• Male and Female FSGS Patients between 18-70 years old.
•  GFR≥30ml/min/1.73m2 calculated by the MDRD equation;
• Urinary total protein: creatinine ratios >300mg/mmol derived from the average of 2 first morning voids taken during screening period;
• Biopsy confirmed as idiopathic FSGS by a central reviewer;
• Patients who have received minimum 6 week course of steroids or immunosuppressant.
• If receiving treatment with an ACEi and/or ARB dose to be stable for a minimum of 4 weeks prior to randomization;
• Influenza vaccine (according to season);
• Negative screening per American Cancer Society (ACS) 2003 guidelines, as appropriate to patient demographics and clinical status. 

• Estimated GFR ≥ 40 ml/min/1.73 m2 at most recent measure prior to randomization- For participants < age 18 years: Schwartz formula For participants ≥ age 18 years: Cockroft-Gault formula; Up/c > 1.0 g protein/g creatinine on first am void at time of randomization
• Biopsy confirmed as primary FSGS (including all subtypes) by study pathologist, a minimum of 1 glomerulus demonstrating segmental sclerosis on light microscopy will be required to confirm the diagnosis. 
• Participants must also be steroid resistant: The participant must have demonstrated steroid resistance (defined as a failure to achieve a sustained Up/c ≤ 1.0) based on at least one treatment course with high dose steroids prior to randomization which satisfies both of the following conditions: minimal treatment duration of 4 weeks, minimum cumulative dose of 56 mg/kg or 1680 mg of prednisone or its equivalent.
• The participant must not have had a complete remission of proteinuria (Up/c < 0.2 or dipstick urine protein 0/trace) subsequent to the latest qualifying 4-week course demonstrating steroid resistance.
• Participants must demonstrate a willingness to follow the clinical trial protocol, including medications, and baseline and follow-up visits and procedures.
• Participants may be taking ACEI, ARB, Vitamin E, or lipid lowering therapy.

• An adequate renal biopsy, defined as having a minimum of 10 glomeruli for light microscopy and a minimun of 3 glomeruli for electron microscopy. Patients who have biopsies that contain fewer glomeruli will be offered the opportunity to undergo a research biopsy to determine eligibility.
• Adults greater than 18 years of age.
• Prior treatment with at least two immunosppressive agents that have been shown to induce remission in MCD and FSGS: glucocorticoids, cyclosporine, tacrolimus, cyclophosphamide, chlorambucil, and mycophenolate mofetil. Therapy with each agent must last at least 8 weeks. Exemptions will be made for those with contraindications to these medications or those who cannot tolerate these medications. The rationale is to recruit patients who have failed conventional therapy.
• All patients will be off immunosuppression for at least 4 weeks before starting retiniods in order to avoid a confounding effect. Three 24h urine collections with mean protein excretion greater than or equal to 3.5 g/d obtained within one month prior to enrolling in the study. These 24hr urine collections will be collected after the patient has been on a stable dose of ACE inhibitor or ARB for at least 4 weeks (the maximal antiproteinuric effect of these medications occurs after 4 weeks). The rationale is that patients with nephrotic-range proteinuria are at high risk for progressive renal disease, justifying participation in a clinical trial with novel agents.
• Blood pressure of less than or equal to 130/80 on a stable dose of ACE inhibitor or ARB for at least 1 month or greater than or equal to 75 percent of measurements before the entry of the study. The rationale is that uncontrolled hypertension can exacerbate proteinuria.

• Biopsy-proven MCD and its variants, including IgM nephropathy and MCD with mesangial hypertrophy. Biopsy-proven FSGS, including idiopathic FSGS and collapsing FSGS.
• Proteinuria: patients must have nephrotic range proteinuria. Baseline tests will be obtained when patients have been off all immunosuppressive therapy for greater than or equal to 1 month. Renal function: estimated GFR must be greater than or equal to 40 ml/min/1.73m(2) at the time of study entry; In children weighing less than 40kg, GFR will be estimated by the Schwartz formula and expressed as GFR/1.73m(2): GFR equal to [0.7 (males) or 0.57 (females) X height (cm)]/ serum creatinine.
• Angiotensin antagonists: Patients must be receiving angiotensin antagonist therapy, at any dose approved by the FDA. Nephrotic range proteinuria will be defined as urine protein greater than or equal to 3.5 g/1.73m(2)/d (adults) and greater than 50 mg/kg (children less than 40 kg) while receiving maximally tolerated dose of angiotensin antagonist therapy for at least 4 weeks prior to study entry.
• Must also have prior immunosuppressive therapy: For children with MCD, we require a minimum of 4 weeks and a maximum of 10 weeks of daily steroid therapy at a dose of greater than or equal to 60 mg/m(2) with proteinuria persisting in the nephrotic range (excluding steroid-sensitive, steroid-dependent and frequently relapsing MDC). For children with FSGS and adults with MCD and FSGS, we require no minimum and a maximum of 8 weeks of daily or alternate day steroids at a dose of greater than 0.5 mg/kg with proteinuria persisting in the nephrotic range.
• Patients with prior immunosuppressive therapy other than steroids are eligible. Patients must either have a negative PPD test within 3 months of study entry while off immunosuppressive therapy or, if they have a history of positive PPD, they must have appropriate evaluation to exclude untreated tuberculosis (with the advice of an Infectious Disease consultant).

To find additional information on any of these studies please visit: http://clinicaltrials.gov/ct2/results?term=focal+segmental+Glomerulosclerosis

---

To read more, visit the NephCure Archive of FSGS Trials and Workshop.