A randomized, placebo‐controlled, dose‐escalation phase I/II multicenter trial of low‐dose cidofovir for BK polyomavirus nephropathy

• Published in: Transplant infectious disease Vol. 26; no. 6; pp. e14367 - n/a
• Main Authors: Imlay, Hannah, Gnann, John W., Rooney, James, Peddi, V. Ram, Wiseman, Alexander C., Josephson, Michelle A., Kew, Clifton, Young, Jo‐Anne H., Adey, Deborah B., Samaniego‐Picota, Milagros, Whitley, Richard J., Limaye, Ajit P.
• Format: Journal Article
• Language: English
• Published: Denmark Wiley Subscription Services, Inc 01.12.2024; John Wiley and Sons Inc
• Subjects: Adult; Aged; Allografts; Antiviral Agents - administration & dosage; Antiviral Agents - adverse effects; Antiviral Agents - therapeutic use; Antiviral drugs; Biopsy; BK virus; BK Virus - physiology; Case reports; Cidofovir; Cidofovir - administration & dosage; Cidofovir - therapeutic use; Cytosine - administration & dosage; Cytosine - adverse effects; Cytosine - analogs & derivatives; Cytosine - therapeutic use; Dose-Response Relationship, Drug; Double-Blind Method; Female; Glomerular filtration rate; Glomerular Filtration Rate - drug effects; Humans; In vitro methods and tests; Kidney Diseases - virology; kidney transplant; Kidney transplantation; Kidney Transplantation - adverse effects; Male; Middle Aged; Nephropathy; Organophosphonates - administration & dosage; Organophosphonates - adverse effects; Organophosphonates - therapeutic use; Original; Placebos; Polyomavirus Infections - drug therapy; Polyomavirus Infections - virology; randomized controlled trial; Renal failure; Treatment Outcome; Tumor Virus Infections - drug therapy; Tumor Virus Infections - virology; cidofovir; kidney transplant; BK virus; randomized controlled trial
• ISSN: 1398-2273; 1399-3062; 1399-3062
• DOI: 10.1111/tid.14367

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 log10 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. In a randomized, placebo‐controlled, dose‐escalation phase I/II multicenter trial of low‐dose cidofovir for BK polyomavirus nephropathy, cidofovir was found to be safe and tolerated but demonstrated no significant BK polyomavirus‐specific antiviral effect.