Novel Therapies for Resistant FSGS (FONT II): Phase II Clinical Trial

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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