Lori Panther (United States of America)
Moderna, Inc. Clinical DevelopmentPresenter of 1 Presentation
A PHASE 1, RANDOMIZED, OBSERVER-BLIND, PLACEBO-CONTROLLED, DOSE-RANGING STUDY TO EVALUATE THE SAFETY, REACTOGENICITY, AND IMMUNOGENICITY OF A MESSENGER RNA VACCINE AGAINST CYTOMEGALOVIRUS INFECTION (ID 371)
Abstract
Background
Cytomegalovirus is the most common congenital viral infection, with birth prevalence ranging 0.2-6.1% worldwide. We will present final safety and immunogenicity data from the Phase 1 trial of mRNA-1647, an mRNA-based vaccine encoding CMV pentamer complex (PC) and glycoprotein B (gB) antigens.
Methods
This Phase 1, first-in-human, randomized, placebo-controlled, dose-ranging study evaluated safety and immunogenicity of 30, 90, 180, or 300 ug of mRNA-1647 or placebo administered on a 0, 2, 6-month schedule through 12 months post 3rd vaccination in 154 healthy CMV-seronegative and CMV-seropositive adults 18-49 years old.
Results
A planned interim analysis at Month 12 (6 months post 3rd vaccination) indicated injection site pain (54-100%) as the most common solicited local adverse reaction (AR) over the 3-dose schedule across mRNA groups, and the most common solicited systemic ARs were headache (6-89%), fatigue (12-82%), myalgia (0-78%) and chills (6-82%). Antigen-specific antibody geometric mean titers (GMTs) increased with dose in both CMV-seronegative and CMV-seropositive groups. In the CMV-seronegative 30, 90, and 180 μg treatment groups, neutralizing antibody (nAb) GMTs against epithelial cell infection were ≥3.6-fold over the CMV-seropositive baseline GMT in the 90 μg and 180 μg treatment groups, and nAb GMTs against fibroblast infection approximated the CMV-seropositive baseline GMT in the 90 μg and 180 μg treatment groups. In CMV-seropositive treatment groups, nAb geometric mean ratios over baseline ranged between 14 and 31 against epithelial cell infection and between 6 and 8 against fibroblast infection.
Conclusions
This Phase 1 study showed mRNA-1647 to be generally well-tolerated. Vaccination with mRNA-1647 induced antigen-specific immune responses in CMV-seronegative participants and boosted immune responses in CMV-seropositive participants. This first-in-human trial demonstrates the potential of a mRNA vaccine to prevent CMV infection and supports its further development.
Clinical Trial Registration
ClinicalTrials.gov Identifier: NCT03382405