112. Interim Results From a Phase 2, Randomized, Observer-Blind, Placebo-Controlled, Dose-Finding Trial of an mRNA-Based Cytomegalovirus Vaccine in Healthy Adults

Abstract

Abstract Background Cytomegalovirus (CMV) is the most common congenital viral infection and can cause severe long-term health consequences, including hearing loss and neurodevelopmental delay. A safe and effective method for prevention of CMV infection is an unmet need and public health priority. An mRNA-based vaccine against CMV, mRNA-1647, is in development and consists of 6 mRNA sequences encoding 2 CMV antigens (glycoprotein B and the pentameric glycoprotein complex) in a lipid nanoparticle formulation. Methods In this Phase 2, randomized, placebo-controlled, observer-blind, dose-finding trial, safety and immunogenicity of mRNA-1647 was evaluated in healthy adults aged 18 to 40 years (NCT04232280). In Part 1, CMV-seronegative and CMV-seropositive men and women were randomized 3:1 to receive mRNA-1647 (doses of 50, 100, or 150 µg) or placebo at Months 0, 2, and 6. The 100-µg dose was chosen for Part 2. In Part 2, CMV-seronegative and CMV-seropositive women were randomized 3:1 to receive mRNA-1647 100 µg or placebo at Months 0, 2, and 6. Safety endpoints were solicited local and systemic adverse reactions, unsolicited adverse events (AEs), and medically attended AEs through 7 days, 28 days, and 6 months after vaccination, respectively, and serious AEs throughout the study. Humoral immunogenicity endpoints were antigen-specific binding antibody titers and neutralizing antibody titers against epithelial cell infection and against fibroblast infection. Results In Parts 1 and 2, 252 and 63 participants were randomized, respectively. Interim analysis (IA) of Part 1 through 1 month after Dose 3 indicated that mRNA-1647 100 µg was generally well-tolerated, induced robust antibody responses in CMV-seronegative participants, and boosted antibody titers in CMV-seropositive participants. An additional IA of Part 1 through end of study and Part 2 through 1 month after Dose 3 showed no notable differences in the safety profile compared with the previous IA (Part 1, 1 month after Dose 3); immunogenicity data for this additional IA is being generated. Conclusion Available data from this Phase 2 trial suggest that mRNA-1647 100 µg was immunogenic in CMV-seronegative and CMV-seropositive participants and was generally well-tolerated. The mRNA-1647 candidate vaccine is being evaluated in a Phase 3 trial. Disclosures Lori Panther, MD, MPH, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Richard Leggett, DO, Crossroads Clinical Research: Contract employee James Peterson, MD, Moderna, Inc.: Received payment as a study investigator Jiang Lin, PhD, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Kai Wu, PhD, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Heather Lee, BS, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Roxane Hasselbeck, BA, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Andrew Natenshon, MA, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Jacqueline Miller, MD, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds.