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Antimicrob Agents Chemother. 2020 Feb 3. pii: AAC.02467-19. doi: 10.1128/AAC.02467-19. [Epub ahead of print]

Anti-human cytomegalovirus monoclonal antibodies for prophylaxis in hematopoietic cell transplantation: a phase 2 study.

Author information

1
Universitaire Ziekenhuizen Leuven, Leuven, Belgium.
2
University of California, San Francisco Medical Center, California, USA.
3
Samsung Medical Center, Seoul, South Korea.
4
Duke University Medical Center, North Carolina, USA.
5
National Taiwan University, Taipei, Taiwan.
6
Singapore General Hospital, Singapore.
7
National University cancer Institute Singapore, Singapore.
8
University of Texas Anderson Cancer Center, Texas, USA.
9
Universitatsklinikum Erlangen, Erlangen, Germany.
10
China Medical University Hospital, Taichung, Taiwan.
11
University of Florida Health Shands Cancer Hospital, Florida, USA.
12
Universitatsklinikum Essen, Essen, Germany.
13
Seoul St. Mary's Hospital, Seoul, South Korea.
14
Chuang Gung Memorial Hospital-Linko Branch, Taoyan County, Taiwan.
15
Universitatsklinikum Regensburg, Regensburg, Germany.
16
Universitatsklinikum Wurzburg, Wurzburg, Germany.
17
Indiana Blood and Marrow Transplantation-Clinic, Indiana, USA.
18
Stat4ward LLC, Pittsburgh.
19
USA Novartis Institutes for BioMedical Research, Massachusetts, USA.
20
USA Novartis Institutes for BioMedical Research, Massachusetts, USA florencia.segal@novartis.com.

Abstract

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 function 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 transplant. As would be expected in the study population, all patients (100%) reported at least one treatment-emergent adverse event. There were 22 deaths during this study and over 80% of 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 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 transplant. (ClinicalTrials.gov Identifier NCT02268526; EudraCT Number 2017-002047-15.).

PMID:
32015031
DOI:
10.1128/AAC.02467-19
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