Post COVID-19 ConditionPhase 2THALASSANCT06766825
Study to Evaluate the Efficacy and Safety of Plitidepsin in Adults With Post-COVID-19 Condition (PCC)
A Phase 2 study testing Plitidepsin 1.5 mg/day in people with Post COVID-19 Condition and Long COVID Syndrome, run by Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia at 1 site in Spain.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Post COVID-19 Condition, Long COVID Syndrome, Persistent COVID-19
- What is being tested?
- Plitidepsin 1.5 mg/day
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 1 siteSpain
- Study dates
- 7 Feb 2025to 29 Sep 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Last SARS-CoV-2 vaccine dose during the previous 30 days.
- Patients with active uncontrolled infections.
- Patients infected by SARS-CoV-2 virus in the last 90 days prior to the screening visit.
- Patients receiving treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers (Annex 1) throughout plitidepsin treatment period and until 24-h washout period.
- Pacients receiving chronic glucocorticoid therapy (high-dose corticosteroids [ie, 20 mg of prednisone daily or equivalent for ≥2 weeks)
- Any of the following cardiac conditions or risk factors:
Show all 16Show fewer
- 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).
- 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.
- Mast cell activation syndrome.
- Females who are pregnant (negative serum or urine pregnancy test required for all females of childbearing potential at screening) or breast-feeding.
- 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.
- Unable to consent and/or comply with study requirements, in the opinion of the investigator.
- Currently participating or participated in a clinical trial within the prior
Trial locations and contacts
1 site in 1 country.
Spain1 site
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, 08916
About this study
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)
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.
Read the detailed description
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
- Conditions
- Post COVID-19 Condition, Long COVID Syndrome, Persistent COVID-19, Persistent COVID Condition, Long COVID
- Being tested
- Plitidepsin 1.5 mg/day, Placebo, Placebo and Plitidepsin 1.5mg/day
- Keywords
- SARS-CoV-2, COVID-19, Long COVID19, Plitidepsin
- Medical subject headings
- Post-Acute COVID-19 Syndrome, COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Plitidepsin 1.5 mg/dayDrug
Receive 1.5 mg/day of plitidepsin intravenously (IV) over a 1-hour infusion for 3 consecutive days every 15 days during 4 treatment periods.
The participant will receive the following pre-medication before receiving the study treatment:
- Palonosetron 0.25 mg IV
- Dexchlorpheniramine maleate 5 mg IV (or equivalent to H1 receptor antihistamines)
- Famotidine 40 mg oral (60 minutes before starting the plitidepsin/placebo infusion)
- Dexamethasone phosphate 8 mg IV (equivalent to 6.6 mg of dexamethasone)
Premedication should be completed 20-30 minutes before starting the plitidepsin/placebo infusion.
PlaceboDrug
Receive placebo intravenously (IV) over a 1-hour infusion for 3 consecutive days every 15 days during 4 treatment periods.
The participant will receive the following pre-medication before receiving the study treatment:
- Palonosetron 0.25 mg IV
- Dexchlorpheniramine maleate 5 mg IV (or equivalent to H1 receptor antihistamines)
- Famotidine 40 mg oral (60 minutes before starting the plitidepsin/placebo infusion)
- Dexamethasone phosphate 8 mg IV (equivalent to 6.6 mg of dexamethasone)
Premedication should be completed 20-30 minutes before starting the plitidepsin/placebo infusion.
Placebo and Plitidepsin 1.5mg/dayDrug
Receive placebo intravenously (IV) over a 1-hour infusion for 3 consecutive days every 15 days during two treatment periods and receive plitidepsin 1.5mg/day during the last two treatment periods.
The participant will receive the following pre-medication before receiving the study treatment:
- Palonosetron 0.25 mg IV
- Dexchlorpheniramine maleate 5 mg IV (or equivalent to H1 receptor antihistamines)
- Famotidine 40 mg oral (60 minutes before starting the plitidepsin/placebo infusion)
- Dexamethasone phosphate 8 mg IV (equivalent to 6.6 mg of dexamethasone)
Premedication should be completed 20-30 minutes before starting the plitidepsin/placebo infusion.
| Study group | Role | What they receive |
|---|---|---|
| A. Plitidepsin Arm | Experimental | 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. Receives: Drug: Plitidepsin 1.5 mg/day |
| B. Placebo/Plitidepsin | Experimental | Subjects in arm B will receive 1h-IV placebo 1 vial /day during the first two treatment periods (Days 1 to 3 and Days 15 to 17) and plitidepsin 1.5 mg/day 1h-IV during the last two treatment periods (Days 29 to 31 and Days 43 to 45). Receives: Drug: Placebo and Plitidepsin 1.5mg/day |
| C. Placebo Arm | Placebo comparator | Subjects in arm C will receive 1h-IV placebo 1 vial/day during the four treatment periods on Days 1 to 3, Days 15 to 17, Days 29 to 31, and Days 43 to 45. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in the overall health in patients from each group using patient reported outcomes measurement information system score (PROMIS-29®).
Difference between groups on the patient-reported outcomes measurement information system (PROMIS-29®) score health scale measured by T-Score; Each domain is scored on a 5-point scale, (without any difficulty, with a little difficulty, with some difficulty, with much difficulty, unable to do), in case of the pain domain is on a 10-point scale; from no pain to the worse pain. on day 90 (±5) of the follow-up period* (after the intervention).
Measured: On day 90 of follow-up period
Secondary outcomes (28)
To compare the safety/tolerability of Plitidepsin Vs placebo in terms of adverse events in patients with PCC.
The proportion of adverse events (AE, coded by MedDRA) comparing between groups at day 90 (±5) of the follow-up period, considering:
- All AEs.
- AEs grade 3 and 4 leading to discontinuation from the study.
- AEs of special interest (AESI): cardiac, liver, acute-infusional reactions.
Measured: On day 90 of follow-up period
To compare the incidence of Treatment-Emergent Adverse Events (TEAEs) between groups.
Percentage of TEAEs detected on day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.
Measured: On day 10, day 30 and day 90 of follow-up period
To compare changes in the overall health in patients from each group using patient reported outcomes measurement information system score (PROMIS-29®).
Difference between groups on the PROMIS-29® health scale measured by T-Score on day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period. Each domain is scored on a 5-point scale, (without any difficulty, with a little difficulty, with some difficulty, with much difficulty, unable to do), in case of the pain domain is on a 10-point scale; from no pain to the worse pain. on day 90 (±5) of the follow-up period* (after the intervention).
Measured: On day 10, day 30 and day 90 of follow-up period
To compare functional capacity changes in patients from each group using the post-COVID-19 Functional State (PCFS) scale.
Difference between groups in functional capacity on the PCFS scale on day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.
Measured: On day 10, day 30 and day 90 of follow-up period
To compare symptomatic changes in patients from each group using the Can Ruti Questionnaire.
Proportion of subjects with ≥10 points reduction in the Can Ruti Questionnaire scale on day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.
Measured: On day 10, day 30 and day 90 of follow-up period
To compare changes in terms of Quality of Life (QoL) for each group.
Difference between groups according to the EuroQoL-5D questionnaire on day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.
Measured: On day 10, day 30 and day 90 of follow-up period
To compare neuropsychological symptomatology [psychomotor speed and executive function] in patients with PCC among the three treatment arms.
Change from baseline** in neuropsychological symptoms to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period, measured using NeuScreen questionnaire to evaluate the psychomotor speed and executive function measured in seconds.
Measured: On day 10, day 30 and day 90 of follow-up period
To compare neuropsychological symptomatology [depressive symptoms] in patients with PCC among the three treatment arms.
Change from baseline** in neuropsychological symptoms to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period, using the PHQ-9 score questionnaire to evaluate the depressive symptoms, each question is scored on a 4-point scale, where (0) is the most positive answe and (3) is the worse condition.
Measured: On day 10, day 30 and day 90 of follow-up period
To compare neuropsychological symptomatology [ anxiety symptoms] in patients with PCC among the three treatment arms.
Change from baseline** in neuropsychological symptoms to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period, using the GAD-7 questionnaire to evaluate anxiety symptoms; Each question is scored as follows: 0 points: "Not at all", 1 point: "Several days", 2 points: "More than half the days", 3 points: "Nearly every day"
Measured: On day 10, day 30 and day 90 of follow-up period
To compare neuropsychological symptomatology [sleep quality] in patients with PCC among the three treatment arms.
Change from baseline** in neuropsychological symptoms to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period, measured using PSQI to evaluate sleep quality; the scores for the seven components are then summed to yield a global PSQI score, which ranges from 0 to 21. A global score greater than 5 suggests poor sleep quality.
Measured: On day 10, day 30 and day 90 of follow-up period
To compare neuropsychological symptomatology [disability] in patients with PCC among the three treatment arms.
Change from baseline** in neuropsychological symptoms to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period, using WHODAS 2.0 questionnaire to evaluate disability: Each item is scored on a scale from 1 to 5, with higher scores indicating greater difficulty in functioning. The total score is calculated by summing the scores for all items, and it can be converted into a standardized score ranging from 0 to 100, where higher scores indicate greater disability.
Measured: On day 10, day 30 and day 90 of follow-up period
To compare changes in terms of physical activity in patients with PCC among the three arms.
Change from baseline in physical activity to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period, assessed using the International Physical Activity Questionnaire (IPAQ).
Measured: On day 10, day 30 and day 90 of follow-up period
To compare changes in terms of fatigue (Fatigue scale) in patients with PCC among the three treatment arms.
Change from baseline in physical activity to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period, evaluated using the Fatigue Severity Scale (FSS): nine statements, of 7-point Likert scale, where (1- Strongly disagree) and (7-Strongly agree). Higher scores indicate greater fatigue severity.
Measured: On day 10, day 30 and day 90 of follow-up period
To compare changes in terms of fatigue (Five times sit to stant test) in patients with PCC among the three treatment arms.
Change from baseline in physical activity to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period, evaluated using Five Times Sit-to-Stand Test (5xSTS), The score is the total time in seconds
Measured: On day 10, day 30 and day 90 of follow-up period
To compare the evolution of inflammation markers in patients with PCC among the three arms.
Change from baseline in inflammation markers on day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.
Measured: On day 10, day 30 and day 90 of follow-up period
To compare immune response markers: Antinuclear antibodies (ANAs) in patients with persistent COVID among the three treatment arms.
Change from baseline in Antinuclear antibodies (ANAs) to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period. measured in UI/mL.
Measured: On day 10, day 30 and day 90 of follow-up period
To compare immune response markers: antiphospholipid antibodies (Abs) in patients with persistent COVID among the three treatment arms.
Change from baseline in antiphospholipid antibodies (Abs),) to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period. measured in UI/mL.
Measured: On day 10, day 30 and day 90 of follow-up period
To compare immune response markers: antimitochondrial antibodies in patients with persistent COVID among the three treatment arms.
Change from baseline in antimitochondrial antibodies to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period. measured in UI/mL.
Measured: On day 10, day 30 and day 90 of follow-up period
To compare the SARS-CoV-2 RNA antigenemia (presence of viral components) in plasma with persistent COVID among the three treatment arms.
Change from baseline in viral components (SARS-CoV-2 RNA antigenemia) in plasma to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period. The SARS-CoV-2 RNA is quantified in pg/mL.
Measured: On day 10, day 30 and day 90 of follow-up period
To compare alterations in Complement Activitation: Hemolytic Complement CH50 in patients with persistent COVID among the three treatment arms.
Change from baseline in Complement Activity: Hemolytic Complement CH50 to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period. measured in UI/mL.
Measured: On day 10, day 30 and day 90 of follow-up period
To compare alterations in thromboinflammatory components (prothrombin time (PT)), among the three treatment arms.
Change from baseline in prothrombin time (PT) ratio in plasma to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.
Measured: On day 10, day 30 and day 90 of follow-up period
To compare alterations in thromboinflammatory components (activated partial thromboplastin time (aPTT)), among the three treatment arms.
Change from baseline in activated partial thromboplastin time (aPTT) in seconds, in plasma to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.
Measured: On day 10, day 30 and day 90 of follow-up period
To compare alterations in thromboinflammatory components (D-Dimer), among the three treatment arms.
Change from baseline in D-Dimer measured in ng/mL, in plasma to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.
Measured: On day 10, day 30 and day 90 of follow-up period
To compare alterations in thromboinflammatory components (Fibrinogen), among the three treatment arms.
Change from baseline in Fibrinogen measured in mg/dL, in plasma to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.
Measured: On day 10, day 30 and day 90 of follow-up period
To compare alterations in thromboinflammatory components (Antithrombin III (ATIII)), among the three treatment arms.
Change from baseline in Antithrombin III (ATIII) measured in %, in plasma to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.
Measured: On day 10, day 30 and day 90 of follow-up period
To compare alterations in thromboinflammatory components (Factor de Von willebrand), among the three treatment arms.
Change from baseline in Factor de Von Willebrand measured in %, in plasma to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.
Measured: On day 10, day 30 and day 90 of follow-up period
To compare alterations in hormonal components (Serotonin) among the three treatment arms.
Change from baseline in serotonin (UI) in plasma to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period.
Measured: On day 10, day 30 and day 90 of follow-up period
To compare alterations in hormonal components (Dopamine) among the three treatment arms.
Change from baseline in dopamine alterations in plasma to day 10 (±2), day 30 (±2), and day 90 (±5) of the follow-up period. measured in ug/24 h
Measured: On day 10, day 30 and day 90 of follow-up period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2025
- Study start7 Feb 2025
- Primary completion29 Sep 2026
- Study completion29 Sep 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post COVID-19 ConditionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized (1:1:1), placebo-controlled, double-blind clinical trial
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
- Sponsor type
- University, hospital or other
- Collaborators
- PharmaMar, IrsiCaixa
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06766825
- Sponsor's protocol ID
- THALASSA 2.0
- Other IDs
- 2024-516378-31-00
- Acronym
- THALASSA
- Status last verified
- Oct 2026
- First submitted
- 31 Dec 2024
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT06766825
- Acronym / sponsor ID
- THALASSA / THALASSA 2.0
- Conditions
- Post COVID-19 Condition, Long COVID Syndrome, Persistent COVID-19, Persistent COVID Condition, Long COVID
- Keywords
- SARS-CoV-2, COVID-19, Long COVID19, Plitidepsin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la CienciaUniversity, hospital or other
- Collaborators
- PharmaMar, IrsiCaixa
- Study start
- 7 Feb 2025 (actual)
- Primary completion
- 29 Sep 2026 (actual)
- Study completion
- 29 Sep 2026 (actual)
- First posted
- 9 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Randomized (1:1:1), placebo-controlled, double-blind clinical trial
| Arm | Type | Receives |
|---|---|---|
| A. Plitidepsin Arm | Experimental | Drug: Plitidepsin 1.5 mg/daySubjects 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. |
| B. Placebo/Plitidepsin | Experimental | Drug: Placebo and Plitidepsin 1.5mg/daySubjects in arm B will receive 1h-IV placebo 1 vial /day during the first two treatment periods (Days 1 to 3 and Days 15 to 17) and plitidepsin 1.5 mg/day 1h-IV during the last two treatment periods (Days 29 to 31 and Days 43 to 45). |
| C. Placebo Arm | Placebo comparator | Drug: PlaceboSubjects in arm C will receive 1h-IV placebo 1 vial/day during the four treatment periods on Days 1 to 3, Days 15 to 17, Days 29 to 31, and Days 43 to 45. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (16 listed)
- Last SARS-CoV-2 vaccine dose during the previous 30 days.
- Patients with active uncontrolled infections.
- Patients infected by SARS-CoV-2 virus in the last 90 days prior to the screening visit.
- Patients receiving treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers (Annex 1) throughout plitidepsin treatment period and until 24-h washout period.
- Pacients receiving chronic glucocorticoid therapy (high-dose corticosteroids [ie, 20 mg of prednisone daily or equivalent for ≥2 weeks)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Plitidepsin 1.5 mg/dayReceive 1.5 mg/day of plitidepsin intravenously (IV) over a 1-hour infusion for 3 consecutive days every 15 days during 4 treatment periods. The participant will receive the following pre-medication before receiving the study treatment: * Palonosetron 0.25 mg IV * Dexchlorpheniramine maleate 5 mg IV (or equivalent to H1 receptor antihistamines) * Famotidine 40 mg oral (60 minutes before starting the plitidepsin/placebo infusion) * Dexamethasone phosphate 8 mg IV (equivalent to 6.6 mg of dexamethasone) Premedication should be completed 20-30 minutes before starting the plitidepsin/placebo infusion. | Drug | A. Plitidepsin Arm |
| PlaceboReceive placebo intravenously (IV) over a 1-hour infusion for 3 consecutive days every 15 days during 4 treatment periods. The participant will receive the following pre-medication before receiving the study treatment: * Palonosetron 0.25 mg IV * Dexchlorpheniramine maleate 5 mg IV (or equivalent to H1 receptor antihistamines) * Famotidine 40 mg oral (60 minutes before starting the plitidepsin/placebo infusion) * Dexamethasone phosphate 8 mg IV (equivalent to 6.6 mg of dexamethasone) Premedication should be completed 20-30 minutes before starting the plitidepsin/placebo infusion. | Drug | C. Placebo Arm |
| Placebo and Plitidepsin 1.5mg/dayReceive placebo intravenously (IV) over a 1-hour infusion for 3 consecutive days every 15 days during two treatment periods and receive plitidepsin 1.5mg/day during the last two treatment periods. The participant will receive the following pre-medication before receiving the study treatment: * Palonosetron 0.25 mg IV * Dexchlorpheniramine maleate 5 mg IV (or equivalent to H1 receptor antihistamines) * Famotidine 40 mg oral (60 minutes before starting the plitidepsin/placebo infusion) * Dexamethasone phosphate 8 mg IV (equivalent to 6.6 mg of dexamethasone) Premedication should be completed 20-30 minutes before starting the plitidepsin/placebo infusion. | Drug | B. Placebo/Plitidepsin |
Primary outcome
Change in the overall health in patients from each group using patient reported outcomes measurement information system score (PROMIS-29®).
Time frame: On day 90 of follow-up period
Difference between groups on the patient-reported outcomes measurement information system (PROMIS-29®) score health scale measured by T-Score; Each domain is scored on a 5-point scale, (without any difficulty, with a little difficulty, with some difficulty, with much difficulty, unable to do), in case of the pain domain is on a 10-point scale; from no pain to the worse pain. on day 90 (±5) of the follow-up period* (after the intervention).
28 secondary outcomes
To compare the safety/tolerability of Plitidepsin Vs placebo in terms of adverse events in patients with PCC.
Time frame: On day 90 of follow-up period
To compare the incidence of Treatment-Emergent Adverse Events (TEAEs) between groups.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare changes in the overall health in patients from each group using patient reported outcomes measurement information system score (PROMIS-29®).
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare functional capacity changes in patients from each group using the post-COVID-19 Functional State (PCFS) scale.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare symptomatic changes in patients from each group using the Can Ruti Questionnaire.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare changes in terms of Quality of Life (QoL) for each group.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare neuropsychological symptomatology [psychomotor speed and executive function] in patients with PCC among the three treatment arms.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare neuropsychological symptomatology [depressive symptoms] in patients with PCC among the three treatment arms.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare neuropsychological symptomatology [ anxiety symptoms] in patients with PCC among the three treatment arms.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare neuropsychological symptomatology [sleep quality] in patients with PCC among the three treatment arms.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare neuropsychological symptomatology [disability] in patients with PCC among the three treatment arms.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare changes in terms of physical activity in patients with PCC among the three arms.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare changes in terms of fatigue (Fatigue scale) in patients with PCC among the three treatment arms.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare changes in terms of fatigue (Five times sit to stant test) in patients with PCC among the three treatment arms.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare the evolution of inflammation markers in patients with PCC among the three arms.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare immune response markers: Antinuclear antibodies (ANAs) in patients with persistent COVID among the three treatment arms.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare immune response markers: antiphospholipid antibodies (Abs) in patients with persistent COVID among the three treatment arms.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare immune response markers: antimitochondrial antibodies in patients with persistent COVID among the three treatment arms.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare the SARS-CoV-2 RNA antigenemia (presence of viral components) in plasma with persistent COVID among the three treatment arms.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare alterations in Complement Activitation: Hemolytic Complement CH50 in patients with persistent COVID among the three treatment arms.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare alterations in thromboinflammatory components (prothrombin time (PT)), among the three treatment arms.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare alterations in thromboinflammatory components (activated partial thromboplastin time (aPTT)), among the three treatment arms.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare alterations in thromboinflammatory components (D-Dimer), among the three treatment arms.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare alterations in thromboinflammatory components (Fibrinogen), among the three treatment arms.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare alterations in thromboinflammatory components (Antithrombin III (ATIII)), among the three treatment arms.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare alterations in thromboinflammatory components (Factor de Von willebrand), among the three treatment arms.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare alterations in hormonal components (Serotonin) among the three treatment arms.
Time frame: On day 10, day 30 and day 90 of follow-up period
To compare alterations in hormonal components (Dopamine) among the three treatment arms.
Time frame: On day 10, day 30 and day 90 of follow-up period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2026.
- Individual participant dataSharing planned: No
Related trials for Post COVID-19 Condition
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Recruiting
Home-Based Exercise Tele-Rehabilitation After COVID-19
Post SARS-CoV2 (COVID-19)
Recruiting
Whole-body Cryotherapy in Those With Chronic Fatigue: A Feasibility Study
ME/CFS, Fibromyalgia (FM)
Not yet recruitingPhase 3
The Study of Brave-LC LDN Treatment Trial
Post-acute COVID-19 Syndrome
Active, not recruitingObservational study
Epigenetic Changes in Long COVID Patients
Long COVID-19 Syndrome, Long COVID Symptoms
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Plitidepsin 1.5 mg/day in people with Post COVID-19 Condition and Long COVID Syndrome, run by Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the overall health in patients from each group using patient reported outcomes measurement information system score (PROMIS-29®). (time frame: On day 90 of follow-up period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2026.