Novel Therapies for Resistant FSGS (FONTII): Phase II Clinical Trial
Condition: Focal Segmental Glomerulosclerosis
MeSH terms: Glomerulosclerosis, Focal Segmental
Intervention: Adalimumab; Lisinopril, losartan, and atorvastatin; galactose
Intervention description: Adalimumab 24 mg/m^2 (maximum dose 40 mg) sc q 14 days; Lisinopril PO 10-20 mg per day Losartan PO 25-50 mg per day Atorvastatin PO 10-20 mg per day; galactose 0.2 g/kg/dose (maximum dose 15 g)po BID
Intervention MeSH terms: Adalimumab; Losartan; Lisinopril; Atorvastatin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 1 Year
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Primary FSGS; Steroid Resistant; Rosiglitazone; Adalimumab; Resistant primary FSGS; GALACTOSE

Summary:

      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).
    

Eligibility criteria:

        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