Investigational mRNA CMV Vaccine Ready for Phase 3 Clinical Trial, Based on Results of Phase 2 Safety, Efficacy and Dose-Finding Study

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The investigational mRNA-based vaccine mRNA-1647 against cytomegalovirus (CMV) was found safe and well tolerated in healthy adults in a phase 2 randomized dose-finding trial,¹ results of which were reported on Saturday at IDWeek, taking place in Boston October 11-15, 2023.

The findings will support the vaccine dose to be used in the upcoming phase 3 registration trial for mRNA1647.¹

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CMV is a latent virus that endures in the body after infection and in adults, most of whom are infected by the age of 40 years, typically goes undetected.² For individuals with immunocompromise or infants born with the infection, consequences can be serious. Congenital CMV is the leading infectious cause of birth defects in the US. Currently there is no approved vaccine to prevent CMV.²

The mRNA-1647 vaccine is comprised of 6 specific mRNA sequences that encode for 2 key CMV antigens. The current phase 2 trial (NCT04232280), which was randomized, observer-blind, and placebo-controlled, was conducted in healthy adults aged 18 to 40 years divided into cohorts of CMV-seronegative and CMV-seropositive participants, according to the study. It comprised 2 parts.¹

In Part 1, men and women were randomly assigned in a 3:1 ratio to receive mRNA-1647 (50, 100, or 150 µg) or placebo at months 0, 2, and 6 of the study.

In Part 2, women only were randomly assigned, again in a 3:1 ratio, to receive mRNA-1647 100 µg or placebo at study months 0, 2, and 6.

Investigators had 2 primary endpoints of interest: safety throughout the study, which included solicited adverse events up to 7 days after receipt of each dose of mRNA-1647; and neutralizing antibody (nAB) titers against both epithelial cell and fibroblast infection up to 12 months after the last study dose.

According to the study, the results were combined for both parts.

RESULTS¹

Safety. The full cohort numbered 315 participants. Among the seronegative participants, researchers reported that 54.7% of those receiving placebo reported solicited adverse events after the first dose as did 84.4% who received a 50-µg dose, 87.5% receiving a 100-µg dose, and 91.1% receiving a 150-µg dose of mRNA-1647. Among the CMV-seropositive participants, solicited adverse events were reported by 59.3% (placebo), 94.4% 50 µg), 94.6% (100 µg), and 94.4% (150 µg).

The trends observed in adverse events were similar after the second and third doses, study authors said.

After dose 1, across serostatus groups, the most common local solicited adverse event was pain (mRNA-1647, 73.3%-89.2%; placebo, 18.5%-18.9%) and the corresponding most common systemic event was fatigue (mRNA-1647, 28.9%-72.2%; placebo, 25.9%-30.2%).

Efficacy. All treatment groups exhibited nAB titers against epithelial cell infection and against fibroblast infection. The nAB responses against epithelial cell infection were strong after each mRNA-1647 dose and were sustained through 12 months following the last dose, according to the study abstract.

The investigators reported that nAB titers against epithelial cell infection in CMV-seronegative participants who received the mRNA1647 100-µg dose was greater than the geometric mean titer of all the CMV-seropositive recipients at baseline.

Dose. The findings that mRNA-1647 was generally safe and well-tolerated and induced antigen-specific immune responses at all dose levels in both CMV-seronegative and -seropositive participants, the researchers wrote, guided selection of the 100-µg dose for the mRNA-1647 phase 3 trial.

The phase 3 study, known as CMVictory, will evaluate the safety and efficacy of mRNA-1647 against primary CMV infection in women aged 16-40 years.² According to Moderna, the company investigating mRNA-1647, the plan is to enroll approximately 8000 participants, including 6900 women of childbearing age, from approximately 150 sites globally. The company has set a goal of creating a diverse group of participants in the US, including approximately 42% from racial and ethnic minorities.²

References:

1. Panther L, Basnet S, Fierro C, et al. Safety and immunogenicity of mRNA-1647, an mRNA-based cytomegalovirus vaccine in healthy adults: results of a phase 2, randomized, observer-blind, placebo-controlled, dose-finding trial. Abstract presented at IDWeek 2023; October 11-15, 2023; Boston, MA. 2. Moderna announces first participant dosed in phase 3 pivotal registration study of its mRNA cytomegalovirus (CMV) vaccine. News release. Moderna. October 26, 2021. Accessed October 11, 2023. https://investors.modernatx.com/news/news-details/2021/Moderna-Announces-First-Participant-Dosed-in-Phase-3-Pivotal-Registration-Study-of-Its-mRNA-Cytomegalovirus-CMV-Vaccine/default.aspx

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