CAMBRIDGE, Mass.—Moderna, Inc. has reported positive interim clinical data of mRNA-1273, the company’s vaccine candidate against SARS-CoV-2, from the Phase 1 study led by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.
Immunogenicity data are currently available for the 25 µg and 100 µg dose level (ages 18-55) after two doses (day 43), and at the 250 µg level (ages 18-55) after one dose (day 29). Dose dependent increases in immunogenicity were seen across the three dose levels, and between prime and boost within the 25 µg and 100 µg dose levels. All participants ages 18-55 (n=15 per cohort) across all three dose levels seroconverted by day 15, after a single dose.
At day 43, two weeks after the second dose, levels of binding antibodies at the 25 µg dose level (n=15) were at the levels seen in convalescent sera (blood samples from those who have recovered from COVID-19) tested in the same assay. At day 43, at the 100 µg dose level (n=10), levels of binding antibodies significantly exceeded the levels seen in convalescent sera. Samples are not yet available for the remaining participants.
“These interim Phase 1 data, while early, demonstrate that vaccination with mRNA-1273 elicits an immune response of the magnitude caused by natural infection starting with a dose as low as 25 µg,” said Tal Zaks, M.D., Ph.D., chief medical officer of Moderna. “When combined with the success in preventing viral replication in the lungs of a preclinical challenge model at a dose that elicited similar levels of neutralizing antibodies, these data substantiate our belief that mRNA-1273 has the potential to prevent COVID-19 disease and advance our ability to select a dose for pivotal trials.”
At this time, neutralizing antibody data are available only for the first four participants in each of the 25 µg and 100 µg dose level cohorts. Consistent with the binding antibody data, mRNA-1273 vaccination elicited neutralizing antibodies in all eight participants, as measured by plaque reduction neutralization assays against live SARS-CoV-2. The levels of neutralizing antibodies at day 43 were at or above levels generally seen in convalescent sera.
mRNA-1273 was generally safe and well tolerated, with a safety profile consistent with those seen in prior Moderna infectious disease vaccine clinical studies. The sole incidence of a grade 3 adverse event in the 25 µg and 100 µg dose cohorts was a single participant at 100 µg who experienced grade 3 erythema around the injection site. To date, the most notable adverse events were seen at the 250 µg dose level, comprising three participants who experienced grade 3 systemic symptoms following the second dose. All adverse events were been transient and self-resolving. No grade 4 adverse events or serious adverse events have been reported.
Preclinical results are also available from a viral challenge study in mice, conducted in collaboration with the NIAID and its academic partners. In this study, vaccination with mRNA-1273 prevented viral replication in the lungs of animals challenged with SARS-CoV-2. Neutralizing titers in Phase 1 clinical trial participants at the 25 µg and 100 µg dose levels were consistent with neutralizing titers that were protective in the mouse challenge model.
“With today’s positive interim Phase 1 data and the positive data in the mouse challenge model, the Moderna team continues to focus on moving as fast as safely possible to start our pivotal Phase 3 study in July and, if successful, file a BLA. We are investing to scale up manufacturing so we can maximize the number of doses we can produce to help protect as many people as we can from SARS-CoV-2,” noted Stéphane Bancel, chief executive officer of Moderna.
Based on the interim Phase 1 data, the Moderna-led Phase 2 study will be amended to study two dose levels — 50 µg and 100 µg — with the aim of selecting a dose for pivotal studies. The NIAID-led Phase 1 study is being amended to include a 50 µg dose level cohort across each of the three age groups. Moderna anticipates that the dose for the Phase 3 study will be between 25 µg and 100 µg, and expects to finalize study protocol and initiate a Phase 3 trial in July.