1. A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial of Oral Brincidofovir for Cytomegalovirus Prophylaxis in Allogeneic Hematopoietic Cell Transplantation.
- Author
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Marty, Francisco M., Winston, Drew J., Chemaly, Roy F., Mullane, Kathleen M., Shore, Tsiporah B., Papanicolaou, Genovefa A., Chittick, Greg, Brundage, Thomas M., Wilson, Chad, Morrison, Marion E., Foster, Scott A., Nichols, W. Garrett, and Boeckh, Michael J.
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CYTOMEGALOVIRUS diseases , *PREVENTIVE medicine , *CELL transplantation , *PLACEBOS , *GRAFT versus host disease - Abstract
Highlights • Prophylaxis with brincidofovir 100 mg twice weekly did not decrease clinically significant cytomegalovirus (CMV) infection (CMV disease or CMV DNAemia requiring preemptive therapy) through post-hematopoietic cell transplantation (HCT) week 24 compared with placebo. • Brincidofovir demonstrated anti-CMV activity, with decreased overall occurrence of CMV DNAemia and need for preemptive therapy through post-HCT week 24. • Brincidofovir was associated with increased gastrointestinal toxicity, which could not be differentiated from acute gastrointestinal GVHD in this blinded study with a safety management plan. ABSTRACT Cytomegalovirus (CMV) infection is a common complication of allogeneic hematopoietic cell transplantation (HCT). In this trial, we randomized adult CMV-seropositive HCT recipients without CMV viremia at screening 2:1 to receive brincidofovir or placebo until week 14 post-HCT. Randomization was stratified by center and risk of CMV infection. Patients were assessed weekly through week 15 and every third week thereafter through week 24 post-HCT. Patients who developed clinically significant CMV infection (CS-CMVi; CMV viremia requiring preemptive therapy or CMV disease) discontinued the study drug and began anti-CMV treatment. The primary endpoint was the proportion of patients with CS-CMVi through week 24 post-HCT; patients who discontinued the trial or with missing data were imputed as primary endpoint events. Between August 2013 and June 2015, 452 patients were randomized at a median of 15 days after HCT and received study drug. The proportion of patients who developed CS-CMVi or were imputed as having a primary endpoint event through week 24 was similar between brincidofovir-treated patients and placebo recipients (155 of 303 [51.2%] versus 78 of 149 [52.3%]; odds ratio,.95 [95% confidence interval,.64 to 1.41]; P =.805); fewer brincidofovir recipients developed CMV viremia through week 14 compared with placebo recipients (41.6%; P <.001). Serious adverse events were more frequent among brincidofovir recipients (57.1% versus 37.6%), driven by acute graft-versus-host disease (32.3% versus 6.0%) and diarrhea (6.9% versus 2.7%). Week 24 all-cause mortality was 15.5% among brincidofovir recipients and 10.1% among placebo recipients. Brincidofovir did not reduce CS-CMVi by week 24 post-HCT and was associated with gastrointestinal toxicity. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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