COVID-19
Conditions
Keywords
COVID-19, Plitidepsin
Brief summary
The primary objective of this study is to evaluate efficacy of plitidepsin in pre-specified groups of immunocompromised patients with symptomatic COVID-19 requiring hospital care versus control in terms of mortality.
Interventions
DRUGPlitidepsin
IV infusion over 60-minutes
Sponsors
PharmaMar
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Signed informed consent obtained prior to initiation of any study-specific procedures and study treatment. * Participant aged ≥18 years. * Participant diagnosed COVID-19, with the following characteristics: 1. A regulatory-approved test, collected no more than 3 days prior to study randomisation, with either a Ct value ≤30 or a positive antigen test. 2. Presence of any of the selected signs/symptom listed in the COVID-19 signs/symptoms checklist within the last 24 hours. * Participant already admitted or requiring hospital care for symptomatic COVID-19, for which at least one antiviral has failed or cannot be used (i.e., contraindication, absence of labelled indication, guidelines or drug unavailability), after a minimum washout period of 24 hours for small molecules (e.g., remdesivir, molnupiravir, nirmaltrevir, ritonavir) and 5 days for antiviral monoclonal antibodies (e.g., tixagevimab + cilgavimab) or convalescent plasma. * Adequate bone marrow, liver, kidney, and metabolic function, defined by the following tests performed at local laboratory: 1. Absolute neutrophil count ≥500/mm\^3 (0.5 x 109/L). 2. Platelet count ≥ 50 000/mm3 (50 x 109/L). 3. Alanine transaminase (ALT) ≤3 x upper limit of normal (ULN) (≤5 x ULN if preexistent liver involvement by the underlying disease). 4. Serum bilirubin ≤1.5 x ULN (or direct bilirubin \<1.5 x ULN when total bilirubin is above ULN). 5. Estimated glomerular filtration rate ≥30 mL/min (CKD-EPI Creatinine Equation \[2021\]). * Females of child-bearing potential must have a negative serum or urine pregnancy test by local laboratory at screening and must be non-lactating. * Females of child-bearing potential and fertile males with partners of child-bearing potential must use contraceptive methods as specified in the protocol. Group-specific inclusion criteria: * Group 1 - Patients receiving, within the last 30 days, immune-suppressive therapy due to haematopoietic or organ transplantation. * Group 2 - Participants receiving B-cell depleting therapies within the last 6 months (with the exception of CAR-T cell therapy for which time restriction is not applicable). * Group 3 - Participants receiving, within the last 30 days, other immune-suppressive therapies. * Group 4 - Other situations with immunodeficiency. 1. Primary immune deficiencies. 2. Human immunodeficiency virus (HIV) infection, with CD4\^+ T lymphocyte \< 200 cells/μL in the last month. 3. Radiation therapy within the last 3 months- requires documentation of ALC \< 500 cells/μL. 4. Haematological neoplasia or myelodysplasia not currently receiving any therapy. 5. Other situations with a documentation of ALC \< 500 cells/μL.
Exclusion criteria
* Evidence of critical illness. * Any of the following cardiac conditions or risk factors: 1. Cardiac infarction or cardiac surgery episode within the last month. 2. History of known congenital QT prolongation. 3. Known structural cardiomyopathy with abnormal left ventricular ejection fraction (LVEF) (\<50%). 4. 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 dexamethasone, antihistamine H1/H2, or anti-serotoninergic 5HT3 agents. * Females who are pregnant or breast-feeding. * Females and males with partners of child-bearing potential who are not using at least 1 protocol-specified method of contraception. * Any situation currently requiring increasing needs of immune-suppressive agents. * Any other clinically significant medical condition or laboratory abnormality that, in the opinion of the investigator, would jeopardise the safety of the participant or potentially impact on participant compliance or the safety/efficacy observations in the study. * Participation in another clinical study involving an investigational drug within 30 days prior to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| One-month All-cause Mortality Rate | Day 1 to Day 30 (±2) | In the event of the participant initiating another non-protocol therapy, 1-month all-cause mortality rate was evaluated regardless of initiation of new non-protocol therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Sustained End of COVID-related Hospital Care | Day 1 to Day 60 (±3) | Time to sustained end of COVID-related hospital care from the time of randomisation was calculated as time from randomisation to the corresponding event using KM estimates. Participants with no available data for any time to event efficacy endpoint were censored at time 0, end of study (Day 60 ±3), or date of early study termination. Also, participants who had not achieved the time to event endpoint were censored at the last valid assessment. |
| Time to Sustained Improvement and Resolution of Selected COVID-19 Signs/Symptoms | Day 1 to Day 60 (±3) | Time to sustained improvement and resolution of all targeted COVID-19 signs/symptoms was calculated as time from randomisation to the corresponding event using KM estimates. Corresponding events were defined as the event occurring on the first of 4 consecutive days when all symptoms scored as National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v5.0; category of moderate-severe intensity, or requiring medical intervention, or limiting instrumental activity of daily living are scored as mild or absent AND all symptoms scored mild or 0 (absent) at study entry are scored as 0. Participants with no available data for any time to event efficacy endpoint were censored at time 0, end of study (Day 60 ±3), or date of early study termination. Also, participants who had not achieved the time to event endpoint were censored at the last valid assessment. |
| Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Days 4 (±1), 8 (±1), 15 (±1), 30 (±2), and 60 (±3) | Distribution of participants according to their clinical status by the 11-category WHO CPS: * Uninfected; no viral ribonucleic acid (RNA) detected * Asymptomatic; viral RNA detected * Symptomatic; independent * Symptomatic; assistance needed * Hospitalised; no oxygen therapy * Hospitalised; oxygen by mask or nasal prongs * Hospitalised; oxygen by non-invasive ventilation (NIV) or high flow * Intubation and mechanical ventilation * Mechanical ventilation or vasopressors * Mechanical ventilation and vasopressors, dialysis, or extracorporeal membrane oxygenation (ECMO) OR * Death. |
| Time to Confirmed Negativisation in SARS-CoV-2 Antigen Test or Real Time Polymerase Chain Reaction (RT-PCR) Cycle Threshold (Ct) > 30 | Day 1 to Day 60 (±3) | Time to confirmed negativisation in SARS-CoV antigen test or RT-PCR Ct\>30 was calculated as time from randomisation to the corresponding event using Kaplan-Meier (KM) estimates. Participants with no available data for any time to event efficacy endpoint were censored at time 0, end of study (Day 60 ±3), or date of early study termination. Also, participants who had not achieved the time to event endpoint were censored at the last valid assessment. |
| Time to Sustained Discontinuation of Oxygen Supplementation | Day 1 to Day 60 (±3) | Time to sustained discontinuation is calculated as time from randomisation to the corresponding event using KM estimates. Corresponding events were defined as discontinuation of oxygen supplementation for at least 7 days. Participants with no available data for any time to event efficacy endpoint were censored at time 0, end of study (Day 60 ±3), or date of early study termination. Also, participants who had not achieved the time to event endpoint were censored at the last valid assessment. |
| Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Day 1 to Day 60 (±3) | Frequency of the following events (all-cause and treatment-related) are included: * TEAEs * TEAEs ≥ grade 3 according to the NCI CTCAE v5.0 * TEAEs of special interest * Serious TEAEs * Serious adverse reactions (SARs) * AEs leading to treatment discontinuation * Deaths (related to COVID-19/all) Clinically relevant/significant changes from Baseline in laboratory parameters and vital signs were reported as AEs. |
| Number of Participants Requiring Oxygen Therapy | Days 4 (±1), 8 (±1), 15 (±1), 30 (±2), and 60 (±3) | The maximum number of participants requiring oxygen therapy on any day during each visit window is reported. |
Countries
Belgium, France, Georgia, Greece, Hungary, Israel, Italy, Poland, Portugal, Spain, United Kingdom
Participant flow
Recruitment details
A total of 37 participants were enrolled at 15 investigative sites between April 2023 and April 2024. Randomised participants who received at least 1 dose of study treatment and completed follow-up for survival until Day 30 (±2) were included in the Full Analysis Set (FAS) population.
Participants by arm
| Arm | Count |
|---|---|
| Group 1: Plitidepsin 2.5 mg Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 1.
Group 1 - Participants who received immune-suppression due to haematopoietic or organ transplantation. | 2 |
| Group 1: Control Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) ± other regulatory-approved antiviral (if clinically indicated) were administered to participants in Group 1.
Group 1 - Participants who received immune-suppression due to haematopoietic or organ transplantation. | 1 |
| Group 2: Plitidepsin 2.5 mg Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 2.
Group 2 - Participants who received B-cell depleting therapies. | 10 |
| Group 2: Control Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) ± other regulatory-approved antiviral (if clinically indicated) were administered to participants in Group 2.
Group 2 - Participants who received B-cell depleting therapies. | 3 |
| Group 3: Plitidepsin 2.5 mg Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 3.
Group 3 - Participants who received other immune-suppressive therapies. | 1 |
| Group 3: Control Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) ± other regulatory-approved antiviral (if clinically indicated) were administered to participants in Group 3.
Group 3 - Participants who received other immune-suppressive therapies. | 1 |
| Group 4: Plitidepsin 2.5 mg Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute IV infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) were administered to participants in Group 4.
Group 4 - Other situations with immune deficiencies. | 7 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 0 | 0 | 3 | 0 | 1 | 1 | 1 |
| Overall Study | Discontinued Prior to FAS Eligibility | 0 | 0 | 1 | 1 | 0 | 0 | 1 |
| Overall Study | Randomised but not Treated | 0 | 2 | 0 | 7 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Group 1: Plitidepsin 2.5 mg | Group 1: Control | Group 2: Plitidepsin 2.5 mg | Group 2: Control | Group 3: Plitidepsin 2.5 mg | Group 3: Control | Group 4: Plitidepsin 2.5 mg | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Customized < 65 years | 1 Participants | 0 Participants | 3 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 6 Participants |
| Age, Customized ≥ 65 years - < 75 years | 1 Participants | 1 Participants | 6 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 12 Participants |
| Age, Customized ≥ 75 years | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 5 Participants | 7 Participants |
| Ethnicity Not Collected | — | — | — | — | — | — | — | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 1 Participants | 10 Participants | 3 Participants | 1 Participants | 1 Participants | 5 Participants | 23 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 5 Participants | 2 Participants | 0 Participants | 0 Participants | 5 Participants | 14 Participants |
| Sex: Female, Male Male | 1 Participants | 0 Participants | 5 Participants | 1 Participants | 1 Participants | 1 Participants | 2 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 2 | 0 / 1 | 3 / 11 | 0 / 4 | 1 / 1 | 1 / 1 | 1 / 8 |
| other Total, other adverse events | 1 / 2 | 1 / 1 | 10 / 11 | 4 / 4 | 1 / 1 | 1 / 1 | 6 / 8 |
| serious Total, serious adverse events | 1 / 2 | 0 / 1 | 5 / 11 | 4 / 4 | 1 / 1 | 1 / 1 | 2 / 8 |
Outcome results
Primary
One-month All-cause Mortality Rate
In the event of the participant initiating another non-protocol therapy, 1-month all-cause mortality rate was evaluated regardless of initiation of new non-protocol therapy.
Time frame: Day 1 to Day 30 (±2)
Population: FAS Population: All randomised participants who received at least 1 dose of study treatment (plitidepsin or control) and completed follow-up for survival until Day 30 (±2). Participants who died before the end of the follow-up period were also included in the FAS population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1: Plitidepsin 2.5 mg | One-month All-cause Mortality Rate | 0.0 percentage of participants |
| Group 1: Control | One-month All-cause Mortality Rate | 0.0 percentage of participants |
| Group 2: Plitidepsin 2.5 mg | One-month All-cause Mortality Rate | 20.0 percentage of participants |
| Group 2: Control | One-month All-cause Mortality Rate | 0.0 percentage of participants |
| Group 3: Plitidepsin 2.5 mg | One-month All-cause Mortality Rate | 0.0 percentage of participants |
| Group 3: Control | One-month All-cause Mortality Rate | 100.0 percentage of participants |
| Group 4: Plitidepsin 2.5 mg | One-month All-cause Mortality Rate | 14.3 percentage of participants |
Secondary
Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS)
Distribution of participants according to their clinical status by the 11-category WHO CPS: * Uninfected; no viral ribonucleic acid (RNA) detected * Asymptomatic; viral RNA detected * Symptomatic; independent * Symptomatic; assistance needed * Hospitalised; no oxygen therapy * Hospitalised; oxygen by mask or nasal prongs * Hospitalised; oxygen by non-invasive ventilation (NIV) or high flow * Intubation and mechanical ventilation * Mechanical ventilation or vasopressors * Mechanical ventilation and vasopressors, dialysis, or extracorporeal membrane oxygenation (ECMO) OR * Death.
Time frame: Days 4 (±1), 8 (±1), 15 (±1), 30 (±2), and 60 (±3)
Population: FAS Population: All randomised participants who received at least 1 dose of study treatment (plitidepsin or control) and completed follow-up for survival until Day 30 (±2). Participants who died before the end of the follow-up period were also included in the FAS population. Number of participants analysed represents participants with available data at each individual timepoint.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Symptomatic; assistance needed | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Asymptomatic; viral RNA detected | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Hospitalised; oxygen by mask or nasal prongs | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Intubation and mechanical ventilation | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Hospitalised; no oxygen therapy | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Symptomatic; independent | 1 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Symptomatic; independent | 1 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Hospitalised; no oxygen therapy | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Symptomatic; independent | 2 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Hospitalised; oxygen by mask or nasal prongs | 1 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Intubation and mechanical ventilation | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Symptomatic; assistance needed | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Asymptomatic; viral RNA detected | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Symptomatic; assistance needed | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Intubation and mechanical ventilation | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Uninfected; no viral RNA detected | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Dead | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Symptomatic; independent | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Dead | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Hospitalised; oxygen by mask or nasal prongs | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Uninfected; no viral RNA detected | 1 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Asymptomatic; viral RNA detected | 1 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Asymptomatic; viral RNA detected | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Dead | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Hospitalised; no oxygen therapy | 1 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Uninfected; no viral RNA detected | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Uninfected; no viral RNA detected | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Hospitalised; oxygen by mask or nasal prongs | 1 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Dead | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Intubation and mechanical ventilation | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Asymptomatic; viral RNA detected | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Intubation and mechanical ventilation | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Symptomatic; assistance needed | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Hospitalised; no oxygen therapy | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Hospitalised; no oxygen therapy | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Symptomatic; independent | 1 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Dead | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Uninfected; no viral RNA detected | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Hospitalised; oxygen by mask or nasal prongs | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Symptomatic; assistance needed | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Uninfected; no viral RNA detected | 1 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Dead | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Intubation and mechanical ventilation | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Asymptomatic; viral RNA detected | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Symptomatic; independent | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Hospitalised; oxygen by mask or nasal prongs | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Symptomatic; assistance needed | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Hospitalised; no oxygen therapy | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Dead | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Uninfected; no viral RNA detected | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Asymptomatic; viral RNA detected | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Symptomatic; independent | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Dead | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Hospitalised; oxygen by mask or nasal prongs | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Symptomatic; assistance needed | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Hospitalised; no oxygen therapy | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Hospitalised; no oxygen therapy | 1 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Symptomatic; assistance needed | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Hospitalised; oxygen by mask or nasal prongs | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Symptomatic; independent | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Intubation and mechanical ventilation | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Asymptomatic; viral RNA detected | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Uninfected; no viral RNA detected | 1 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Dead | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Intubation and mechanical ventilation | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Uninfected; no viral RNA detected | 1 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Asymptomatic; viral RNA detected | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Symptomatic; independent | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Hospitalised; oxygen by mask or nasal prongs | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Hospitalised; no oxygen therapy | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Hospitalised; no oxygen therapy | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Symptomatic; assistance needed | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Hospitalised; oxygen by mask or nasal prongs | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Symptomatic; independent | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Intubation and mechanical ventilation | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Symptomatic; assistance needed | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Asymptomatic; viral RNA detected | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Uninfected; no viral RNA detected | 1 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Dead | 0 Participants |
| Group 1: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Intubation and mechanical ventilation | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Hospitalised; no oxygen therapy | 4 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Mechanical ventilation or vasopressors | 1 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Symptomatic; independent | 4 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Dead | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Symptomatic; assistance needed | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Hospitalised; no oxygen therapy | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Hospitalised; no oxygen therapy | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Symptomatic; assistance needed | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Symptomatic; assistance needed | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Symptomatic; independent | 1 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Hospitalised; oxygen by mask or nasal prongs | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Uninfected; no viral RNA detected | 3 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Hospitalised; no oxygen therapy | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Symptomatic; assistance needed | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Mechanical ventilation or vasopressors | 2 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Asymptomatic; viral RNA detected | 2 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Uninfected; no viral RNA detected | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Asymptomatic; viral RNA detected | 2 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Hospitalised; oxygen by mask or nasal prongs | 1 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Mechanical ventilation or vasopressors | 1 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Symptomatic; independent | 1 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Dead | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Symptomatic; assistance needed | 1 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Intubation and mechanical ventilation | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Hospitalised; oxygen by NIV or high flow | 1 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Dead | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Hospitalised; no oxygen therapy | 1 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Uninfected; no viral RNA detected | 3 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Hospitalised; oxygen by mask or nasal prongs | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Intubation and mechanical ventilation | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Asymptomatic; viral RNA detected | 2 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Intubation and mechanical ventilation | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Intubation and mechanical ventilation | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Dead | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Dead | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Intubation and mechanical ventilation | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Asymptomatic; viral RNA detected | 2 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 1 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Uninfected; no viral RNA detected | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Hospitalised; oxygen by NIV or high flow | 2 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Symptomatic; independent | 1 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Symptomatic; independent | 1 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Asymptomatic; viral RNA detected | 3 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Uninfected; no viral RNA detected | 2 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Hospitalised; oxygen by mask or nasal prongs | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Hospitalised; oxygen by mask or nasal prongs | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Dead | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Asymptomatic; viral RNA detected | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Hospitalised; no oxygen therapy | 2 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Hospitalised; no oxygen therapy | 1 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Hospitalised; no oxygen therapy | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Asymptomatic; viral RNA detected | 1 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Intubation and mechanical ventilation | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Uninfected; no viral RNA detected | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Asymptomatic; viral RNA detected | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Symptomatic; independent | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Symptomatic; assistance needed | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Hospitalised; no oxygen therapy | 2 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Hospitalised; oxygen by mask or nasal prongs | 1 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Intubation and mechanical ventilation | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Dead | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Uninfected; no viral RNA detected | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Symptomatic; independent | 1 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Symptomatic; assistance needed | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Hospitalised; oxygen by mask or nasal prongs | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Intubation and mechanical ventilation | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Dead | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Uninfected; no viral RNA detected | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Asymptomatic; viral RNA detected | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Symptomatic; independent | 1 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Symptomatic; assistance needed | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Hospitalised; oxygen by mask or nasal prongs | 1 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Intubation and mechanical ventilation | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Dead | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Uninfected; no viral RNA detected | 1 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Asymptomatic; viral RNA detected | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Dead | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Symptomatic; independent | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Symptomatic; assistance needed | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Hospitalised; oxygen by mask or nasal prongs | 2 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Uninfected; no viral RNA detected | 1 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Symptomatic; independent | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Symptomatic; assistance needed | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Hospitalised; no oxygen therapy | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Hospitalised; oxygen by mask or nasal prongs | 1 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Intubation and mechanical ventilation | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 2: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Uninfected; no viral RNA detected | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Intubation and mechanical ventilation | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Dead | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Intubation and mechanical ventilation | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Dead | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Uninfected; no viral RNA detected | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Intubation and mechanical ventilation | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Symptomatic; assistance needed | 1 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Asymptomatic; viral RNA detected | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Hospitalised; oxygen by NIV or high flow | 1 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Hospitalised; oxygen by mask or nasal prongs | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Uninfected; no viral RNA detected | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Symptomatic; independent | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Hospitalised; no oxygen therapy | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Symptomatic; assistance needed | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Hospitalised; no oxygen therapy | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Symptomatic; independent | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Hospitalised; oxygen by mask or nasal prongs | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Asymptomatic; viral RNA detected | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Dead | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Dead | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Uninfected; no viral RNA detected | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Intubation and mechanical ventilation | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Asymptomatic; viral RNA detected | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Hospitalised; oxygen by NIV or high flow | 1 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Symptomatic; independent | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Hospitalised; oxygen by mask or nasal prongs | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Asymptomatic; viral RNA detected | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Symptomatic; assistance needed | 1 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Hospitalised; no oxygen therapy | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Symptomatic; assistance needed | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Hospitalised; no oxygen therapy | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Symptomatic; independent | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Hospitalised; oxygen by mask or nasal prongs | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Uninfected; no viral RNA detected | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Symptomatic; assistance needed | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Hospitalised; no oxygen therapy | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Symptomatic; independent | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Intubation and mechanical ventilation | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Hospitalised; oxygen by mask or nasal prongs | 1 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Asymptomatic; viral RNA detected | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Dead | 0 Participants |
| Group 3: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Uninfected; no viral RNA detected | 1 Participants |
| Group 3: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 3: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Symptomatic; assistance needed | 0 Participants |
| Group 3: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 3: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Asymptomatic; viral RNA detected | 0 Participants |
| Group 3: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 3: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Dead | 0 Participants |
| Group 3: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Asymptomatic; viral RNA detected | 0 Participants |
| Group 3: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Hospitalised; oxygen by mask or nasal prongs | 0 Participants |
| Group 3: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Hospitalised; no oxygen therapy | 0 Participants |
| Group 3: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 3: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 3: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Hospitalised; no oxygen therapy | 0 Participants |
| Group 3: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Dead | 0 Participants |
| Group 3: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Symptomatic; independent | 0 Participants |
| Group 3: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Hospitalised; oxygen by mask or nasal prongs | 0 Participants |
| Group 3: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Intubation and mechanical ventilation | 0 Participants |
| Group 3: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Symptomatic; assistance needed | 0 Participants |
| Group 3: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 3: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Intubation and mechanical ventilation | 0 Participants |
| Group 3: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Uninfected; no viral RNA detected | 1 Participants |
| Group 3: Control | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Symptomatic; independent | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Dead | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Hospitalised; oxygen by NIV or high flow | 1 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Symptomatic; assistance needed | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Hospitalised; oxygen by mask or nasal prongs | 1 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Dead | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Hospitalised; oxygen by NIV or high flow | 2 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Intubation and mechanical ventilation | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Dead | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Symptomatic; independent | 1 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Hospitalised; oxygen by mask or nasal prongs | 1 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Uninfected; no viral RNA detected | 2 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Intubation and mechanical ventilation | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Hospitalised; no oxygen therapy | 5 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Asymptomatic; viral RNA detected | 2 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Symptomatic; independent | 1 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Asymptomatic; viral RNA detected | 2 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Symptomatic; assistance needed | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Hospitalised; oxygen by mask or nasal prongs | 1 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Symptomatic; assistance needed | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Symptomatic; independent | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Hospitalised; no oxygen therapy | 1 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Hospitalised; no oxygen therapy | 1 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Symptomatic; assistance needed | 1 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Symptomatic; assistance needed | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Hospitalised; no oxygen therapy | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Symptomatic; independent | 1 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Symptomatic; independent | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Hospitalised; no oxygen therapy | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Asymptomatic; viral RNA detected | 2 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Asymptomatic; viral RNA detected | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Hospitalised; oxygen by mask or nasal prongs | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 8 | Uninfected; no viral RNA detected | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Dead | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Hospitalised; oxygen by mask or nasal prongs | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Uninfected; no viral RNA detected | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Dead | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Mechanical ventilation and vasopressors, dialysis, or ECMO | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Uninfected; no viral RNA detected | 1 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Intubation and mechanical ventilation | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Uninfected; no viral RNA detected | 4 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 4 | Intubation and mechanical ventilation | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Intubation and mechanical ventilation | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 30 | Mechanical ventilation or vasopressors | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Hospitalised; oxygen by NIV or high flow | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 60 | Asymptomatic; viral RNA detected | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS) | Day 15 | Mechanical ventilation or vasopressors | 0 Participants |
Secondary
Number of Participants Requiring Oxygen Therapy
The maximum number of participants requiring oxygen therapy on any day during each visit window is reported.
Time frame: Days 4 (±1), 8 (±1), 15 (±1), 30 (±2), and 60 (±3)
Population: FAS Population: All randomised participants who received at least 1 dose of study treatment (plitidepsin or control) and completed follow-up for survival until Day 30 (±2). Participants who died before the end of the follow-up period were also included in the FAS population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: Plitidepsin 2.5 mg | Number of Participants Requiring Oxygen Therapy | Day 8 | 1 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants Requiring Oxygen Therapy | Day 4 | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants Requiring Oxygen Therapy | Day 15 | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants Requiring Oxygen Therapy | Day 60 | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants Requiring Oxygen Therapy | Day 30 | 0 Participants |
| Group 1: Control | Number of Participants Requiring Oxygen Therapy | Day 15 | 0 Participants |
| Group 1: Control | Number of Participants Requiring Oxygen Therapy | Day 30 | 0 Participants |
| Group 1: Control | Number of Participants Requiring Oxygen Therapy | Day 8 | 0 Participants |
| Group 1: Control | Number of Participants Requiring Oxygen Therapy | Day 4 | 0 Participants |
| Group 1: Control | Number of Participants Requiring Oxygen Therapy | Day 60 | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants Requiring Oxygen Therapy | Day 15 | 3 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants Requiring Oxygen Therapy | Day 4 | 2 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants Requiring Oxygen Therapy | Day 8 | 3 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants Requiring Oxygen Therapy | Day 30 | 1 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants Requiring Oxygen Therapy | Day 60 | 1 Participants |
| Group 2: Control | Number of Participants Requiring Oxygen Therapy | Day 8 | 1 Participants |
| Group 2: Control | Number of Participants Requiring Oxygen Therapy | Day 60 | 1 Participants |
| Group 2: Control | Number of Participants Requiring Oxygen Therapy | Day 4 | 1 Participants |
| Group 2: Control | Number of Participants Requiring Oxygen Therapy | Day 15 | 1 Participants |
| Group 2: Control | Number of Participants Requiring Oxygen Therapy | Day 30 | 1 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants Requiring Oxygen Therapy | Day 60 | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants Requiring Oxygen Therapy | Day 30 | 1 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants Requiring Oxygen Therapy | Day 8 | 1 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants Requiring Oxygen Therapy | Day 4 | 1 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants Requiring Oxygen Therapy | Day 15 | 1 Participants |
| Group 3: Control | Number of Participants Requiring Oxygen Therapy | Day 8 | 0 Participants |
| Group 3: Control | Number of Participants Requiring Oxygen Therapy | Day 15 | 1 Participants |
| Group 3: Control | Number of Participants Requiring Oxygen Therapy | Day 4 | 0 Participants |
| Group 3: Control | Number of Participants Requiring Oxygen Therapy | Day 60 | 0 Participants |
| Group 3: Control | Number of Participants Requiring Oxygen Therapy | Day 30 | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants Requiring Oxygen Therapy | Day 60 | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants Requiring Oxygen Therapy | Day 30 | 1 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants Requiring Oxygen Therapy | Day 15 | 1 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants Requiring Oxygen Therapy | Day 4 | 3 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants Requiring Oxygen Therapy | Day 8 | 3 Participants |
Secondary
Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)
Frequency of the following events (all-cause and treatment-related) are included: * TEAEs * TEAEs ≥ grade 3 according to the NCI CTCAE v5.0 * TEAEs of special interest * Serious TEAEs * Serious adverse reactions (SARs) * AEs leading to treatment discontinuation * Deaths (related to COVID-19/all) Clinically relevant/significant changes from Baseline in laboratory parameters and vital signs were reported as AEs.
Time frame: Day 1 to Day 60 (±3)
Population: As Treated Population: All participants who received any exposure to study treatment (plitidepsin or control). As Treated population was analysed according to the treatment they actually received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE of special interest | 1 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related serious TEAE | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any serious TEAE | 1 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE leading to death | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE | 1 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE | 1 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE ≥ grade 3 | 1 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE leading to death | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE ≥ grade 3 | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE leading to treatment discontinuation | 0 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE of special interest | 1 Participants |
| Group 1: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE leading to treatment discontinuation | 0 Participants |
| Group 1: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE ≥ grade 3 | 0 Participants |
| Group 1: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE leading to death | 0 Participants |
| Group 1: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE leading to death | 0 Participants |
| Group 1: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE leading to treatment discontinuation | 0 Participants |
| Group 1: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE of special interest | 0 Participants |
| Group 1: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any serious TEAE | 0 Participants |
| Group 1: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE ≥ grade 3 | 0 Participants |
| Group 1: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE leading to treatment discontinuation | 0 Participants |
| Group 1: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related serious TEAE | 0 Participants |
| Group 1: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE | 0 Participants |
| Group 1: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE of special interest | 0 Participants |
| Group 1: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE | 1 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE | 10 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE of special interest | 4 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE ≥ grade 3 | 5 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE | 4 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE leading to treatment discontinuation | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE ≥ grade 3 | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE leading to death | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE of special interest | 1 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related serious TEAE | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any serious TEAE | 5 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE leading to treatment discontinuation | 0 Participants |
| Group 2: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE leading to death | 3 Participants |
| Group 2: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE leading to death | 0 Participants |
| Group 2: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE | 4 Participants |
| Group 2: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE | 1 Participants |
| Group 2: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE ≥ grade 3 | 4 Participants |
| Group 2: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE ≥ grade 3 | 0 Participants |
| Group 2: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE of special interest | 2 Participants |
| Group 2: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE of special interest | 1 Participants |
| Group 2: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any serious TEAE | 4 Participants |
| Group 2: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related serious TEAE | 0 Participants |
| Group 2: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE leading to treatment discontinuation | 0 Participants |
| Group 2: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE leading to treatment discontinuation | 0 Participants |
| Group 2: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE leading to death | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE leading to treatment discontinuation | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE | 1 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE ≥ grade 3 | 1 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE ≥ grade 3 | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE leading to treatment discontinuation | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related serious TEAE | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any serious TEAE | 1 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE leading to death | 1 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE of special interest | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE of special interest | 0 Participants |
| Group 3: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE leading to death | 0 Participants |
| Group 3: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any serious TEAE | 1 Participants |
| Group 3: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE of special interest | 0 Participants |
| Group 3: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related serious TEAE | 0 Participants |
| Group 3: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE ≥ grade 3 | 0 Participants |
| Group 3: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE leading to treatment discontinuation | 0 Participants |
| Group 3: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE ≥ grade 3 | 1 Participants |
| Group 3: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE leading to death | 0 Participants |
| Group 3: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE leading to treatment discontinuation | 0 Participants |
| Group 3: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE | 0 Participants |
| Group 3: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE leading to death | 1 Participants |
| Group 3: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE | 1 Participants |
| Group 3: Control | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE of special interest | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any serious TEAE | 2 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE ≥ grade 3 | 1 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related serious TEAE | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE leading to death | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE leading to death | 1 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE | 7 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE of special interest | 4 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE ≥ grade 3 | 4 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE of special interest | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE leading to treatment discontinuation | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any TEAE leading to treatment discontinuation | 0 Participants |
| Group 4: Plitidepsin 2.5 mg | Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) | Any treatment-related TEAE | 2 Participants |
Secondary
Time to Confirmed Negativisation in SARS-CoV-2 Antigen Test or Real Time Polymerase Chain Reaction (RT-PCR) Cycle Threshold (Ct) > 30
Time to confirmed negativisation in SARS-CoV antigen test or RT-PCR Ct\>30 was calculated as time from randomisation to the corresponding event using Kaplan-Meier (KM) estimates. Participants with no available data for any time to event efficacy endpoint were censored at time 0, end of study (Day 60 ±3), or date of early study termination. Also, participants who had not achieved the time to event endpoint were censored at the last valid assessment.
Time frame: Day 1 to Day 60 (±3)
Population: FAS Population: All randomised participants who received at least 1 dose of study treatment (plitidepsin or control) and completed follow-up for survival until Day 30 (±2). Participants who died before the end of the follow-up period were also included in the FAS population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1: Plitidepsin 2.5 mg | Time to Confirmed Negativisation in SARS-CoV-2 Antigen Test or Real Time Polymerase Chain Reaction (RT-PCR) Cycle Threshold (Ct) > 30 | 61.0 days |
| Group 1: Control | Time to Confirmed Negativisation in SARS-CoV-2 Antigen Test or Real Time Polymerase Chain Reaction (RT-PCR) Cycle Threshold (Ct) > 30 | 2.0 days |
| Group 2: Plitidepsin 2.5 mg | Time to Confirmed Negativisation in SARS-CoV-2 Antigen Test or Real Time Polymerase Chain Reaction (RT-PCR) Cycle Threshold (Ct) > 30 | 14.0 days |
| Group 2: Control | Time to Confirmed Negativisation in SARS-CoV-2 Antigen Test or Real Time Polymerase Chain Reaction (RT-PCR) Cycle Threshold (Ct) > 30 | 14.0 days |
| Group 3: Plitidepsin 2.5 mg | Time to Confirmed Negativisation in SARS-CoV-2 Antigen Test or Real Time Polymerase Chain Reaction (RT-PCR) Cycle Threshold (Ct) > 30 | 13.0 days |
| Group 3: Control | Time to Confirmed Negativisation in SARS-CoV-2 Antigen Test or Real Time Polymerase Chain Reaction (RT-PCR) Cycle Threshold (Ct) > 30 | 10.0 days |
| Group 4: Plitidepsin 2.5 mg | Time to Confirmed Negativisation in SARS-CoV-2 Antigen Test or Real Time Polymerase Chain Reaction (RT-PCR) Cycle Threshold (Ct) > 30 | 14.0 days |
Secondary
Time to Sustained Discontinuation of Oxygen Supplementation
Time to sustained discontinuation is calculated as time from randomisation to the corresponding event using KM estimates. Corresponding events were defined as discontinuation of oxygen supplementation for at least 7 days. Participants with no available data for any time to event efficacy endpoint were censored at time 0, end of study (Day 60 ±3), or date of early study termination. Also, participants who had not achieved the time to event endpoint were censored at the last valid assessment.
Time frame: Day 1 to Day 60 (±3)
Population: FAS Population: All randomised participants who received at least 1 dose of study treatment (plitidepsin or control) and completed follow-up for survival until Day 30 (±2). Participants who died before the end of the follow-up period were also included in the FAS population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1: Plitidepsin 2.5 mg | Time to Sustained Discontinuation of Oxygen Supplementation | 13.0 days |
| Group 1: Control | Time to Sustained Discontinuation of Oxygen Supplementation | NA days |
| Group 2: Plitidepsin 2.5 mg | Time to Sustained Discontinuation of Oxygen Supplementation | 63.0 days |
| Group 2: Control | Time to Sustained Discontinuation of Oxygen Supplementation | NA days |
| Group 3: Plitidepsin 2.5 mg | Time to Sustained Discontinuation of Oxygen Supplementation | NA days |
| Group 3: Control | Time to Sustained Discontinuation of Oxygen Supplementation | 14.0 days |
| Group 4: Plitidepsin 2.5 mg | Time to Sustained Discontinuation of Oxygen Supplementation | 14.0 days |
Secondary
Time to Sustained End of COVID-related Hospital Care
Time to sustained end of COVID-related hospital care from the time of randomisation was calculated as time from randomisation to the corresponding event using KM estimates. Participants with no available data for any time to event efficacy endpoint were censored at time 0, end of study (Day 60 ±3), or date of early study termination. Also, participants who had not achieved the time to event endpoint were censored at the last valid assessment.
Time frame: Day 1 to Day 60 (±3)
Population: FAS Population: All randomised participants who received at least 1 dose of study treatment (plitidepsin or control) and completed follow-up for survival until Day 30 (±2). Participants who died before the end of the follow-up period were also included in the FAS population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1: Plitidepsin 2.5 mg | Time to Sustained End of COVID-related Hospital Care | 20.5 days |
| Group 1: Control | Time to Sustained End of COVID-related Hospital Care | 4.0 days |
| Group 2: Plitidepsin 2.5 mg | Time to Sustained End of COVID-related Hospital Care | 4.5 days |
| Group 2: Control | Time to Sustained End of COVID-related Hospital Care | 37.0 days |
| Group 3: Plitidepsin 2.5 mg | Time to Sustained End of COVID-related Hospital Care | 24.0 days |
| Group 3: Control | Time to Sustained End of COVID-related Hospital Care | 2.0 days |
| Group 4: Plitidepsin 2.5 mg | Time to Sustained End of COVID-related Hospital Care | 7.0 days |
Secondary
Time to Sustained Improvement and Resolution of Selected COVID-19 Signs/Symptoms
Time to sustained improvement and resolution of all targeted COVID-19 signs/symptoms was calculated as time from randomisation to the corresponding event using KM estimates. Corresponding events were defined as the event occurring on the first of 4 consecutive days when all symptoms scored as National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v5.0; category of moderate-severe intensity, or requiring medical intervention, or limiting instrumental activity of daily living are scored as mild or absent AND all symptoms scored mild or 0 (absent) at study entry are scored as 0. Participants with no available data for any time to event efficacy endpoint were censored at time 0, end of study (Day 60 ±3), or date of early study termination. Also, participants who had not achieved the time to event endpoint were censored at the last valid assessment.
Time frame: Day 1 to Day 60 (±3)
Population: FAS Population: All randomised participants who received at least 1 dose of study treatment (plitidepsin or control) and completed follow-up for survival until Day 30 (±2). Participants who died before the end of the follow-up period were also included in the FAS population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Group 1: Plitidepsin 2.5 mg | Time to Sustained Improvement and Resolution of Selected COVID-19 Signs/Symptoms | NA days |
| Group 1: Control | Time to Sustained Improvement and Resolution of Selected COVID-19 Signs/Symptoms | NA days |
| Group 2: Plitidepsin 2.5 mg | Time to Sustained Improvement and Resolution of Selected COVID-19 Signs/Symptoms | NA days |
| Group 2: Control | Time to Sustained Improvement and Resolution of Selected COVID-19 Signs/Symptoms | 14.0 days |
| Group 3: Plitidepsin 2.5 mg | Time to Sustained Improvement and Resolution of Selected COVID-19 Signs/Symptoms | 17.0 days |
| Group 3: Control | Time to Sustained Improvement and Resolution of Selected COVID-19 Signs/Symptoms | 2.0 days |
| Group 4: Plitidepsin 2.5 mg | Time to Sustained Improvement and Resolution of Selected COVID-19 Signs/Symptoms | 37.0 days |