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

Hannah Imlay; John W Gnann Jr; James Rooney; V Ram Peddi; Alexander C Wiseman; Michelle A Josephson; Clifton Kew; Jo-Anne H Young; Deborah B Adey; Milagros Samaniego-Picota; Richard J Whitley; Ajit P Limaye

doi:10.1111/tid.14367

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

Transpl Infect Dis. 2024 Sep 3:e14367. doi: 10.1111/tid.14367. Online ahead of print.

Authors

Affiliations

¹ Department of Internal Medicine, University of Utah, Salt Lake City, Utah, USA.
² Department of Medicine, Medical University of South Carolina University Medical Center, Charleston, South Carolina, USA.
³ Gilead Sciences, Foster City, California, USA.
⁴ Department of Transplantation, California Pacific Medical Center, San Francisco, California, USA.
⁵ Department of Medicine, University of Colorado at Denver Health Sciences Center, Denver, Colorado, USA.
⁶ Department of Medicine, University of Chicago, Chicago, Illinois, USA.
⁷ Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
⁸ Department of Medicine, University of Minnesota, Minneapolis, Minnesota, USA.
⁹ Department of Medicine, University of California at San Francisco, San Francisco, California, USA.
¹⁰ Department of Medicine, University of Wisconsin Medical School, Madison, Wisconsin, USA.
¹¹ Department of Pediatrics, University of Alabama, Birmingham, Alabama, USA.
¹² Department of Internal Medicine, University of Washington, Seattle, Washington, USA.

PMID: 39226143
DOI: 10.1111/tid.14367

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 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.

Keywords: BK virus; cidofovir; kidney transplant; randomized controlled trial.

Grants and funding

AI-30025/National Institute of Allergy and Infectious Diseases