Format

Send to

Choose Destination
Biol Blood Marrow Transplant. 2019 Feb;25(2):369-381. doi: 10.1016/j.bbmt.2018.09.038. Epub 2018 Oct 4.

A Randomized, Double-Blind, Placebo-Controlled Phase 3 Trial of Oral Brincidofovir for Cytomegalovirus Prophylaxis in Allogeneic Hematopoietic Cell Transplantation.

Author information

1
Dana-Farber Cancer Institute, Boston, Massachusetts; Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: fmarty@bwh.harvard.edu.
2
Department of Medicine, Ronald Reagan UCLA Medical Center, Los Angeles, California.
3
Department of Infectious Diseases, Infection Control, and Employee Health, University of Texas M.D. Anderson Cancer Center, Houston, Texas.
4
Department of Medicine, University of Chicago, Chicago, Illinois.
5
Department of Medicine, Weill Cornell Medical College/New York Presbyterian Hospital, New York, New York.
6
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York.
7
Chimerix, Inc, Durham, North Carolina.
8
Department of Medicine, University of Washington, Seattle, Washington; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.

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.

KEYWORDS:

Allogeneic hematopoietic cell transplantation; Antiviral; Brincidofovir; CMX001; Cytomegalovirus; Prophylaxis

PMID:
30292744
DOI:
10.1016/j.bbmt.2018.09.038
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center