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

• Status: Completed
• Trial end date: 2014-02-01
• Target enrollment: 0
• Participant gender: All

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).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: New York University School of Medicine; NYU Langone Health
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); The Cleveland Clinic; University of Michigan
• Treatments: Adalimumab; Atorvastatin; Atorvastatin Calcium; Lisinopril; Losartan

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