MULTICENTER RANDOMIZED CLINICAL TRIAL OF FSGS IN CHILDREN AND YOUNG ADULTS J Gassman, R Fine, A Friedman, D Gipson, T Greene, R Hogg, F Kaskel, M Moxey-Mims, M Radeva, N Siegel*, H Trachtman, S Watkins NIH NIDDK, Bethesda MD *deceased

Objectives Randomized trial to compare 2 therapeutic interventions for patients 2 – 40 yrs of age with steroid resistant FSGS Facilitate the investigation of complex pathobiology of FSGS Target sample size is 207 randomized patients to achieve 80% power to detect 17.9% absolute difference in remission rate

Outcomes Primary Outcome Attainment of partial or complete remission (6-level ordinal scale) Main Secondary Outcome No relapse after withdrawal of immunosuppressive agents Secondary Outcomes Treatment failures Change in eGFR Side effects Quality of life Biological materials

The primary outcome is defined as achievement of remission from proteinuria during the first 52 weeks after randomization *Complete remission: Decline in UP/C to no > than 0.2 *Partial remission: 50% or > decline to a level between 0.2 and 2.0 * Mean of 2 baseline measurements of first morning urine Primary Outcome Measures

Definition of Primary Outcome at 52 Weeks for Participants Achieving a Partial or Complete Remission at 26 Weeks Remission Category Sustained complete remission Limited complete remission Partial remission No remission Level1234 Definition Complete remission throughout weeks Complete remission at W52 but Up/c > 0.2 between weeks 26 and 52 Partial remission at W52 No remission at W52

Main Secondary Outcome Measures 5-level ordinal categorical outcome based on the participant’s level of proteinuria during the period from W52 through W78 following withdrawal of CSA or MMF/Pulse steroids Participants remain on ACEi / ARB

Definition of Main Secondary Outcome at Week 78 for Participants with a Primary Outcome Level of at least 3 Remission Category Full persistence of complete remission Limited persistence of complete remission Partial remissionNo remission LevelABCD Definition Complete remission throughout weeks Complete remission at week 78, but Up/c between 0.2 and 2.0 between weeks 52 and 78 Partial remission at week 78, and partial or complete remission between weeks 52 and 78 Failure to maintain at least a partial remission after week 52 Note: Participants who were assigned to levels 4, 5, or 6 for the primary outcome at the 26 and/or 52 week assessment will be assigned to level E for the main secondary outcome.