Gilead Sciences has made major mid-study changes to its global remdesivir trials, quadrupling the enrollment target and switching the primary endpoint. The changes come as the world waits for results from the Chinese clinical trials of the advanced COVID-19 antiviral candidate.
Remdesivir’s position at the front of the pack of potential COVID-19 drugs and vaccines has made it a very closely watched therapeutic. In that heightened environment, any information about the drug and its development is being scrutinized for hints about whether the therapy is likely to work, making Gilead’s updates to its ClinicalTrials.gov listings notable events.
The updates detail significant changes. Across the two open-label trials, Gilead set out to enroll 1,000 patients with moderate or severe COVID-19. The primary endpoint of the trial of moderate COVID-19 patients originally looked at the proportion of patients discharged by day 14. The trial of severe patients was assessing the normalization of fever and oxygen saturation through day 14.
Now, Gilead has changed all of those details. The trial of patients with severe COVID-19 has swelled in size from 400 subjects to 2,400 participants. Gilead dialed the enrollment target in the clinical trial of moderate COVID-19 patients up from 600 to 1,600.
The trials have new primary endpoints, too. In each case, Gilead has changed the primary endpoint to focus on the odds of improvement on a seven-point scale that runs from death to not hospitalized.
Gilead will enroll the additional patients in new arms it just added to the study. Both trials feature a spillover arm that will take in subjects after enrollment in the original part of the study is complete. The trial targeting patients with severe COVID-19 also features a second additional arm.
Having initially only enrolled participants who had severe disease but were yet to need mechanical ventilation, Gilead has now added a cohort of mechanically ventilated patients. People enrolled in the new cohort will receive a 10-day regimen of remdesivir, the longer of the two dosing schedules being assessed in the phase 3 trials.
What, if anything, the changes mean for the prospects of remdesivir is unclear. A skeptic could read the increased enrollment targets and change of primary endpoints as evidence of concerns that the studies lacked the power to detect improvements associated with remdesivir. Equally, Gilead’s willingness to add mechanically ventilated patients to the severe study could be interpreted as a sign of confidence.
The situation will only become clearer once researchers start publishing data from clinical trials of the antiviral. With results from Chinese trials of remdesivir due imminently, the wait for those data is now nearing an end. According to Evercore ISI analyst Umer Raffat, if it takes 16 days for patients on placebo to improve, remdesivir will need to cut the time to improvement to 13 days for the clinical trial to achieve statistical significance.