Phase II Proof-of-concept, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Plitidepsin in Adults with Post-COVID-19 Condition (PCC)
The study aims to prove that plitidepsin could be an efficacious, safe, and well-tolerated therapy for PCC. To this end, we will perform a randomized, double-blind study comparing the clinical and laboratory benefits of plitidepsin vs. placebo in 90 subjects with moderate to severe functional disability. The study consists of an intervention period and a follow-up period, with a total of 135 +/-3 days approximately between both periods. During the intervention period, four treatment cycles will be administered, scheduled every 15 days (every 2 weeks), with intravenous (IV) infusion over three consecutive days. After completing the intervention period, a 90-day (+/-5) follow-up period will be conducted. Subjects in arm A will receive the plitidepsin 1.5 mg/day 1h-IV during the four treatment periods on Days 1 to 3, Days 15 to 17, Days 29 to 31 and Days 43 to 45. Subjects in arm B will receive 1h-IV placebo 1 vial /day during the first two treatment periods and will receive the plitidepsin 1.5 mg/day 1h-IV during the last two treatment periods. Subjects in arm C will receive 1h-IV placebo 1 vial/day during the four treatment periods.
• Male or female individuals 18 years old or older.
• Evidence of SARS-CoV-2 infection at least 90 days prior to study recruitment, defined by either (a) nasopharyngeal SARS-CoV-2 nucleic acid test \[polymerase chain reaction (PCR) or transcription mediated amplification (TMA)\], (b) validated Nasopharyngeal Lateral Flow Assay rapid antigen test (RAT), or (c) or positive serology against SARS-CoV-2 N protein regardless vaccination status.
• 3 or more symptoms of PCC affecting at least two organs, after 90 days from the onset of SARS-CoV2 infection and that last for at least 2 months and cannot be explained by an alternative diagnosis. Symptoms may be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms may also fluctuate or relapse over time.
• Unable to perform all usual duties/activities, defined as grades 3 or 4 in PCFS (Annex 3).
• Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study.
• Having understood the information provided and capable of providing informed consent