Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Mar 23:4:25.
doi: 10.3389/fped.2016.00025. eCollection 2016.

Changing the Paradigm for the Treatment and Development of New Therapies for FSGS

Cathie Spino  1 , Jordan S Jahnke  2 , David T Selewski  3 , Susan Massengill  4 , Jonathan Troost  3 , Debbie S Gipson  3
Affiliations

Changing the Paradigm for the Treatment and Development of New Therapies for FSGS

Cathie Spino et al. Front Pediatr. .

Abstract

Focal segmental glomerulosclerosis (FSGS) is a renal pathology finding that represents a constellation of rare kidney diseases, which manifest as proteinuria, edema nephrotic syndrome, hypertension, and increased risk for kidney failure. Therapeutic options for FSGS are reviewed displaying the expected efficacy from 25 to 69% depending on specific therapy, patient characteristics, cost, and common side effects. This variability in treatment response is likely caused, in part, by the heterogeneity in the etiology and active molecular mechanisms of FSGS. Clinical trials in FSGS have been scant in number and slow to recruit, which may stem, in part, from reliance on classic clinical trial design paradigms. Traditional clinical trial designs based on the "learn and confirm" paradigm may not be appropriate for rare diseases, such as FSGS. Future drug development and testing will require novel approaches to trial designs that have the capacity to enrich study populations and adapt the trial in a planned way to gain efficiencies in trial completion timelines. A clinical trial simulation is provided that compares a classical and more modern design to determine the maximum tolerated dose in FSGS.

Keywords: FSGS; adverse effects; clinical trials; nephrotic syndrome; therapy.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Models of drug development.
See this image and copyright information in PMC

References

    1. United States Renal Data System. USRDS Annual Data Report. Epidemiology of Kidney Disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; (2015).
    1. Sampson MG, Gillies CE, Robertson CC, Crawford B, Vega-Warner V, Otto EA, et al. Using population genetics to interrogate the monogenic nephrotic syndrome diagnosis in a case cohort. J Am Soc Nephrol (2015).10.1681/ASN.2015050504 - DOI - PMC - PubMed
    1. Malaga-Dieguez L, Bouhassira D, Gipson D, Trachtman H. Novel therapies for FSGS: preclinical and clinical studies. Adv Chronic Kidney Dis (2015) 22(2):e1–6.10.1053/j.ackd.2014.10.001 - DOI - PMC - PubMed
    1. Ren H, Shen P, Li X, Pan X, Zhang W, Chen N. Tacrolimus versus cyclophosphamide in steroid-dependent or steroid-resistant focal segmental glomerulosclerosis: a randomized controlled trial. Am J Nephrol (2013) 37(1):84–90.10.1159/000346256 - DOI - PubMed
    1. Fernandez-Fresnedo G, Segarra A, Gonzalez E, Alexandru S, Delgado R, Ramos N, et al. Rituximab treatment of adult patients with steroid-resistant focal segmental glomerulosclerosis. Clin J Am Soc Nephrol (2009) 4(8):1317–23.10.2215/CJN.00570109 - DOI - PMC - PubMed