Triplex meets primary endpoint in phase 2 clinical trial, reduces rate of cytomegalovirus (CMV) complications in transplant recipients by 50 percent

Letisia Marquez 
First prophylactic vaccine to demonstrate proof of concept for CMV control independent of human leukocyte antigen (HLA) status in stem cell transplant recipients
DUARTE, Calif. — City of Hope, a world-renowned cancer research and treatment center, announced today that Triplex has met its primary endpoint (reduction of CMV events) in a phase 2 clinical trial evaluating the vaccine for control of CMV complications in hematopoietic stem cell transplant (HSCT) recipients. Triplex is a multi-antigen broadly recognized vaccine currently being developed for CMV control in stem cell and solid organ transplant recipients.
The multicenter, double-blind, placebo-controlled phase 2 trial was conducted at three major U.S.-based cancer centers: City of Hope, Dana-Farber Cancer Institute and MD Anderson Cancer Center. The trial enrolled 102 allogeneic HSCT recipients with matched related or unrelated donors who were randomized equally between vaccine and placebo arms. An independent data monitoring committee confirmed that Triplex was safe and well-tolerated with no significant difference in adverse events between arms.
In the trial, patients who received at least one injection of Triplex on day 28 after HSCT were observed to have 50 percent fewer CMV events (virus reactivation, antiviral treatment and disease) through day 100 than those who received placebo. There were five subjects with CMV events in the vaccine arm versus 10 in the placebo arm, one-sided time-to-event (p=0.08). The trial was designed to have 90 percent power at a one-sided significance level of 0.10 based on the Cox proportional-hazard model (time-to-event analysis), deemed appropriate for an initial phase 2 study.
“CMV is a major complication for many stem cell transplant recipients that can have severe health consequences,” said Ryotaro Nakamura, M.D., City of Hope associate professor in the Department of of Hematology & Hematopoietic Cell Transplantation, the trial’s principal investigator who presented the data at EBMT.
“This City of Hope-led trial demonstrates that Triplex is well tolerated and displayed potent immunogenicity, providing us with a potential powerful therapy against CMV,” said City of Hope’s Don J. Diamond, Ph.D., who invented the vaccine.
The Triplex phase 2 trial results were orally presented at the 45th Annual Meeting of the European Society for Blood and Marrow Transplantation in Frankfurt, Germany. Additional information, including the presentation abstract, “Multi-antigen vaccine (triplex) based on attenuated poxvirus prevents cytomegalovirus viremia in a multi-center placebo-controlled, double blinded, randomized phase 2 clinical trial in allogeneic HCT recipients,” can be accessed here.   
Triplex is a first-in-class, best-in-class, universal (non-HLA-restricted) recombinant modified vaccinia ankara viral vector vaccine engineered to induce a robust and durable virus-specific T cell response to three immuno-dominant proteins linked to CMV complications in the transplant setting: UL83 (pp65), UL123 (IE1) and UL122 (IE2). Helocyte Inc. is the exclusive licensee of Triplex, and provided support for the completion of the phase 2 trial.  Triplex was developed in partnership with the National Cancer Institute by its lead investigator, Diamond, of City of Hope. City of Hope acknowledges Bernard Moss, M.D., of the National Institute of Allergy and Infectious Disease, Laboratory of Viral Diseases, who provided materials. In a phase 1 study, Triplex was found to be safe, well-tolerated and highly immunogenic when administered to healthy volunteers at multiple dose levels ( Identifier: NCT01941056). Triplex is currently the subject of multiple ongoing and planned studies, one involving vaccination of the donor (followed by the recipient) in higher-risk stem cell transplant patients (NCT03560752), potentially introducing CMV immunity sooner and positioning Triplex ahead of prophylactic antivirals in the standard of care. The lifecycle of eligible patients is covered with an ongoing trial in pediatric HSCT patients (NCT03354728).
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About City of Hope
City of Hope is an independent biomedical research and treatment center for cancer, diabetes and other life-threatening diseases. Founded in 1913, City of Hope is a leader in bone marrow transplantation and immunotherapy such as CAR T cell therapy. City of Hope’s translational research and personalized treatment protocols advance care throughout the world. Human synthetic insulin and numerous breakthrough cancer drugs are based on technology developed at the institution. A National Cancer Institute-designated comprehensive cancer center and a founding member of the National Comprehensive Cancer Network, City of Hope is ranked one of America's "Best Hospitals" in cancer by U.S. News & World Report. Its main campus is located near Los Angeles, with additional locations throughout Southern California. For more information about City of Hope, follow us on FacebookTwitterYouTube or Instagram.