Novel Therapies for Resistant Focal Segmental Glomerulosclerosis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 18
- 主要终点
- Number of Participants With a Reduction in Proteinuria at 6 Months by > 50% of the Value at Screening AND Stable GFR Defined as Greater Than 75 ml/Min/1.73m2 in Those With an Initial Value Above 90 OR Within 25% of Baseline for Remaining Patients
研究概览
简要总结
This project will test whether adalimumab,and/or galactose can safely reduce proteinuria (abnormal amounts of protein in the urine) and protect kidney function better than standard treatment for patients with focal segmental glomerulosclerosis (FSGS).
详细描述
SPECIFIC AIMS A significant percentage of patients with primary FSGS are resistant to corticosteroids and other immunosuppressive medications. In view of the rising incidence of this disease and the grim prognosis for patients with resistant disease, it is imperative that new therapeutic approaches be evaluated in an efficient and systematic manner. This will enable accurate assessment of the risk-benefit ratio of novel therapies and guide the design of future Phase III randomized clinical trials.
Specific Aim #1: To evaluate two novel therapies for resistant FSGS -- anti-TNF-α antibody and galactose -- against standard therapy
Specific Aim #2: To identify one or more novel agents as candidates for future study in a Phase III randomized clinical trial
OVERALL STUDY DESIGN Screening/Run-In: There is no formal run-in period in the phase II trial because patients with resistant FSGS who will be eligible for this study often have unstable kidney function and are prone to sudden decline in glomerular filtration rate (GFR). An effort will be made to achieve randomization within 2 weeks of the screening visit.
In order to achieve a comparable baseline assessment prior to initiation of one of the novel therapies, the patients must be off all immunosuppressive medications for 30 days. In addition, patients will be placed on the maximal tolerated doses of an angiotensin-converting enzyme inhibitor (ACEI), an angiotensin receptor blocker (ARB), and a lipid-lowering drug defined above based upon measurements of blood pressure, serum K+, creatinine, and cholesterol concentrations. Patients will have to be on stable doses of the ACEI/ARB treatment for a minimum of 2 weeks prior to randomization into the FONT Phase II study to insure that the initiation of novel therapy does not coincide with a hemodynamically induced change in proteinuria. In order to implement this part of conservative medical therapy, a 2-12 week Screening/Run-In period will precede randomization. Rescreening will be necessary if patients are not randomized to one of the three treatment arms within 12 weeks of the initial screening assessment.
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
- None
入排标准
- 年龄范围
- 1 Year 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Primary FSGS confirmed by renal biopsy OR documentation of a genetic mutation in a podocyte protein associated with the disease
- •Failure to respond to prior therapy at least one of the following immunosuppressive medications -- cyclosporine, tacrolimus, mycophenolate mofetil, sirolimus - or other agents prescribed to lower proteinuria
- •Age 1-65 years at onset of proteinuria
- •Age 1-65 years at time of randomization
- •Estimated GFR ≥40 mL/min/1.73 m2 using Schwartz (age <18 yr) or Cockroft-Gault (age <18 yr) formula at screening and ≥30 mL/min/1.73 m2 at the end of the Run-In Period and at the time of randomization
- •Up/c > 1.0 g/g creatinine on first morning void
- •Steroid resistance defined as failure to achieve sustained Up/c < 1.0 following a standard course of prednisone/prednisolone/methylprednisolone prescribed for FSGS therapy, OR contraindication/anticipated intolerance to steroid therapy defined as severe obesity, documented decreased bone density, family history of diabetes, or a psychiatric disorder.
- •Willingness to follow the protocol, including medications, baseline and follow-up visits, and procedures.
排除标准
- •Lactation, pregnancy, or refusal of birth control in women of child bearing potential
- •Participation in another therapeutic trial involving protocol mandated administration of a immunosuppressive medication concurrently or 30 days prior to randomization
- •Active/serious infection (including, but not limited to Hepatitis B or C, HIV)
- •History of malignancy
- •Abnormality in age appropriate cancer screening in accord with ACS 2003 guidelines (appendix 17.6)
- •Patients with uncontrolled blood pressure > 140/90 or > 95th percentile for age/height at the end of the run in period
- •Diabetes mellitus Type I or II
- •Organ transplantation
- •Congestive heart failure
- •History of prior myocardial infarction
- •SLE or multiple sclerosis
- •Hepatic disease, defined as serum ALT/AST levels more than 2.5x the upper limit of normal
- •Hematocrit <27%
- •Immunosuppressive therapy with cyclosporine, tacrolimus, mycophenolate mofetil, azathioprine, or rapamycin in the 30 days prior or Rituximab in the 90 days prior to randomization
- •Prior treatment with the study medications, rosiglitazone or adalimumab
- •Allergy to one of the study medications, i.e., rosiglitazone, adalimumab, lisinopril, losartan or atorvastatin
研究组 & 干预措施
2
Conservative medical therapy plus adalimumab
干预措施: Adalimumab (Drug)
1
Conservative medical therapy (lisinopril, losartan, atorvastatin)
干预措施: Lisinopril, losartan, and atorvastatin (Drug)
conservative medical therapy plus galactose
drug: galactose 0.2 g /kg/dose (maximum dose 15g) po BID
干预措施: galactose (Drug)
结局指标
主要结局
Number of Participants With a Reduction in Proteinuria at 6 Months by > 50% of the Value at Screening AND Stable GFR Defined as Greater Than 75 ml/Min/1.73m2 in Those With an Initial Value Above 90 OR Within 25% of Baseline for Remaining Patients
时间窗: baseline and 6 months
Number of participants with a reduction in proteinuria at 6 months by \> 50% of the value at screening AND stable GFR defined as greater than 75 ml/min/1.73m2 in those with an initial value above 90 OR within 25% of baseline for remaining patients.
次要结局
- Number of Participants With Adverse Events(Up to 7 months)
- Percent Change in Proteinuria(Baseline and 6 months)
- Percent Change in or Time to Doubling of Serum Creatinine(Baseline and 6 months)
- Patient Satisfaction Score Using the Treatment Satisfaction Questionnaire for Medication (TSQM Questionnaire)(Baseline and 6 months)