TVGN-489 is an investigational allogeneic cytotoxic CD8+ T lymphocyte therapy that may help prevent breakthrough COVID infection.
Tevogen Bio and Thomas Jefferson University are beginning enrollment of their phase 1 trial (NCT04765449) for TVGN-489 for the treatment of high-risk patients with COVID-19.
TVGN-489 is an investigational allogeneic SARS-CoV-2 specific Cytotoxic CD8+ T lymphocytes (CTL) therapy designed to protect against breakthrough COVID infection and hospitalization in high-risk patients, whether due to age or other underlying health conditions. TVGN-489 previously demonstrated its ability to target and destroy infected cells in preclinical studies.
"This trial will evaluate whether this therapy is safe and effective in eliminating the virus in infected high-risk patients. We are optimistic that, because TVGN-489 is designed to attack a variety of targets across the SARS-CoV-2 genome, the therapy will be effective against rapidly emerging variants, such as the Delta strain," said principal investigator, Dolores Grosso, DNP, Jefferson Health, in a statement.
The study plans to enroll 24 participants with COVID-19 that are elderly or high-risk. Participants with an HLA antigen in common with COVID-19 fighting T cells will receive a single infusion of TVGN-489. The control group will not receive any CTLs. Both groups will be monitored for adverse events (AEs) and outcomes.
Four dose levels of CTLs will be evaluated: 1 x 105/kg, 3 x 105/kg, 1 x 106/kg, and 3 x 106/kg, with groups of 3 to 6 patients receiving each ascending dose pending no serious AEs. Each patient will be monitored for 14 days before the next patient can be treated.
"We are very excited to announce the start of this trial. We believe this work will harness Jefferson University's unparalleled expertise and research prowess to investigate TVGN-489 as a vital tool in the fight against COVID-19," Ryan Saady, MD, MPH, chief executive officer, Tevogen, added to the statement.
The study’s primary outcomes are focused on safety and will assess infusion reactions, grade 4 AEs, graft-versus-host-disease, marrow aplasia, neurotoxicity, and cytokine release syndrome within 14 days of infusion. Secondary efficacy outcomes will assess COVID-19 viral load within 14 days or infusion, as well as longer term outcomes such as persistence of COVID-19-specific T cells, development of endogenous COVID-19 specific T cells, development of anti-COVID-19 antibodies, and any notable medical events within up to 6 months of infusion.
"CTLs are the tools normally used by our bodies to eliminate viral infections. Current COVID-19 treatments attempt to slow the virus until our own CTLs can develop in adequate numbers to eliminate the infection. In contrast, TVGN-489 provides substantial numbers of highly enriched, highly potent SARS-CoV-2 specific CTLs directly to the patients. It is because we are using nature's own tools that we are optimistic that this approach will prove both safe and effective," Neal Flomenberg, MD, professor and chair, department of medical oncology, and director, blood and marrow transplant program, Thomas Jefferson University, added to the statement.
The news follows the FDA’s approval of the Pfizer-BioNTech COVID-19 vaccine, BNT162b2 (Comirnaty) in August 9 months after it originally received emergency use authorization. The vaccine became the first to be FDA-approved.