A Phase 2, Double-Blind, Placebo-Controlled, Randomized Study of Fresolimumab in Patients With Steroid-Resistant Primary Focal Segmental Glomerulosclerosis
| Autor: | Sara Engstrand, James A. Tumlin, Kirk N. Campbell, Fernando C. Fervenza, Manuel Praga, John F. Neylan, Loreto Gesualdo, Steven R. Ledbetter, Montserrat Díaz, Beverly Accomando, Julie Lin, Jai Radhakrishnan, Flavio Vincenti, Denyse Thornley-Brown, Ajay K. Singh, Francisco Veríssimo Veronese, Peter T. Nelson, Lorenz Sellin |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Urology Renal function lcsh:RC870-923 Placebo urologic and male genital diseases law.invention 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Focal segmental glomerulosclerosis Randomized controlled trial Clinical Research law Medicine 030212 general & internal medicine Creatinine Proteinuria Primary Focal Segmental Glomerulosclerosis business.industry urogenital system Fresolimumab food and beverages steroid-resistant primary focal segmental glomerulosclerosis lcsh:Diseases of the genitourinary system. Urology medicine.disease fresolimumab female genital diseases and pregnancy complications Surgery 030104 developmental biology chemistry Nephrology monoclonal antibody medicine.symptom proteinuria business |
| Zdroj: | Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid Consejería de Sanidad de la Comunidad de Madrid Kidney International Reports Kidney International Reports, Vol 2, Iss 5, Pp 800-810 (2017) |
| ISSN: | 0166-5391 |
| Popis: | Introduction Steroid-resistant focal segmental glomerulosclerosis (SR-FSGS) is a common glomerulopathy associated with nephrotic range proteinuria. Treatment goals are reduction in proteinuria, which can delay end-stage renal disease. Methods Patients with SR-FSGS were enrolled in a randomized, double-blind placebo-controlled trial of fresolimumab, a monoclonal anti−transforming growth factor−β antibody, at 1 mg/kg or 4 mg/kg for 112 days, followed double-blind for 252 days (NCT01665391). The primary efficacy endpoint was the percentage of patients achieving partial (50% reduction) or complete (< 300 mg/g Cr) remission of proteinuria. Results Of 36 enrolled patients, 10, 14, and 12 patients received placebo, fresolimumab 1 mg/kg, and fresolimumab 4 mg/kg, respectively. The baseline estimated glomerular filtration rate (eGFR) and urinary protein/creatinine ratio were 63 ml/min/1.73 m2 and 6190 mg/g, respectively. The study was closed before reaching its target of 88 randomized patients. None of the prespecified efficacy endpoints for proteinuria reduction were achieved; however, at day 112, the mean percent change in urinary protein/creatinine ratio (a secondary efficacy endpoint) was –18.5% (P = 0.008), +10.5% (P = 0.52), and +9.0% (P = 0.91) in patients treated with fresolimumab 1 mg/kg, fresolimumab 4 mg/kg, and placebo, respectively. There was a nonsignificant trend toward greater estimated glomerular filtration rate decline in the placebo group compared to either of the fresolimumab-treated arms up to day 252. Discussion The study was underpowered and did not meet the primary or secondary endpoints. However, fresolimumab was well tolerated and is appropriate for continued evaluation in larger studies with adequate power. |
| Databáze: | OpenAIRE |
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