This is a Phase 2/3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of FP-025 in adult patients with severe to critical COVID-19 with associated ARDS. The patients in each phase (Phase 2 and Phase 3) will be analyzed separately. Each phase will consist of a Screening Visit, Treatment Period, and Follow-Up Period for a total study duration of approximately 60 days.~Phase 2: After eligibility is confirmed, approximately 90 patients will be randomized in a 1:1:1 ratio to receive FP-025 100 mg twice daily (BID), FP-025 300 mg BID, or placebo BID for 28 days. During Phase 2, randomized patients will be stratified by the use of invasive mechanical ventilation at the time of randomization (yes or no). At least one-third of patients should be on invasive mechanical ventilation to ensure that treatment benefits can be assessed for patients at different severity levels.~Patients with Grade 3 to Grade 4 heart failure, Stage 3 or greater chronic obstructive pulmonary disease, persistent asthma, and mild liver disease (ie, Child-Pugh Class A) will not be excluded from the study. The independent Data Monitoring Committee (iDMC) will independently monitor safety of the entire population and in different subgroups and may make recommendations as it deems appropriate. During Phase 2, no limitation in enrollment of subgroups is expected, unless clear safety signals arise in those subgroups during iDMC reviews.~The reason for hospital admission, the standard of care followed for each patient and center, and whether any care decisions were based on resource limitations will be clearly documented for all patients beginning on Day 1 (Visit 2). All patients will be allowed to receive standard of care and/or emergency use authorization (EUA) medications and treatment for COVID-19; however, the study drug should be discontinued for other non-standard of care concomitant medications used with the intent of directly treating COVID-19 unless there is prior Medical Monitor or Sponsor approval for the patient to remain on the study drug. If the use of concomitant medications necessitates study drug discontinuation, the patient should be encouraged to remain in the study and to follow-up for key study visits (Day 28 and Day 60) but will not be required to attend every study visit. If the patient withdraws, he/she should complete the Early Termination Visit.~Standard of care procedures for mechanical ventilation (eg, low tidal volume protective mechanical ventilation) and standard of care procedures for weaning from mechanical ventilation will be followed.~Study drug administration will begin on Day 1 (Visit 2) following randomization. All patients will receive standard of care and/or EUA treatment for COVID-19 in addition to the study drug. Patients will continue study drug treatment BID through Day 27 and take 1 dose on Day 28. If a patient is discharged from the hospital prior to Day 28, he/she will continue treatment as an outpatient at home with his/her assigned treatment (FP-025 100 mg BID, FP-025 300 mg BID, or placebo BID) until Day 28. Dosing instructions will be provided prior to discharge. Although treatment will be identical for inpatients and outpatients, patients discharged from the hospital will follow a different Schedule of Procedures, characterized by telemedicine (or telephone, if sites and/or patients do not have video capability) visits. The End of Treatment (EOT) Visit on Day 28 will be identical for all patients (with the exception of the arterial oxygen partial pressure [PaO2]/fractional inspired oxygen [FiO2] ratio, performed only in patients on invasive or non-invasive ventilation) and will include a high-resolution, non-contrast CT scan, in addition to other assessments.~After treatment is completed, all patients will undergo 2 follow-up assessments during the Follow-Up Period. The first follow-up will be a telephone visit on Day 45 to assess concomitant medications, adverse events (AEs), and the NIAID 8-point ordinal scale for COVID-19 and hospitalization outcomes score. The second follow-up will be an in-person visit on Day 60 and will include a high-resolution, non-contrast CT scan and pulmonary function tests, in addition to other assessments.~An iDMC will convene to oversee safety and efficacy assessments during and after the Phase 2 study. No formal statistical testing will be conducted. In addition, when all patients in the Phase 2 study have completed the EOT Visit on Day 28, a primary analysis will be conducted by an independent statistician and reviewed by the iDMC. This is the point at which the study was terminated, due to lack of further eligible patients.
This is a Phase 2/3, randomized, double blind, placebo controlled, multicenter study to evaluate the efficacy and safety of FP-025 in adult patients with severe to critical COVID 19 with associated ARDS.