Phase 1 Study of Anti-CTGF Monoclonal Antibody in Patients with Diabetes and Microalbuminuria
| Autor: | Sherwyn Schwartz, Mark E. Williams, Carlos J. Arauz-Pacheco, Thomas B. Neff, Warren K. Bolton, Dongxia Li, Pedro R. Urquilla, Tyson Lee, K. Lea Sewell, Sharon G. Adler |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Adult
Male medicine.medical_specialty Epidemiology Urology Renal function Antibodies Monoclonal Humanized Critical Care and Intensive Care Medicine Drug Administration Schedule chemistry.chemical_compound Fibrosis Diabetes mellitus Internal medicine medicine Albuminuria Humans Hypoglycemic Agents Diabetic Nephropathies Infusions Intravenous Adverse effect Aged Transplantation Creatinine Proteinuria business.industry Connective Tissue Growth Factor Antibodies Monoclonal Original Articles Middle Aged medicine.disease Diabetes Mellitus Type 1 Kidney Tubules Treatment Outcome Endocrinology Diabetes Mellitus Type 2 chemistry Nephrology Female Microalbuminuria medicine.symptom business Glomerular Filtration Rate |
| Zdroj: | Clinical Journal of the American Society of Nephrology. 5:1420-1428 |
| ISSN: | 1555-9041 |
| DOI: | 10.2215/cjn.09321209 |
| Popis: | Background and objectives: This report summarizes the first phase 1 trial treating patients with microalbuminuric diabetic kidney disease (DKD) using FG-3019, a human monoclonal antibody to connective tissue growth factor (CTGF). CTGF is critically involved in processes of progressive fibrosis, including DKD. This phase 1, open-label, dose-escalation trial evaluated safety, pharmacokinetics, and possible therapeutic effects of FG-3019 on albuminuria, proteinuria, and tubular proteins. Design, setting, participants, and measurements: Microalbuminuric subjects (n = 24) with type 2 (79%) or type 1 (21%) diabetes received 3 or 10 mg/kg FG-3019 dosed intravenously every 14 days for four doses. Albuminuria and safety follow-up were to days 62 and 365, respectively. Results: No infusion was interrupted for symptoms, although 5 of 24 subjects had mild infusion-day adverse events thought to be possibly drug-related. No subject developed anti-FG-3019 antibodies. FG-3019 clearance was lower at 10 mg/kg than at 3 mg/kg, suggesting a saturable elimination pathway. Although this study was not designed for efficacy testing, it was notable that urinary albumin/creatinine ratio (ACR) decreased significantly from mean pretreatment ACR of 48 mg/g to mean post-treatment (day 56) ACR of 20 mg/g (P = 0.027) without evidence for a dose-response relationship. Conclusions: Treatment of microalbuminuric DKD subjects using FG-3019 was well tolerated and associated with a decrease in albuminuria. The data demonstrate a saturable pathway for drug elimination, minimal infusion adverse events, and no significant drug-attributable adverse effects over the year of follow-up. Changes in albuminuria were promising but require validation in a prospective, randomized, blinded study. |
| Databáze: | OpenAIRE |
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