COVID-19 InfectionPhase 3NeptunoNCT04784559
Trial to Determine the Efficacy/Safety of Plitidepsin vs Control in Patients With Moderate COVID-19 Infection
A Phase 3 study testing Plitidepsin, Dexamethasone and Remdesivir in people with COVID-19 Infection, run by PharmaMar at 28 sites in 8 countries.
Trial summary
Treatment of patients hospitalised for management of moderate COVID-19 infection Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19 Infection
- What is being tested?
- Plitidepsin, Dexamethasone and Remdesivir
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 205 participants
- Where
- 28 sitesin 8 countries
- Study dates
- 4 Jun 2021to 1 Mar 2023
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Signed informed consent obtained prior to initiation of any study-specific procedures and study treatment.
- Documented diagnosis of SARS-CoV-2 infection, determined by either qualitative polymerase chain reaction (PCR), antigen test by local laboratory, or any other validated method approved by the local health authority, from appropriate biological samples collected no more than 72 hours prior to study treatment on Day 1.
- Patient meets category 5 on the 11-point WHO Clinical Progression Scale: requires hospitalisation and oxygen by mask or nasal prongs/cannula.
- A maximum of 14 days from onset of COVID-19 symptoms to initiation of study treatment on Day 1.
- Male or female aged ≥18 years.
- Adequate bone marrow, liver, kidney, and metabolic function, defined by the following tests performed at local laboratory:
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- Absolute neutrophil count ≥500/mm^3 (0.5 x 10^9/L).
- Platelet count ≥75,000/mm^3 (75 x 10^9/L).
- Alanine transaminase (ALT), aspartate transaminase (AST) ≤3 x upper limit of normal (ULN).
- Serum bilirubin ≤1 x ULN (or direct bilirubin <1 x ULN when total bilirubin is above ULN).
- Calculated creatinine clearance ≥30 mL/min (Cockcroft-Gault equation).
- Creatine phosphokinase (CPK) ≤2.5 x ULN except if the patient has had recent (i.e., in the last week) shivering episodes or trauma. In that case, the level of CPK should be ≤5 x ULN.
- Agree not to participate in another interventional clinical trial through Day 31.
- Females of reproductive capacity must have a negative serum or urine pregnancy test by local laboratory at study enrolment and must be non-lactating.
- Females and males with partners of child-bearing potential must use effective contraception while on study treatment and for 6 months after last dose of plitidepsin. Patients in the control arm must use effective contraception during the time indicated in the approved product information (summary of product characteristics [SmPC] or leaflet). If no information is available in the approved product information, patients in the control arm must use effective contraception for at least one week after the study completion or the time indicated based on the investigator's discretion.
Who cannot join
- Subjects with a pre-baseline (i.e., in the month preceding the current COVID-19 infection) impairment in general health condition for whatever reason except COVID-19, with a severe dependency for daily living activities (Barthel index ≤ 60/100) or chronic oxygen therapy.
- Having received treatment for COVID-19 in another clinical trial in the prior 4 weeks, except documented allocation in a placebo arm.
- Evidence of respiratory failure at the time of randomisation, based on resource utilisation requiring at least one of the following: endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula, non-invasive positive pressure ventilation, ECMO, or clinical diagnosis of respiratory failure (i.e., clinical need for one of the aforementioned therapies, which could not be administered in a resource-limited setting).
- Patients with severe COVID-19, meeting score >5 on the 11-point WHO Clinical Progression Scale or presenting, after an initial stabilisation prior to randomisation, any of clinical signs indicative of severe systemic illness, such as respiratory rate ≥30 per minute, heart rate ≥125 per minute, or PaO2/FiO2 <300. In case a direct measure of PaO2 has not been obtained, it should be imputed according to a referenced formula. For sites located over 1000 m above sea level, PaO2/FiO2 ratio will be adjusted.
- Patients receiving, at randomisation, treatment with antiviral therapy against SARS-CoV-2 or requiring anti-inflammatory/immunomodulating drugs beyond glucocorticoids with the exceptions listed below:
- Prior administration of dexamethasone or equivalent glucocorticoid might be acceptable if:
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- The total daily dose is not higher than 10 mg of dexamethasone phosphate (equivalent to dexamethasone base 8.25 mg/day) or equivalent glucocorticoids.
- The duration of the treatment does not exceed 72 hours prior to study treatment Day 1.
- Prior administration of dexamethasone or equivalent glucocorticoid might be acceptable if:
- The total daily dose is not higher than 10 mg of dexamethasone phosphate (equivalent to dexamethasone base 8.25 mg/day) or equivalent glucocorticoids.
- The duration of the treatment does not exceed 72 hours prior to study treatment Day 1.
- Prior administration of an antiviral might be acceptable in the following circumstances:
- For small molecules (e.g., remdesivir, molnupiravir, nirmaltrevir/ritonavir), they must have been given for an earlier stage of the disease, outside a clinical trial, and there should be a documentation of objective clinical deterioration plus evidence of persisting positivity for SARS-CoV-2 in appropriate biological samples. Last dose of previous antiviral drugs should have been administered at least 24 h before randomisation.
- For antiviral monoclonal antibodies, they must have been given for an earlier stage of the disease (including pre-exposure prophylaxis), outside a clinical trial, and there should be a documentation of objective clinical deterioration plus evidence of persisting positivity for SARS-CoV-2 in appropriate biological samples. Last dose of antiviral monoclonal antibodies should have been administered at least 1 week before randomisation.
- Patients receiving treatment with chloroquine or derivatives within 8 weeks before enrolment or during the study.
- Patients receiving treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers.
- Viral illness (other than COVID-19) requiring therapy, except for patients with treated and adequately controlled (undetectable) human immunodeficiency virus infection.
- Patients with uncontrolled known primary or secondary immunodeficiency, including chronic treatment with glucocorticoids (i.e., prednisone at a daily dose of >10 mg for >1 month, or another glucocorticoid at equipotent dose).
- Any of the following cardiac conditions or risk factors:
- Sinus bradycardia (<50 beats/min), sinus nodal dysfunction (sick sinus disease), atrioventricular block of any degree (PR >200 msec), or any other bradyarrhythmia (<50 beats/min), except for patients with permanent pacemakers;
- Cardiac infarction, cardiac surgery or cardiac insufficiency episode within the last 6 months;
- Known abnormal value of left ventricular ejection fraction (LVEF <low limit of normal (LLN)), unless documented confirmation of recovery (LVEF >LLN) in the previous month;
- QT interval corrected using Fridericia's formula (QTcF) >450 msec for males or >470 msec for females;
- History of known congenital or acquired QT prolongation;
- Uncorrected hypokalaemia, hypocalcaemia (adjusted) and/or hypomagnesemia at screening;
- Troponin test performed at local laboratory >1.5 x ULN; or
- Need for an unreplaceable drug that prolongs QT and it is clearly associated with a known risk for torsades de pointes (TdP); in case of being already on treatment with these aforementioned drugs, a minimum of 4 half-lives of the drug is required before replacement (if feasible).
- Hypersensitivity to the active ingredient or any of the excipients (mannitol, macrogolglycerol hydroxystearate, and ethanol) or patients for whom dexamethasone, antihistamine H1/H2 or antiserotoninergic agents are contraindicated.
- Females who are pregnant (negative serum or urine pregnancy test required for all females of child-bearing potential at screening) or breast feeding.
- Females and males with partners of child-bearing potential (females who are not surgically sterile or postmenopausal defined as amenorrhea for >12 months) who are not using at least 1 protocol specified method of contraception.
- Any other clinically significant medical condition (including major surgery within the last 3 weeks before screening) or laboratory abnormality that, in the opinion of the investigator, would jeopardise the safety of the patient or potentially impact on patient compliance or the safety/efficacy observations in the study.
Trial locations and contacts
28 sites in 8 countries.
28 sites in 8 countries
Spain17 sites
Hospital General Universitario de Alicante
Alicante, 3010
Hospital Universitari Germans Trias i Pujol
Badalona, Barcelona, 08916
Hospital Universitario HM Montepríncipe
Boadilla del Monte, Madrid, 28668
Hospital Universitario Virgen de las Nieves (HUVN)
Granada, 18014
Hospital Universitario de Guadalajara
Guadalajara, 19002
Hospital Universitario de Jerez de la Frontera
Jerez de la Frontera, Cádiz, 11407
Hospital Universitari de Bellvitge
L'Hospitalet de Llobregat, Barcelona, 08907
Hospital Infanta Leonor
Madrid, 28032
Hospital Universitario Ramón y Cajal
Madrid, 28034
Hospital Clínico San Carlos
Madrid, 28040
H. HM Sanchinarro
Madrid, 28050
Hospital de Emergencias Enfermera Isabel Zendal
Madrid, 28055
Hospital Quirónsalud Madrid
Pozuelo de Alarcón, Madrid, 28223
Hospital Universitario de Salamanca
Salamanca, 37007
Instituto de Investigación Sanitaria Valdecilla (IDIVAL)
Santander, 39008
Hospital Universitario Virgen del Rocío
Seville, 41013
Hospital Álvaro Cunqueiro
Vigo, Pontevedra, 36213
Romania4 sites
Institutul National De Boli Infectioase "Prof. Dr. Matei Bals"
Bucharest, 021105
Spitalul Clinic de Boli Infectioase si Tropicale Dr. Victor Babes - Bucharest
Bucharest, 030303
Spitalul Clinic De Boli Infectioase "Sfanta Parascheva" IASI, Sectia Boli Infectioase III
Iași, 700116
Spitalul Judetean de Urgenta 'Sf. Ioan cel Nou' Suceava, Sectia de Boli Infectioase
Suceava, 720237
Greece2 sites
Evangelismos Hospital General Hospital of Athens Evangelismos, Intensive Care Unit
Athens, 106 76
Sotiria Hospital General Hospital of Chest Diseases of Athens "Sotiria" 3rd Department of Internal Medicine of University of Athens
Athens, 115 27
France1 site
Centre Hospitalier Regional et Universitaire de Tours (CHRU Tours) - Hopital Bretonneau
Tours, 37044
Mexico1 site
Universidad Autonoma de Nuevo Leon - Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
Monterrey, Nuevo León, 64460
About this study
Official title: A Phase 3, Multicentre, Randomised, Controlled Trial to Determine the Efficacy and Safety of Two Dose Levels of Plitidepsin Versus Control in Adult Patient Requiring Hospitalisation for Management of Moderate COVID-19 Infection
Treatment of patients hospitalised for management of moderate COVID-19 infection
Read the detailed description
This is a multicentre, open-label, controlled Phase 3 study in which adults requiring hospital admission and O2 supplementation for management of moderate COVID-19 infection will be randomised in 1:1:1 to: Plitidepsin 1.5 mg arm, Plitidepsin 2.5 mg arm and Control arm
- Conditions
- COVID-19 Infection
- Being tested
- Plitidepsin, Dexamethasone, Remdesivir, Favipiravir
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlitidepsinDrug
Plitidepsin 2 mg powder is provided as a sterile, preservative-free, and white to off-white lyophilised powder/cake comprising 2 mg plitidepsin and mannitol in a single-dose, 10 mL clear type 1 glass vial.
Solvent for plitidepsin is provided as a sterile, preservative-free, clear, slightly viscous aqueous liquid (4 mL) containing macrogolglycerol ricinoleate and ethanol in a single-dose type 1 clear glass ampoule.
For administration, vial contents are reconstituted by addition of 4 mL of solvent for plitidepsin to obtain a slightly yellowish solution containing 0.5 mg/mL plitidepsin with mannitol, macrogolglycerol ricinoleate and ethanol excipients. The required amount of plitidepsin reconstituted solution is added to bag containing 0.9% sodium chloride or 5% glucose for IV injection and administered as an IV infusion over 60 minutes.
DexamethasoneDrug
Detailed information about the formulation, posology, packaging and labelling, storage, and manufacturer is provided in the current country-specific product information. The summary of product characteristics (SmPC) and/or leaflet provides detailed product information for investigators in the European Union and/or in other regions.
RemdesivirDrug
Detailed information about the formulation, posology, packaging and labelling, storage, and manufacturer is provided in the current country-specific product information. The summary of product characteristics (SmPC) and/or leaflet provides detailed product information for investigators in the European Union and/or in other regions.
FavipiravirDrug
Detailed information about the formulation, posology, packaging and labelling, storage, and manufacturer is provided in the current country-specific product information. The summary of product characteristics (SmPC) and/or leaflet provides detailed product information for investigators in the European Union and/or in other regions.
| Study group | Role | What they receive |
|---|---|---|
| Plitidepsin 1.5 mg arm | Experimental | Patients will receive plitidepsin 1.5 mg/day intravenous (IV) in addition to dexamethasone on days 1 to 3. Receives: Drug: Plitidepsin; Drug: Dexamethasone |
| Plitidepsin 2.5 mg arm | Experimental | Patients will receive plitidepsin 2.5 mg/day IV in addition to dexamethasone on days 1 to 3. Receives: Drug: Plitidepsin; Drug: Dexamethasone |
| Control arm | Active comparator | Patients will receive dexamethasone IV on Days 1 to 3. Additionally, in accordance with local treatment guidelines, patients in this group may receive a regulatory-approved antiviral treatment. Receives: Drug: Dexamethasone; Drug: Remdesivir; Drug: Favipiravir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to Sustained Withdrawal of Supplementary Oxygen With no Subsequent Reutilisation During Remaining Study Period
Time to sustained withdrawal of oxygen supplementation (in days) with no subsequent reutilisation during remaining study period is defined as the first day, from randomisation through completion of the study, on which a patient i. satisfies categories 0 to 4 on the 11-point WHO Clinical Progression Scale, and ii. has no subsequent reutilisation of oxygen supplementation (5 to 10 on the 11-point WHO Clinical Progression Scale).
The WHO clinical progression scale provides a measure of illness severity across a range from 0 (uninfected) to 10 (dead).
Measured: From administration date to Day 31(±3)
Secondary outcomes (6)
Time to Sustained (i.e., With no Subsequent Readmission to Day 31) Hospital Discharge (Since Randomisation).
Time to sustained (i.e., with no subsequent readmission to Day 31) hospital discharge (since randomization)
Measured: From administration date to Day 31(±3)
Clinical Status by the 11-category WHO Clinical Progression Scale on Day 8
The WHO clinical progression scale provides a measure of illness severity across a range from 0 (uninfected) to 10 (dead).
0 = Uninfected; no viral RNA detected
- = Ambulatory mild disease. Asymptomatic; viral RNA detected
- = Ambulatory mild disease. Symptomatic; independent
- = Ambulatory mild disease. Symptomatic; assistance needed
- = Hospitalized: moderate disease. Hospitalized; no oxygen therapy
- = Hospitalized: moderate disease. Hospitalized; oxygen by mask or nasal prongs
- = Hospitalized: severe diseases. Hospitalized; oxygen by NIV or high flow
- = Hospitalized: severe diseases. Intubation and mechanical ventilation pO2/FIO2 > 150 or SpO2/FIO2 > 200
- = Hospitalized: severe diseases. Mechanical ventilation pO2 /FIO2 <150 (SpO2 /FiO2 <200) or vasopressors
- = Hospitalized: severe diseases. Mechanical ventilation pO2 /FiO2 <150 and vasopressors, dialysis, or ECMO
- = dead
Measured: Day 8 (±1)
Total Duration of Advanced Oxygen Support
Total duration of advanced oxygen support (high-flow nasal oxygen, extracorporeal membrane oxygenation -ECMO-, non-invasive ventilation or mechanical ventilation).
Measured: From administration date to Day 31(±3)
Number of Participants in Each Study Group Requiring Admission to ICU
Number of participants in each study group requiring admission to intensive care unit
Measured: Day 4, Day 8(±1) , Day 15(±1) and Day 31(±3)
Frequency of Adverse Events
Adverse Event Types according to the National Cancer Institute [NCI]-Common Terminology Criteria for AEs (CTCAE v.5.0):
The number of participants who experienced treatment-emergent adverse events (TEAEs) are presented.
Measured: From administration date to Day 31(±3)
Frequency of TEAEs of ≥Grade 3 According to NCI-CTCAE for Adverse Events (Version 5.0), TEAEs of Special Interest, Serious TEAEs, Serious Treatment-related TEAEs, TEAEs Leading to Treatment Discontinuation, and Deaths
Frequency of treatment-emergent adverse events (TEAEs) of ≥grade 3 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 5.0), TEAEs of special interest, serious TEAEs, serious treatment-related TEAEs, TEAEs leading to treatment discontinuation, and deaths
Measured: From administration date to Day 31(±3)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2021
- Study start4 Jun 2021
- Primary completion1 Mar 2023
- Study completion1 Mar 2023
Why it stopped: Sponsor has decided to end the study prematurely based on significant difficulties in the recruitment of patients, despite the implementation of corrective measures that still failed to increase the accrual rate required for a feasible completion.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID-19 InfectionStudies 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients Will be randomised in 1:1:1 to: Plitidepsin 1.5 mg arm, Plitidepsin 2.5 mg arm and Control arm
- Masking
- None (open label)
- Enrolment
- 205 participants (actual)
Sponsor and investigators
- Lead sponsor
- PharmaMar
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- José Jimeno Doñaque, MD, PhD, Study director, PharmaMar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04784559
- Sponsor's protocol ID
- APL-D-003-20
- Other IDs
- 2020-005951-19
- Acronym
- Neptuno
- Status last verified
- Jan 2025
- First submitted
- 4 Mar 2021
- Last updated
- 21 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Landete P, Caliman-Sturdza OA, Lopez-Martin JA, Preotescu L, Luca MC, Kotanidou A, Villares P, Iglesias SP, Guisado-Vasco P, Saiz-Lou EM, Del Carmen Farinas-Alvarez M, de Lucas EM, Perez-Alba E, Cisneros JM, Estrada V, Hidalgo-Tenorio C, Poulakou G, Torralba M, Fortun J, Garcia-Ocana P, Lemaignen A, Marcos-Martin M, Molina M, Paredes R, Perez-Rodriguez MT, Raev D, Ryan P, Meira F, Gomez J, Torres N, Lopez-Mendoza D, Jimeno J, Varona JF. A Phase III Randomized Controlled Trial of Plitidepsin, a Marine-Derived Compound, in Hospitalized Adults With Moderate COVID-19. Clin Infect Dis. 2024 Oct 15;79(4):910-919. doi: 10.1093/cid/ciae227.
PubMed 39182994
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Multicentre, Randomised, Controlled Trial to Determine the Efficacy and Safety of Two Dose Levels of Plitidepsin Versus Control in Adult Patient Requiring Hospitalisation for Management of Moderate COVID-19 Infection
- ClinicalTrials.gov ID
- NCT04784559
- Acronym / sponsor ID
- Neptuno / APL-D-003-20
- Conditions
- COVID-19 Infection
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor has decided to end the study prematurely based on significant difficulties in the recruitment of patients, despite the implementation of corrective measures that still failed to increase the accrual rate required for a feasible completion.
- Enrolment
- 205 participants (actual)
- Lead sponsor
- PharmaMarIndustry (pharma, biotech, devices)
- Study start
- 4 Jun 2021 (actual)
- Primary completion
- 1 Mar 2023 (actual)
- Study completion
- 1 Mar 2023 (actual)
- First posted
- 5 Mar 2021 (actual)
- Results
- Posted 21 Feb 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Treatment of patients hospitalised for management of moderate COVID-19 infection
Detailed description
This is a multicentre, open-label, controlled Phase 3 study in which adults requiring hospital admission and O2 supplementation for management of moderate COVID-19 infection will be randomised in 1:1:1 to: Plitidepsin 1.5 mg arm, Plitidepsin 2.5 mg arm and Control arm
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Patients Will be randomised in 1:1:1 to: Plitidepsin 1.5 mg arm, Plitidepsin 2.5 mg arm and Control arm
| Arm | Type | Receives |
|---|---|---|
| Plitidepsin 1.5 mg arm | Experimental | Drug: Plitidepsin, Drug: DexamethasonePatients will receive plitidepsin 1.5 mg/day intravenous (IV) in addition to dexamethasone on days 1 to 3. |
| Plitidepsin 2.5 mg arm | Experimental | Drug: Plitidepsin, Drug: DexamethasonePatients will receive plitidepsin 2.5 mg/day IV in addition to dexamethasone on days 1 to 3. |
| Control arm | Active comparator | Drug: Dexamethasone, Drug: Remdesivir, Drug: FavipiravirPatients will receive dexamethasone IV on Days 1 to 3. Additionally, in accordance with local treatment guidelines, patients in this group may receive a regulatory-approved antiviral treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Signed informed consent obtained prior to initiation of any study-specific procedures and study treatment.
- Documented diagnosis of SARS-CoV-2 infection, determined by either qualitative polymerase chain reaction (PCR), antigen test by local laboratory, or any other validated method approved by the local health authority, from appropriate biological samples collected no more than 72 hours prior to study treatment on Day 1.
- Patient meets category 5 on the 11-point WHO Clinical Progression Scale: requires hospitalisation and oxygen by mask or nasal prongs/cannula.
- A maximum of 14 days from onset of COVID-19 symptoms to initiation of study treatment on Day 1.
- Male or female aged ≥18 years.
Key exclusion criteria (31 listed)
- Subjects with a pre-baseline (i.e., in the month preceding the current COVID-19 infection) impairment in general health condition for whatever reason except COVID-19, with a severe dependency for daily living activities (Barthel index ≤ 60/100) or chronic oxygen therapy.
- Having received treatment for COVID-19 in another clinical trial in the prior 4 weeks, except documented allocation in a placebo arm.
- Evidence of respiratory failure at the time of randomisation, based on resource utilisation requiring at least one of the following: endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula, non-invasive positive pressure ventilation, ECMO, or clinical diagnosis of respiratory failure (i.e., clinical need for one of the aforementioned therapies, which could not be administered in a resource-limited setting).
- Patients with severe COVID-19, meeting score >5 on the 11-point WHO Clinical Progression Scale or presenting, after an initial stabilisation prior to randomisation, any of clinical signs indicative of severe systemic illness, such as respiratory rate ≥30 per minute, heart rate ≥125 per minute, or PaO2/FiO2 <300. In case a direct measure of PaO2 has not been obtained, it should be imputed according to a referenced formula. For sites located over 1000 m above sea level, PaO2/FiO2 ratio will be adjusted.
- Patients receiving, at randomisation, treatment with antiviral therapy against SARS-CoV-2 or requiring anti-inflammatory/immunomodulating drugs beyond glucocorticoids with the exceptions listed below:
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 |
|---|---|---|
| PlitidepsinPlitidepsin 2 mg powder is provided as a sterile, preservative-free, and white to off-white lyophilised powder/cake comprising 2 mg plitidepsin and mannitol in a single-dose, 10 mL clear type 1 glass vial. Solvent for plitidepsin is provided as a sterile, preservative-free, clear, slightly viscous aqueous liquid (4 mL) containing macrogolglycerol ricinoleate and ethanol in a single-dose type 1 clear glass ampoule. For administration, vial contents are reconstituted by addition of 4 mL of solvent for plitidepsin to obtain a slightly yellowish solution containing 0.5 mg/mL plitidepsin with mannitol, macrogolglycerol ricinoleate and ethanol excipients. The required amount of plitidepsin reconstituted solution is added to bag containing 0.9% sodium chloride or 5% glucose for IV injection and administered as an IV infusion over 60 minutes. | Drug | Plitidepsin 1.5 mg arm, Plitidepsin 2.5 mg arm |
| DexamethasoneDetailed information about the formulation, posology, packaging and labelling, storage, and manufacturer is provided in the current country-specific product information. The summary of product characteristics (SmPC) and/or leaflet provides detailed product information for investigators in the European Union and/or in other regions. | Drug | Control arm, Plitidepsin 1.5 mg arm, Plitidepsin 2.5 mg arm |
| RemdesivirDetailed information about the formulation, posology, packaging and labelling, storage, and manufacturer is provided in the current country-specific product information. The summary of product characteristics (SmPC) and/or leaflet provides detailed product information for investigators in the European Union and/or in other regions. | Drug | Control arm |
| FavipiravirDetailed information about the formulation, posology, packaging and labelling, storage, and manufacturer is provided in the current country-specific product information. The summary of product characteristics (SmPC) and/or leaflet provides detailed product information for investigators in the European Union and/or in other regions. | Drug | Control arm |
Primary outcome
Time to Sustained Withdrawal of Supplementary Oxygen With no Subsequent Reutilisation During Remaining Study Period
Time frame: From administration date to Day 31(±3)
Time to sustained withdrawal of oxygen supplementation (in days) with no subsequent reutilisation during remaining study period is defined as the first day, from randomisation through completion of the study, on which a patient i. satisfies categories 0 to 4 on the 11-point WHO Clinical Progression Scale, and ii. has no subsequent reutilisation of oxygen supplementation (5 to 10 on the 11-point WHO Clinical Progression Scale). The WHO clinical progression scale provides a measure of illness severity across a range from 0 (uninfected) to 10 (dead).
6 secondary outcomes
Time to Sustained (i.e., With no Subsequent Readmission to Day 31) Hospital Discharge (Since Randomisation).
Time frame: From administration date to Day 31(±3)
Clinical Status by the 11-category WHO Clinical Progression Scale on Day 8
Time frame: Day 8 (±1)
Total Duration of Advanced Oxygen Support
Time frame: From administration date to Day 31(±3)
Number of Participants in Each Study Group Requiring Admission to ICU
Time frame: Day 4, Day 8(±1) , Day 15(±1) and Day 31(±3)
Frequency of Adverse Events
Time frame: From administration date to Day 31(±3)
Frequency of TEAEs of ≥Grade 3 According to NCI-CTCAE for Adverse Events (Version 5.0), TEAEs of Special Interest, Serious TEAEs, Serious Treatment-related TEAEs, TEAEs Leading to Treatment Discontinuation, and Deaths
Time frame: From administration date to Day 31(±3)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39182994Landete P, Caliman-Sturdza OA, Lopez-Martin JA, Preotescu L, Luca MC, Kotanidou A, Villares P, Iglesias SP, Guisado-Vasco P, Saiz-Lou EM, Del Carmen Farinas-Alvarez M, de Lucas EM, Perez-Alba E, Cisneros JM, Estrada V, Hidalgo-Tenorio C, Poulakou G, Torralba M, Fortun J, Garcia-Ocana P, Lemaignen A, Marcos-Martin M, Molina M, Paredes R, Perez-Rodriguez MT, Raev D, Ryan P, Meira F, Gomez J, Torres N, Lopez-Mendoza D, Jimeno J, Varona JF. A Phase III Randomized Controlled Trial of Plitidepsin, a Marine-Derived Compound, in Hospitalized Adults With Moderate COVID-19. Clin Infect Dis. 2024 Oct 15;79(4):910-919. doi: 10.1093/cid/ciae227.
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Post SARS-CoV2 (COVID-19)
Not yet recruitingPhase 1
A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine
COVID -19
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.
José Jimeno Doñaque, MD, PhD study director
PharmaMar
28 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Plitidepsin, Dexamethasone and Remdesivir in people with COVID-19 Infection, run by PharmaMar at 28 sites in 8 countries.
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 15 inclusion and 31 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: stopped early, as of the sponsor's last update on 21 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 28 sites in Spain, Romania, Greece, Brazil, Bulgaria and 3 more countries. 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Time to Sustained Withdrawal of Supplementary Oxygen With no Subsequent Reutilisation During Remaining Study Period (time frame: From administration date to Day 31(±3)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04784559, which also lists 1 linked publication.
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 21 Feb 2025.