A randomized, double-blind, placebo-controlled phase 3 trial of oral brincidofovir for cytomegalovirus prophylaxis in allogeneic hematopoietic cell transplantation Journal Article
| Authors: | Marty, F. M.; Winston, D. J.; Chemaly, R. F.; Mullane, K. M.; Shore, T. B.; Papanicolaou, G. A.; Chittick, G.; Brundage, T. M.; Wilson, C.; Morrison, M. E.; Foster, S. A.; Nichols, W. G.; Boeckh, M. J.; on behalf of the SUPPRESS Trial Clinical Study Group |
| Article Title: | A randomized, double-blind, placebo-controlled phase 3 trial of oral brincidofovir for cytomegalovirus prophylaxis in allogeneic hematopoietic cell transplantation |
| 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. © 2018 |
| Keywords: | adult; controlled study; aged; major clinical study; fatigue; placebo; diarrhea; hypertension; side effect; mucosa inflammation; nausea; randomized controlled trial; vomiting; aciclovir; sex ratio; abdominal pain; coughing; fever; hyperglycemia; hypomagnesemia; rash; alanine aminotransferase; hypokalemia; insomnia; acute graft versus host disease; prophylaxis; hematopoietic cell; peripheral edema; allogeneic hematopoietic stem cell transplantation; hyperbilirubinemia; headache; maximum plasma concentration; phase 3 clinical trial; infection prevention; tacrolimus; double blind procedure; rapamycin; cytomegalovirus infection; cyclosporine; cytomegalovirus; infection risk; graft recipient; alemtuzumab; plasma concentration-time curve; thymocyte antibody; allogeneic hematopoietic cell transplantation; adverse event; decreased appetite; valaciclovir; mycophenolic acid; antiviral; human; male; female; article; brincidofovir; cmx001; all cause mortality |
| Journal Title: | Biology of Blood and Marrow Transplantation |
| Volume: | 25 |
| Issue: | 2 |
| ISSN: | 1083-8791 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2019-02-01 |
| Start Page: | 369 |
| End Page: | 381 |
| Language: | English |
| DOI: | 10.1016/j.bbmt.2018.09.038 |
| PUBMED: | 30292744 |
| PROVIDER: | scopus |
| PMCID: | PMC8196624 |
| DOI/URL: | |
| Notes: | Export Date: 1 February 2019 -- Source: Scopus |
