TY - JOUR
T1 - Phase 2 study of anti-human cytomegalovirus monoclonal antibodies for prophylaxis in hematopoietic cell transplantation
AU - Maertens, Johan
AU - Logan, Aaron C.
AU - Jang, Junho
AU - Long, Gwynn
AU - Tang, Jih Luh
AU - Hwang, William Y.K.
AU - Koh, Liang Piu
AU - Chemaly, Roy
AU - Gerbitz, Armin
AU - Winkler, Julia
AU - Yeh, Su Peng
AU - Hiemenz, John
AU - Christoph, Sandra
AU - Lee, Dong Gun
AU - Wang, Po Nan
AU - Holler, Ernst
AU - Mielke, Stephan
AU - Akard, Luke
AU - Yeo, Adeline
AU - Ramachandra, Sangana
AU - Smith, Kristin
AU - Pertel, Peter
AU - Segal, Florencia
N1 - Publisher Copyright:
Copyright © 2020 Maertens et al.
PY - 2020
Y1 - 2020
N2 - Human cytomegalovirus (HCMV) can cause significant disease in immunocompromised patients, and treatment options are limited by toxicities. CSJ148 is a combination of two anti-HCMV human monoclonal antibodies (LJP538 and LJP539) that bind to and inhibit the functions of viral HCMV glycoprotein B (gB) and the pentameric complex, consisting of glycoproteins gH, gL, UL128, UL130, and UL131. In this phase 2, randomized, placebo-controlled trial, we evaluated the safety and efficacy of CSJ148 for prophylaxis of HCMV in patients undergoing allogeneic hematopoietic stem cell transplantation. As would be expected in the study population, all the patients (100%) reported at least one treatment-emergent adverse event. There were 22 deaths during this study, and over 80% of the patients receiving placebo or CSJ148 developed at least one adverse event of grade 3 or higher severity. No subject who received antibody developed a hypersensitivity- or infusion-related reaction. CSJ148-treated patients showed trends toward decreased viral load, shorter median duration of preemptive therapy, and fewer courses of preemptive therapy. However, the estimated probability that CSJ148 decreases the need for preemptive therapy compared to placebo was 69%, with a risk ratio of 0.89 and a 90% credible interval of 0.61 to 1.31. The primary efficacy endpoint was therefore not met, indicating that CSJ148 did not prevent clinically significant HCMV reactivation in recipients of allogeneic hematopoietic cell transplants.
AB - Human cytomegalovirus (HCMV) can cause significant disease in immunocompromised patients, and treatment options are limited by toxicities. CSJ148 is a combination of two anti-HCMV human monoclonal antibodies (LJP538 and LJP539) that bind to and inhibit the functions of viral HCMV glycoprotein B (gB) and the pentameric complex, consisting of glycoproteins gH, gL, UL128, UL130, and UL131. In this phase 2, randomized, placebo-controlled trial, we evaluated the safety and efficacy of CSJ148 for prophylaxis of HCMV in patients undergoing allogeneic hematopoietic stem cell transplantation. As would be expected in the study population, all the patients (100%) reported at least one treatment-emergent adverse event. There were 22 deaths during this study, and over 80% of the patients receiving placebo or CSJ148 developed at least one adverse event of grade 3 or higher severity. No subject who received antibody developed a hypersensitivity- or infusion-related reaction. CSJ148-treated patients showed trends toward decreased viral load, shorter median duration of preemptive therapy, and fewer courses of preemptive therapy. However, the estimated probability that CSJ148 decreases the need for preemptive therapy compared to placebo was 69%, with a risk ratio of 0.89 and a 90% credible interval of 0.61 to 1.31. The primary efficacy endpoint was therefore not met, indicating that CSJ148 did not prevent clinically significant HCMV reactivation in recipients of allogeneic hematopoietic cell transplants.
KW - Hematopoietic stem cell transplantation
KW - Human cytomegalovirus
KW - Prophylaxis
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U2 - 10.1128/AAC.02467-19
DO - 10.1128/AAC.02467-19
M3 - Article
C2 - 32015031
AN - SCOPUS:85082387659
SN - 0066-4804
VL - 64
JO - Antimicrobial agents and chemotherapy
JF - Antimicrobial agents and chemotherapy
IS - 4
M1 - e02467-19
ER -