The fourth and final cohort is dosing participants with the highest investigated dose of 3 x 106 cells/kg.
Tevogen Bio has initiated dosing in the fourth and final dose level of their phase 1 study (NCT04765449) of TVGN-489, an investigational, genetically unmodified SARS-CoV-2-specific cytotoxic CD8+ T lymphocyte therapy.1
“Given the observed safety profile of the last three cohorts, the Jefferson Health Institutional Review Board’s (IRB) Data & Safety Monitoring Committee has approved dose escalation to the fourth and final dosing level of TVGN-489,” principal investigator Dolores Grosso, DNP, CRNP, Jefferson University Hospitals, said in a statement.1
The open-label trial is assessing the T lymphocyte therapy in patients with COVID-19 and risk factors including diabetes, malignancies, hypertension, and chronic diseases, and/or being over the age of 65 years old. Treated participants are compared to patients receiving standard-of-care treatment. Enrollment is expected to conclude in the second quarter of 2022.
So far, 3 cohorts have dosed patients with 1 x 105 cells/kg, 3 x 105 cells/kg, or 1 x 106 cells/kg doses of TVGN-489. The fourth cohort is dosing participants with 3 x 106 cells/kg. Investigators have not observed any treatment-related AEs or dose-limiting toxicities, including cytokine release syndrome. All patients have also experienced lymphopenia correction.
Of note, patients in the first cohort were infected with the Delta variant, those in the second were infected with the Omicron BA.1 variant, and those in the third were infected with Omicron BA.2, BA.2.9, and BA.2.12.1 variants.
The trial is primarily assessing safety of TVGN-489 infusion via adverse events (AEs) and toxicities and secondary outcomes will explore COVID-related outcomes. These outcomes include viral load, COVID-19-specific T-cell persistence, endogenous COVID-19-specific T-cell development, and anti-COVID-19 antibodies, as well as medical history such as the need for supplemental oxygen, the ability to return to work, performance status, grade of dyspnea, grade of fatigue, survival, or the need for blood pressure support.
TVGN-489 is a highly purified, cytotoxic CD8+ T lymphocyte cell therapy designed to detect targets spread across the entire viral genome rather than only spike proteins. The company was granted a patent for their method of preparing and manufacturing TVGN-489 in January 2022.2
“Our next generation T cell technology maintains the promise of developing target-specific cell therapies in oncology, virology, and neurology for large patient populations without requiring specialized medical facilities. Additionally, I’m pleased to share that the company plans to study TVGN-489 for the prevention of Long COVID,” Ryan Saadi, MD, MPH, chief executive officer,Tevogen CEO, added to the statement.1