1. A randomized, placebo-controlled, dose-escalation phase I/II multicenter trial of low-dose cidofovir for BK polyomavirus nephropathy.
- Author
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Imlay H, Gnann JW Jr, Rooney J, Peddi VR, Wiseman AC, Josephson MA, Kew C, Young JH, Adey DB, Samaniego-Picota M, Whitley RJ, and Limaye AP
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Cytosine analogs & derivatives, Cytosine therapeutic use, Cytosine administration & dosage, Cytosine adverse effects, Dose-Response Relationship, Drug, Double-Blind Method, Glomerular Filtration Rate drug effects, Organophosphonates administration & dosage, Organophosphonates therapeutic use, Organophosphonates adverse effects, Treatment Outcome, Antiviral Agents administration & dosage, Antiviral Agents therapeutic use, Antiviral Agents adverse effects, BK Virus physiology, Cidofovir therapeutic use, Cidofovir administration & dosage, Kidney Diseases virology, Kidney Transplantation adverse effects, Polyomavirus Infections drug therapy, Polyomavirus Infections virology, Tumor Virus Infections drug therapy, Tumor Virus Infections virology
- Abstract
Background: BK polyomavirus-associated nephropathy (BKPyVAN) is an important cause of allograft dysfunction and failure in kidney transplant recipients (KTRs) and there are no proven effective treatments. Case reports and in vitro data support the potential activity of cidofovir against BK polyomavirus (BKPyV)., Methods: We report the results of a phase I/II, double-blind, placebo-controlled randomized dose-escalation trial of cidofovir in KTRs with biopsy-confirmed BKPyVAN and estimated glomerular filtration rate ≥30 mL/min. Intravenous cidofovir (0.25 mg/kg/dose or 0.5 mg/kg/dose) or placebo was administered on days 0, 7, 21, and 35, with final follow-up through day 49., Results: The trial was prematurely discontinued due to slow accrual after 22 KTRs had completed the study. Cidofovir was safe and tolerated at the doses and duration studied. The proportion of subjects with any adverse event (AE) was similar between groups (9/14 [64%] in the combined cidofovir dose groups and 6/8 [75%] in the placebo group); 84% of AEs were mild. BKPyV DNAemia reduction by day 49 was similar between groups (>1 log
10 reduction in (2/9 [22.2%] of 0.25 mg/kg group, 1/5 [20%] of 0.5 mg/kg group, and 2/8 [25%] of placebo group)., Conclusions: These preliminary results indicate that low-dose cidofovir was safe and tolerated but had no significant BKPyV-specific antiviral effect in KTRs with BKPyVAN., (© 2024 The Author(s). Transplant Infectious Disease published by Wiley Periodicals LLC.)- Published
- 2024
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