa)
PRX-102 infusion every 2 weeks
干预措施: PRX-102 (pegunigalsidase alfa) (Biological)
agalsidase beta
agalsidase beta infusion every 2 weeks
干预措施: agalsidase beta (Biological)
结局指标
主要结局
Annualized Change (Slope) in Estimated Glomerular Filtration Rate (eGFR)
时间窗: 24 months
The individual annualized mean change (slope) in eGFR (mL/min/1.73 m\^2/year) is an estimate of the individual patient's annualized change in eGFR, which is derived from the eGFR assessments over time, for up to 24 months. The individual annualized mean change (slope) in eGFR is estimated for each patient with at least 4 eGFR observations. For patients with fewer than 4 eGFR observations, the slope will be missing.
次要结局
- Plasma Lyso-Gb3(Baseline and Month 24)
- Estimated Glomerular Filtration Rate (eGFR)(Baseline and Month 24)
- Urine Protein/Creatinine Ratio (UPCR)(Baseline and Month 24)
- Mainz Severity Score Index (MSSI)(Baseline and Month 24)
- Left Ventricular Mass Index Without Hypertrophy at Baseline(Baseline and Month 24)
- Left Ventricular Mass Index With Hypertrophy at Baseline(Baseline and Month 24)
- Short Form Brief Pain Inventory (BPI)(Baseline and Month 24)