Moderna’s COVID-19 Vaccine Candidate Shows Safety, Immune Response Results in Phase 1 Study

July 15, 2020

Moderna announced interim analysis results of its investigational COVID-19 vaccine candidate, mRNA-1273, from an ongoing phase 1 study.

Moderna’s investigational vaccine candidate for the coronavirus disease 2019 (COVID-19) induced immune responses in all participants in its phase 1 study, according to new interim results from the ongoing trial.1

The findings reaffirm the positive interim data assessment that was reported on May 18. Moderna first launched human testing of the vaccine on March 16.

The open-label phase 1 study of mRNA-1273 evaluated a 2-dose vaccination schedule given 28 days apart across 3 dose levels (25, 100, 250 µg) in 45 healthy adult volunteers 18 to 55 years of age. Results were reported through day 57.1

According to the results, which were published in the New England Journal of Medicine, mRNA-1273 induced binding antibodies to the full length severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike protein (S) in all participants after the first vaccination, with all participants seroconverting by day 15. After the second vaccination, geometric mean titers exceeded those seen in convalescent sera obtained from 38 individuals with confirmed COVID-19 diagnosis. Of these individuals, 15% were classified as having severe symptoms, 22% had moderate symptoms, and 63% had mild symptoms.1

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The vaccine elicited robust neutralizing antibody titers after 2 vaccinations, the results showed. At day 43, neutralizing activity against SARS-CoV-2 was seen in all evaluated participants. At the 100 µg dose, the geometric mean titer levels were 4.1-fold above those seen in reference convalescent sera.1

Based on the findings from this analysis, mRNA-1273 was also shown to be generally safe and well tolerated, with no volunteers experiencing a serious adverse effect (AE) as a result. AEs that did occur were generally transient and mild-to-moderate in severity; more than half of participants reported mild-to-moderate reactions, such as fatigue, chills, headache muscles aches, or pain at the injection site. Additionally, solicited systemic AEs were more common after the second vaccination and occurred in 7 of the 13 participants in the 25 µg group, all 15 participants in the 100 µg group, and all 14 participants in the 250 µg group.1

The study investigators noted that the “rapid and robust immunogenicity profile of the mRNA01273 vaccine most likely results from an innovative structure-based vaccine antigen design, coupled with a potent lipid-nanoparticle delivery system, and the use of modified nucleotides that avoid early intracellular activation of interferon-associated genes.”1

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According to Moderna, evaluation of the durability of immune responses is ongoing. Participants will be followed for 1 year after the second vaccination.2

“These phase 1 data demonstrate that vaccination with mRNA-1273 elicits a robust immune response across all dose levels and clearly support the choice of 100 µg in a prime and boost regimen as the optimal dose for the phase 3 study,” Tal Zaks, MD, PhD, chief medical officer of Moderna, said in a statement.2 “We look forward to beginning our phase 3 study of mRNA-1273 this month to demonstrate our vaccine’s ability to significantly reduce the risk of COVID-19 disease.”

For the phase 3 COVE study, investigators plan to enroll 30,000 adult participants to test the 100 µg dose level of the vaccine. The target vaccine efficacy against COVID-19 for powering assumptions is 60%. Moderna expects enrollment into the study to begin late July.2

According to the company, it remains on track to be able to deliver approximately 500 million doses per year, and possibly up to 1 billion doses per year, beginning in 2021.2

References

1. Jackson LA, Anderson EJ, Rouphael NG, et al. An mRNA Vaccine against SARS-CoV-2–preliminary report. New England Journal of Medicine. July 14, 2020. Doi: 10.1056/NEJMoa2022483

2. Moderna Announces Publication in The New England Journal of Medicine of Interim Results From Phase 1 Study of Its mRNA Vaccine Against COVID-19 (mRNA-1273). News Release. Moderna; July 14, 2020. Accessed July 15, 2020. https://investors.modernatx.com/news-releases/news-release-details/moderna-announces-publication-new-england-journal-medicine