RecruitingRecruiting
Study to Evaluate the Efficacy and Safety of Plitidepsin in Adults With Post-COVID-19 Condition (PCC)
NCT06766825 · Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
In plain English
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Official title
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)
About this study
Plitidepsin, a marine-derived cyclic depsipeptide that inhibits SARS-CoV-2 replication at nanomolar concentrations by targeting the host protein eukaryotic translation elongation factor 1A, could be a suitable candidate treatment for "Long COVID" because of a triple mechanism of action; a) it has demonstrated potent anti-SARS-CoV-2 in vitro activity, (b) it has a systemic anti-inflammatory effect, detailed in the text below, and (c) has an anti-herpes antiviral effect, which could provide additional therapeutic benefits to prevent herpesvirus reactivation seen in Long-COVID.
An interim analysis will be conducted upon reaching 30% and 50% of recruitment (patients treated with at least one dose and 28 days (+/- 2 days) of FUP)). The first interim analysis will focus exclusively on safety assessment, based on adverse events reported to date. The second interim analysis (50%) will evaluate safety and futility. A blinded safety report will be prepared, summarizing adverse events, and submitted to the Data Safety Monitoring Board (DSMB) for review and to determine whether to continue, modify, or terminate the study
Eligibility 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
Study design
Enrollment target: 90 participants
Allocation: randomized
Masking: triple
Age groups: adult, older_adult
Timeline
Starts: 2025-02-07
Estimated completion: 2026-09-01
Last updated: 2026-04-03
Interventions
Drug: Plitidepsin 1.5 mg/dayDrug: PlaceboDrug: Placebo and Plitidepsin 1.5mg/day
Primary outcomes
- • Change in the overall health in patients from each group using patient reported outcomes measurement information system score (PROMIS-29®). (On day 90 of follow-up period)
Sponsor
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia · other
With: PharmaMar, IrsiCaixa
Contacts & investigators
ContactLourdes Mateu Pruñonosa, phD, MD · contact · lmateu@lluita.org · +34 93 465 78 97
ContactCora Loste, phD, MD · contact · closte@lluita.org · +34 93 465 78 97
All locations (1)
Hospital Universitari Germans Trias i PujolRecruiting
Badalona, Barcelona, Spain