Fortress Biotech and its subsidiary Helocyte have initiated a Phase 2 clinical trial evaluating Triplex, a cytomegalovirus (CMV) vaccine, in hematopoietic stem cell transplant (HSCT) recipients. The multi-center, placebo-controlled, randomized trial is designed to assess the safety and efficacy of Triplex when administered to human leukocyte antigen (HLA) matched related stem cell donors, with the goal of reducing CMV events in patients undergoing HSCT.
The trial, funded by a grant from the National Cancer Institute (NCI), seeks to demonstrate the vaccine's ability to trigger a CMV-specific immune response in the donor. This immunity is then transferred to the transplant recipient through adoptive immunity, potentially offering earlier and more robust protection compared to vaccinating the recipient post-transplant.
Addressing CMV Reactivation Post-Transplant
CMV reactivation poses a significant threat to HSCT recipients. It is estimated that CMV reactivates in 60-70% of CMV-seropositive recipients and primary CMV infection occurs in 20-30% of CMV-seronegative recipients from CMV-seropositive donors. Current antiviral therapies, while effective in reducing CMV-related mortality, are associated with increased toxicity, delayed immune reconstitution, and late-onset CMV.
Don J. Diamond, Ph.D., Professor at City of Hope and principal investigator for the grant, emphasized the importance of this new approach: "CMV frequently affects patients undergoing transplants, posing significant risks to their recovery and survival. In this Phase 2 clinical trial, we are testing a new treatment approach, offering promise for better CMV management in HSCT recipients. This approach transfers CMV immunity from donors to transplant recipients, thereby potentially reducing the need for antiviral medications that can delay reconstitution of virus-specific immunity."
Trial Design and Locations
The Phase 2 trial (NCT03560752) is being conducted across three transplant centers in the United States: City of Hope in Duarte, California; Brigham & Women’s Hospital and Dana-Farber Cancer Institute in Boston; and Northside Medical Center in suburban Atlanta. The trial builds upon data from a Phase 1 pilot study, which evaluated the safety and immunological response of Triplex.
A subsequent NCI-funded trial will assess the same vaccine concept in higher-risk transplant recipients who are only partially HLA-matched to their donors, following a preliminary study in this transplant population (NCT04060277).
Triplex: A Novel Vaccine Approach
Triplex, originally developed by City of Hope and exclusively licensed to Helocyte, is a universal recombinant Modified Vaccinia Ankara viral vector vaccine. It is engineered to induce a robust and durable virus-specific T cell response to three immuno-dominant proteins [UL83 (pp65), UL123 (IE1), UL122 (IE2)] linked to CMV complications in the post-transplant setting.
Lindsay A. Rosenwald, M.D., Fortress’ Chairman and CEO and Executive Chairman of Helocyte, Inc., stated, "This new vaccination paradigm carries the advantage of potentially conveying earlier and more robust CMV immunity to a stem cell transplant recipient, versus vaccinating a HSCT recipient after engraftment has occurred around four weeks following transplant. We are very pleased that this trial is underway and believe that this novel treatment approach could play a significant role in the prevention and treatment of CMV in the future."
