Moderna finalizes design of phase 3 COVID-19 vaccine trial ahead of July start

Moderna has finalized the design and dosage of its phase 3 COVID-19 vaccine trial, keeping it on track to start the pivotal test next month. Work to get the 30,000-subject phase 3 trial underway is advancing in parallel to ongoing enrollment in earlier phases of development.

Messenger RNA biotech Moderna set out its expectations for the phase 3 trial when it shared a first glimpse at clinical data on its mRNA-1273 vaccine last month. At that time, Moderna expected the phase 3 trial to test a dose between 25 µg and 100 µg, reflecting the adverse events seen in the 250-µg cohort, and get underway in July.

Moderna looks set to hew closely to those proposals. Having spoken to the FDA, Moderna plans to randomize 30,000 people in the U.S. on a one-to-one basis to receive either 100 µg of mRNA-1273 or placebo. 

The primary objective of the trial, which is set to start in July, is to assess the ability of mRNA-1273 to prevent symptomatic COVID-19 disease. Secondary endpoints will assess the ability of mRNA-1273 to prevent hospitalization and infection with SARS-CoV-2.

Ideally, the vaccine will stop people from catching and transmitting SARS-CoV-2. However, preclinical data on the vaccine the University of Oxford is developing with AstraZeneca raised the prospect that some of the candidates in development may be able to stop severe COVID-19 cases but not prevent the spread of the virus.

Moderna has shared data on the effects of its vaccine in eight phase 1 trial participants to date. In picking the mix of primary and secondary endpoints, Moderna has positioned the phase 3 to detect several different signs of efficacy. Depending on the endpoints Moderna hits, mRNA-1273 may fall short of what the world wants from a COVID-19 vaccine but still be a useful tool in protecting people and healthcare systems from the most devastating effects of the virus.

The nature of the endpoints means it is unclear when Moderna will have phase 3 data. As the three key endpoints are driven by SARS-CoV-2 infections, the extent to which participants are exposed to the virus will dictate how quickly the trial shows whether mRNA-1273 is helping.

Moderna is continuing to enroll participants in the phase 1 and 2 trials. The phase 1, which showed Moderna that 100 µg is the optimal dose, is still enrolling subjects in three cohorts. Enrollment in the first, 300-subject cohort of the phase 2 is now complete, 13 days after the dosing of the first subject. Moderna has also fully enrolled a sentinel cohort of 50 people aged 55 years and older. If the vaccine looks safe in that population, Moderna will go on to enroll 300 people aged 55 years and older.

All participants will receive either placebo or a 50-µg or 100-µg shot of mRNA-1273. Moderna will give each participant two shots 28 days apart and follow them for 12 months after the second dose.