Triplex is a universal (non-HLA-restricted) vaccine engineered to induce a virus-specific T-cell response to control CMV in recipients of allogeneic hematopoietic stem cell transplant (“HSCT”) and solid organ transplant (“SOT”) recipients. To our knowledge, Triplex is the only vaccine in clinical development incorporating a recombinant viral vector with genes expressing three immuno-dominant proteins linked to CMV in the post-transplant setting [e.g., UL83 (pp65), UL123 (IE1), UL122 (IE2)]. The vaccine is comprised of the Modified Vaccinia Ankara (MVA) vector, which has been dosed safely in over 120,000 patients (young and old) and has been shown to be prolifically expressed and highly immunogenic. A recent study further demonstrated that use of MVA was safe in HSCT recipients (for more information, see
http://www.ncbi.nlm.nih.gov/pubmed/23482644). Triplex is being developed for control of CMV in allogeneic HSCT and SOT recipients. Triplex was recently investigated in a Phase 1b dose-escalation study in 24 healthy volunteers at three dosing levels conducted at a single site, City of Hope National Medical Center in Duarte California. Patients received two intermuscular injections of Triplex vaccine four weeks apart starting on Day 28 after transplant. The study demonstrated that Triplex is both safe and highly immunogenic, inducing robust expansion of CD4+ and CD8+ T-cells specific for each immuno-dominant CMV protein. More specifically, healthy volunteers receiving Triplex showed robust and durable post-vaccination increases in CMV pp65-, IE1- and IE2-specific T-cells. CMV-specific T-cell responses were particularly pronounced in CMV-seropositive healthy volunteers with low pre-vaccination levels of CMV-specific T-cells. The results of the Triplex Phase 1b study were accepted for poster presentation at the 2015 Annual Meeting of the American Society of Hematologists (“ASH”). The ASH abstract for the Triplex Phase 1b can be accessed at https://ash.confex.com/ash/2015/webprogram/Paper81450.html.
Based on the encouraging safety and imunogenicity data generated in the aforementioned Phase 1b, Helocyte commenced a multi-center, randomized (1:1), double-blinded, placebo-controlled Phase 2 study of Triplex in 96 HSCT CMV-seropositive recipients who will receive two intermuscular injections (on Days 28 and 56 respectively). The primary endpoint is CMV reactivation through Day 100 as monitored by PCR, and we plan to study other related endpoints such as CMV-specific T-cell response, duration of viremia, time on antivirals, graft versus host disease and relapse-free survival. The Phase 2 study is supported by grants from the National Cancer Institute. GMP-grade clinical materials have already been manufactured in sufficient quantity to complete the Phase 2 study. We plan to additionally study the use of Triplex in control of CMV in allogeneic SOT recipients. For more information regarding the Phase 2 study of Triplex in Recipients of Allogeneic HSCT, see https://clinicaltrials.gov/ct2/show/NCT02506933?term=triplex+cmv&rank=1.