Evaluating Plitidepsin for Adults with Long COVID

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)

Phase 2 Interventional Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia · NCT06766825

This study is testing if a new treatment called plitidepsin can help adults with long COVID feel better and improve their daily functioning.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment90 (estimated)
Ages18 Years and up
SexAll
SponsorFundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia Academic / other
Drugs / interventionsprednisone
Locations1 site (Badalona, Barcelona)
Trial IDNCT06766825 on ClinicalTrials.gov

What this trial studies

This study aims to assess the efficacy and safety of plitidepsin, a marine-derived compound, in treating adults suffering from post-COVID-19 condition (PCC). It is a randomized, double-blind trial involving 90 participants with moderate to severe functional disability, comparing plitidepsin to a placebo over a treatment period of approximately 135 days. Participants will receive intravenous infusions of plitidepsin or placebo every two weeks for four cycles, followed by a 90-day follow-up period to monitor outcomes. The study includes interim analyses to evaluate safety and treatment efficacy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older who have experienced symptoms of PCC for at least 90 days following a confirmed SARS-CoV-2 infection.

Not a fit: Patients who do not have a confirmed history of COVID-19 or those with alternative diagnoses explaining their symptoms may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the quality of life for patients suffering from Long COVID.

How similar studies have performed: While there have been studies exploring treatments for Long COVID, the specific use of plitidepsin represents a novel approach.

Eligibility criteria

Show full inclusion / exclusion criteria
1. Male or female individuals 18 years old or older.
2. 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. 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.
4. Unable to perform all usual duties/activities, defined as grades 3 or 4 in PCFS (Annex 3).
5. Willing to comply with the requirements of the protocol and available for follow-up for the planned duration of the study.
6. Having understood the information provided and capable of providing informed consent

EXCLUSION CRITERIA

1. Last SARS-CoV-2 vaccine dose during the previous 30 days.
2. Patients with active uncontrolled infections.
3. Patients infected by SARS-CoV-2 virus in the last 90 days prior to the screening visit.
4. Patients receiving treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers (Annex 1) throughout plitidepsin treatment period and until 24-h washout period.
5. Pacients receiving chronic glucocorticoid therapy (high-dose corticosteroids \[ie, 20 mg of prednisone daily or equivalent for ≥2 weeks)
6. Any of the following cardiac conditions or risk factors:

   * Cardiac infarction or cardiac surgery episode within the last six months 14
   * History of known congenital QT prolongation;
   * Known structural cardiomyopathy with abnormal left ventricular ejection fraction (LVEF) \<50%;
   * Current clinical evidence of heart failure or acute cardiac ischaemia (New York Heart Association (NYHA) class III-IV).
7. Hypersensitivity to the active ingredient or any of the excipients (mannitol, macrogolglycerol hydroxystearate, and ethanol) or contraindication to receive systemic glucocorticoids, antihistamine H1/H2 receptor agents, or antiserotonine 5HT3 receptors drugs.
8. Mast cell activation syndrome.
9. Females who are pregnant (negative serum or urine pregnancy test required for all females of childbearing potential at screening) or breast-feeding.
10. Females of childbearing potential (females who are not surgically sterile or postmenopausal defined as amenorrhea for \>12 months) who are not using highly effective contraceptive methods, while on study treatment and for 6 months after last dose of plitidepsin. Fertile males with partners of childbearing potential must use condom during treatment and for 6 months after last dose of plitidepsin. Refer to Annex 2 for contraception requirements.
11. Unable to consent and/or comply with study requirements, in the opinion of the investigator.
12. Currently participating or participated in a clinical trial within the prior

Where this trial is running

Badalona, Barcelona

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Post COVID-19 ConditionLong COVID SyndromePersistent COVID-19Persistent COVID ConditionLong COVIDSARS-CoV-2COVID-19Long COVID19
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.