Trial Outcomes & Findings for Trial to Determine the Efficacy/Safety of Plitidepsin vs Control in Patients With Moderate COVID-19 Infection (NCT NCT04784559)

Last Updated: 2025-02-21

Results Overview

Time to sustained withdrawal of oxygen supplementation (in days) with no subsequent reutilisation during remaining study period is defined as the first day, from randomisation through completion of the study, on which a patient i. satisfies categories 0 to 4 on the 11-point WHO Clinical Progression Scale, and ii. has no subsequent reutilisation of oxygen supplementation (5 to 10 on the 11-point WHO Clinical Progression Scale). The WHO clinical progression scale provides a measure of illness severity across a range from 0 (uninfected) to 10 (dead).

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

205 participants

Primary outcome timeframe

From administration date to Day 31(±3)

Results posted on

2025-02-21

Participant Flow

Participant milestones

Participant milestones
Measure	Plitidepsin 2.5 mg Arm Participants received plitidepsin 2.5 mg/day intravenous (IV) in addition to dexamethasone on days 1 to 3.	Plitidepsin 1.5 mg Arm Participants received plitidepsin 1.5 mg/day IV in addition to dexamethasone on days 1 to 3.	Control Arm Participants received dexamethasone IV on Days 1 to 3. Additionally, in accordance with local treatment guidelines, participants in this group may have received a regulatory-approved antiviral treatment.
Overall Study STARTED	68	70	67
Overall Study COMPLETED	60	64	61
Overall Study NOT COMPLETED	8	6	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Plitidepsin 2.5 mg Arm Participants received plitidepsin 2.5 mg/day intravenous (IV) in addition to dexamethasone on days 1 to 3.	Plitidepsin 1.5 mg Arm Participants received plitidepsin 1.5 mg/day IV in addition to dexamethasone on days 1 to 3.	Control Arm Participants received dexamethasone IV on Days 1 to 3. Additionally, in accordance with local treatment guidelines, participants in this group may have received a regulatory-approved antiviral treatment.
Overall Study Withdrawal by Subject	3	2	1
Overall Study Death	2	1	2
Overall Study Lost to Follow-up	0	0	2
Overall Study Participant worsened, PI decision	1	0	0
Overall Study Participant deterioration becoming a candidate for treatment with TZB	1	0	0
Overall Study Participant admitted in other hospital due to a serious adverse event	1	0	0
Overall Study Did not meet all inclusion criteria	0	1	0
Overall Study The participant was transferred to IRCU	0	1	0
Overall Study SAE	0	1	0
Overall Study Discontinued as was found to be ineligible	0	0	1

Baseline Characteristics

Only females. Percentages were calculated based on the number of females per group as the denominator

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Plitidepsin 2.5 mg Arm n=68 Participants Participants received plitidepsin 2.5 mg/day intravenous (IV) in addition to dexamethasone on days 1 to 3.	Plitidepsin 1.5 mg Arm n=70 Participants Participants received plitidepsin 1.5 mg/day IV in addition to dexamethasone on days 1 to 3.	Control Arm n=67 Participants Participants received dexamethasone IV on Days 1 to 3. Additionally, in accordance with local treatment guidelines, participants in this group may have received a regulatory-approved antiviral treatment.	Total n=205 Participants Total of all reporting groups
Age, Continuous	58.9 years STANDARD_DEVIATION 13.33 • n=68 Participants	58.1 years STANDARD_DEVIATION 14.80 • n=70 Participants	59.3 years STANDARD_DEVIATION 15.02 • n=67 Participants	58.7 years STANDARD_DEVIATION 14.34 • n=205 Participants
Age, Customized ≥18 to 59 years	32 Participants n=68 Participants	34 Participants n=70 Participants	32 Participants n=67 Participants	98 Participants n=205 Participants
Age, Customized ≥60 to 64 years	13 Participants n=68 Participants	9 Participants n=70 Participants	6 Participants n=67 Participants	28 Participants n=205 Participants
Age, Customized ≥65 to 69 years	8 Participants n=68 Participants	11 Participants n=70 Participants	11 Participants n=67 Participants	30 Participants n=205 Participants
Age, Customized ≥70 to 74 years	9 Participants n=68 Participants	8 Participants n=70 Participants	4 Participants n=67 Participants	21 Participants n=205 Participants
Age, Customized ≥75 to 79 years	3 Participants n=68 Participants	6 Participants n=70 Participants	7 Participants n=67 Participants	16 Participants n=205 Participants
Age, Customized ≥80 years	3 Participants n=68 Participants	2 Participants n=70 Participants	7 Participants n=67 Participants	12 Participants n=205 Participants
Sex: Female, Male Female	25 Participants n=68 Participants	26 Participants n=70 Participants	25 Participants n=67 Participants	76 Participants n=205 Participants
Sex: Female, Male Male	43 Participants n=68 Participants	44 Participants n=70 Participants	42 Participants n=67 Participants	129 Participants n=205 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	33 Participants n=68 Participants	35 Participants n=70 Participants	21 Participants n=67 Participants	89 Participants n=205 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	35 Participants n=68 Participants	35 Participants n=70 Participants	46 Participants n=67 Participants	116 Participants n=205 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=68 Participants	0 Participants n=70 Participants	0 Participants n=67 Participants	0 Participants n=205 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=68 Participants	0 Participants n=70 Participants	0 Participants n=67 Participants	0 Participants n=205 Participants
Race (NIH/OMB) Asian	1 Participants n=68 Participants	3 Participants n=70 Participants	0 Participants n=67 Participants	4 Participants n=205 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=68 Participants	0 Participants n=70 Participants	0 Participants n=67 Participants	0 Participants n=205 Participants
Race (NIH/OMB) Black or African American	0 Participants n=68 Participants	0 Participants n=70 Participants	0 Participants n=67 Participants	0 Participants n=205 Participants
Race (NIH/OMB) White	63 Participants n=68 Participants	62 Participants n=70 Participants	64 Participants n=67 Participants	189 Participants n=205 Participants
Race (NIH/OMB) More than one race	4 Participants n=68 Participants	5 Participants n=70 Participants	3 Participants n=67 Participants	12 Participants n=205 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=68 Participants	0 Participants n=70 Participants	0 Participants n=67 Participants	0 Participants n=205 Participants
Child-bearing potential, n (%) Yes	4 Participants n=25 Participants • Only females. Percentages were calculated based on the number of females per group as the denominator	5 Participants n=26 Participants • Only females. Percentages were calculated based on the number of females per group as the denominator	4 Participants n=25 Participants • Only females. Percentages were calculated based on the number of females per group as the denominator	13 Participants n=76 Participants • Only females. Percentages were calculated based on the number of females per group as the denominator
Child-bearing potential, n (%) No, surgically sterile/post-menopausal	21 Participants n=25 Participants • Only females. Percentages were calculated based on the number of females per group as the denominator	18 Participants n=26 Participants • Only females. Percentages were calculated based on the number of females per group as the denominator	19 Participants n=25 Participants • Only females. Percentages were calculated based on the number of females per group as the denominator	58 Participants n=76 Participants • Only females. Percentages were calculated based on the number of females per group as the denominator
Child-bearing potential, n (%) No, other	0 Participants n=25 Participants • Only females. Percentages were calculated based on the number of females per group as the denominator	3 Participants n=26 Participants • Only females. Percentages were calculated based on the number of females per group as the denominator	2 Participants n=25 Participants • Only females. Percentages were calculated based on the number of females per group as the denominator	5 Participants n=76 Participants • Only females. Percentages were calculated based on the number of females per group as the denominator
Height at screening	167.79 Centimeter STANDARD_DEVIATION 8.067 • n=66 Participants • Height was not recorded for some participants.	169.56 Centimeter STANDARD_DEVIATION 8.534 • n=67 Participants • Height was not recorded for some participants.	169.25 Centimeter STANDARD_DEVIATION 10.095 • n=65 Participants • Height was not recorded for some participants.	168.87 Centimeter STANDARD_DEVIATION 8.921 • n=198 Participants • Height was not recorded for some participants.
Weight at screening	82.72 kilogram STANDARD_DEVIATION 14.380 • n=68 Participants • weight was not recorded for some participants.	86.05 kilogram STANDARD_DEVIATION 19.778 • n=68 Participants • weight was not recorded for some participants.	87.38 kilogram STANDARD_DEVIATION 19.672 • n=66 Participants • weight was not recorded for some participants.	85.36 kilogram STANDARD_DEVIATION 18.120 • n=202 Participants • weight was not recorded for some participants.
Body mass index at screening	29.45 kg/m^2 STANDARD_DEVIATION 4.555 • n=66 Participants • not recorded for some participants	29.68 kg/m^2 STANDARD_DEVIATION 5.617 • n=67 Participants • not recorded for some participants	30.26 kg/m^2 STANDARD_DEVIATION 6.116 • n=65 Participants • not recorded for some participants	29.79 kg/m^2 STANDARD_DEVIATION 5.448 • n=198 Participants • not recorded for some participants
Body mass index group at screening ≥18.5 and <25 kg/m^2	10 Participants n=68 Participants	10 Participants n=70 Participants	10 Participants n=67 Participants	30 Participants n=205 Participants
Body mass index group at screening ≥25 and <30 kg/m^2	31 Participants n=68 Participants	35 Participants n=70 Participants	26 Participants n=67 Participants	92 Participants n=205 Participants
Body mass index group at screening ≥30 and <35 kg/m^2	15 Participants n=68 Participants	13 Participants n=70 Participants	17 Participants n=67 Participants	45 Participants n=205 Participants
Body mass index group at screening ≥35 and <40 kg/m^2	9 Participants n=68 Participants	4 Participants n=70 Participants	8 Participants n=67 Participants	21 Participants n=205 Participants
Body mass index group at screening ≥40 kg/m^2	1 Participants n=68 Participants	5 Participants n=70 Participants	4 Participants n=67 Participants	10 Participants n=205 Participants
Body mass index group at screening Missing	2 Participants n=68 Participants	3 Participants n=70 Participants	2 Participants n=67 Participants	7 Participants n=205 Participants
Body surface area at screening	1.922 m^2 STANDARD_DEVIATION 0.1787 • n=66 Participants • not recorded for some participants	1.961 m^2 STANDARD_DEVIATION 0.2252 • n=67 Participants • not recorded for some participants	1.968 m^2 STANDARD_DEVIATION 0.2299 • n=65 Participants • not recorded for some participants	1.950 m^2 STANDARD_DEVIATION 0.2123 • n=198 Participants • not recorded for some participants
Periods of inclusion Beginning of accrual - August 2021	2 Participants n=68 Participants	1 Participants n=70 Participants	2 Participants n=67 Participants	5 Participants n=205 Participants
Periods of inclusion September 2021 - March 2022	56 Participants n=68 Participants	55 Participants n=70 Participants	51 Participants n=67 Participants	162 Participants n=205 Participants
Periods of inclusion April 2022 - End of accrual	10 Participants n=68 Participants	14 Participants n=70 Participants	14 Participants n=67 Participants	38 Participants n=205 Participants
Systolic blood pressure (mmHg) at screening	123.4 mmHg STANDARD_DEVIATION 18.44 • n=68 Participants	126.9 mmHg STANDARD_DEVIATION 16.25 • n=70 Participants	127.9 mmHg STANDARD_DEVIATION 16.24 • n=67 Participants	126.1 mmHg STANDARD_DEVIATION 17.04 • n=205 Participants
Diastolic blood pressure (mmHg) at screening	74.2 mmHg STANDARD_DEVIATION 9.53 • n=68 Participants	76.1 mmHg STANDARD_DEVIATION 9.36 • n=70 Participants	75.0 mmHg STANDARD_DEVIATION 11.26 • n=67 Participants	75.1 mmHg STANDARD_DEVIATION 10.05 • n=205 Participants
Pulse rate (beats/min) at screening	81.6 beats/min STANDARD_DEVIATION 13.72 • n=68 Participants	83.9 beats/min STANDARD_DEVIATION 11.36 • n=70 Participants	84.2 beats/min STANDARD_DEVIATION 13.50 • n=67 Participants	83.2 beats/min STANDARD_DEVIATION 12.88 • n=205 Participants
Temperature (C) at screening	36.91 celsius STANDARD_DEVIATION 0.878 • n=68 Participants • Data not available for all participants in this cohort	36.90 celsius STANDARD_DEVIATION 0.899 • n=70 Participants • Data not available for all participants in this cohort	36.92 celsius STANDARD_DEVIATION 0.875 • n=66 Participants • Data not available for all participants in this cohort	36.91 celsius STANDARD_DEVIATION 0.880 • n=204 Participants • Data not available for all participants in this cohort
Respiration rate (breaths/min) at screening	19.5 breaths/min STANDARD_DEVIATION 3.49 • n=68 Participants • Data not available for all participants in this cohort	19.0 breaths/min STANDARD_DEVIATION 3.40 • n=69 Participants • Data not available for all participants in this cohort	19.9 breaths/min STANDARD_DEVIATION 3.32 • n=65 Participants • Data not available for all participants in this cohort	19.4 breaths/min STANDARD_DEVIATION 3.41 • n=202 Participants • Data not available for all participants in this cohort
Oxygen saturation (%) at screening	96.29 Percentage STANDARD_DEVIATION 1.779 • n=68 Participants • Data not available for all participants in this cohort	96.26 Percentage STANDARD_DEVIATION 1.721 • n=69 Participants • Data not available for all participants in this cohort	96.44 Percentage STANDARD_DEVIATION 1.749 • n=67 Participants • Data not available for all participants in this cohort	96.33 Percentage STANDARD_DEVIATION 1.743 • n=204 Participants • Data not available for all participants in this cohort
Fraction of inspired oxygen (%) at screening	26.92 Percentage STANDARD_DEVIATION 3.861 • n=68 Participants	26.91 Percentage STANDARD_DEVIATION 3.370 • n=70 Participants	27.94 Percentage STANDARD_DEVIATION 9.526 • n=67 Participants	27.25 Percentage STANDARD_DEVIATION 6.191 • n=205 Participants
Vaccination status Fully vaccinated	35 Participants n=68 Participants	36 Participants n=70 Participants	32 Participants n=67 Participants	103 Participants n=205 Participants
Vaccination status Non-fully vaccinated	6 Participants n=68 Participants	3 Participants n=70 Participants	4 Participants n=67 Participants	13 Participants n=205 Participants
Vaccination status Not vaccinated	27 Participants n=68 Participants	31 Participants n=70 Participants	31 Participants n=67 Participants	89 Participants n=205 Participants
Vaccination status Fully vaccinated + Non-fully vaccinated	41 Participants n=68 Participants	39 Participants n=70 Participants	36 Participants n=67 Participants	116 Participants n=205 Participants
SARS-CoV-2 viral load at Day 1	5.02 log10 copies/mL STANDARD_DEVIATION 1.880 • n=47 Participants • Summary was based on full analysis set	4.97 log10 copies/mL STANDARD_DEVIATION 1.985 • n=56 Participants • Summary was based on full analysis set	5.06 log10 copies/mL STANDARD_DEVIATION 2.253 • n=55 Participants • Summary was based on full analysis set	5.01 log10 copies/mL STANDARD_DEVIATION 2.040 • n=158 Participants • Summary was based on full analysis set

PRIMARY outcome

Timeframe: From administration date to Day 31(±3)

Population: Intent-to-treat Population

Outcome measures

Outcome measures
Measure	Plitidepsin 2.5 mg Arm n=68 Participants Participants received plitidepsin 2.5 mg/day intravenous (IV) in addition to dexamethasone on days 1 to 3.	Plitidepsin 1.5 mg Arm n=70 Participants Participants received plitidepsin 1.5 mg/day IV in addition to dexamethasone on days 1 to 3.	Control Arm n=67 Participants Participants received dexamethasone IV on Days 1 to 3. Additionally, in accordance with local treatment guidelines, participants in this group may have received a regulatory-approved antiviral treatment.
Time to Sustained Withdrawal of Supplementary Oxygen With no Subsequent Reutilisation During Remaining Study Period	5 Days Interval 4.0 to 7.0	5 Days Interval 4.0 to 6.0	7 Days Interval 6.0 to 8.0

SECONDARY outcome

Timeframe: From administration date to Day 31(±3)

Population: Intent-to-treat Population

Time to sustained (i.e., with no subsequent readmission to Day 31) hospital discharge (since randomization)

Outcome measures

Outcome measures
Measure	Plitidepsin 2.5 mg Arm n=68 Participants Participants received plitidepsin 2.5 mg/day intravenous (IV) in addition to dexamethasone on days 1 to 3.	Plitidepsin 1.5 mg Arm n=70 Participants Participants received plitidepsin 1.5 mg/day IV in addition to dexamethasone on days 1 to 3.	Control Arm n=67 Participants Participants received dexamethasone IV on Days 1 to 3. Additionally, in accordance with local treatment guidelines, participants in this group may have received a regulatory-approved antiviral treatment.
Time to Sustained (i.e., With no Subsequent Readmission to Day 31) Hospital Discharge (Since Randomisation).	7 Days Interval 7.0 to 9.0	7 Days NA explanation: Variability in participants with or without hospital events is insufficient to calculate the lower and upper CI	7 Days Interval 7.0 to 9.0

SECONDARY outcome

Timeframe: Day 8 (±1)

Population: Full analysis set

The WHO clinical progression scale provides a measure of illness severity across a range from 0 (uninfected) to 10 (dead). 0 = Uninfected; no viral RNA detected 1. = Ambulatory mild disease. Asymptomatic; viral RNA detected 2. = Ambulatory mild disease. Symptomatic; independent 3. = Ambulatory mild disease. Symptomatic; assistance needed 4. = Hospitalized: moderate disease. Hospitalized; no oxygen therapy 5. = Hospitalized: moderate disease. Hospitalized; oxygen by mask or nasal prongs 6. = Hospitalized: severe diseases. Hospitalized; oxygen by NIV or high flow 7. = Hospitalized: severe diseases. Intubation and mechanical ventilation pO2/FIO2 \> 150 or SpO2/FIO2 \> 200 8. = Hospitalized: severe diseases. Mechanical ventilation pO2 /FIO2 \<150 (SpO2 /FiO2 \<200) or vasopressors 9. = Hospitalized: severe diseases. Mechanical ventilation pO2 /FiO2 \<150 and vasopressors, dialysis, or ECMO 10. = dead

Outcome measures

Outcome measures
Measure	Plitidepsin 2.5 mg Arm n=63 Participants Participants received plitidepsin 2.5 mg/day intravenous (IV) in addition to dexamethasone on days 1 to 3.	Plitidepsin 1.5 mg Arm n=67 Participants Participants received plitidepsin 1.5 mg/day IV in addition to dexamethasone on days 1 to 3.	Control Arm n=65 Participants Participants received dexamethasone IV on Days 1 to 3. Additionally, in accordance with local treatment guidelines, participants in this group may have received a regulatory-approved antiviral treatment.
Clinical Status by the 11-category WHO Clinical Progression Scale on Day 8 0 = uninfected, no viral RNA detected	6 Participants	10 Participants	3 Participants
Clinical Status by the 11-category WHO Clinical Progression Scale on Day 8 1 = asymptomatic, viral RNA detected	12 Participants	15 Participants	12 Participants
Clinical Status by the 11-category WHO Clinical Progression Scale on Day 8 2 = symptomatic, independent	20 Participants	17 Participants	19 Participants
Clinical Status by the 11-category WHO Clinical Progression Scale on Day 8 3 = symptomatic, assistance needed	0 Participants	1 Participants	1 Participants
Clinical Status by the 11-category WHO Clinical Progression Scale on Day 8 4 = hospitalised, no oxygen therapy	4 Participants	8 Participants	7 Participants
Clinical Status by the 11-category WHO Clinical Progression Scale on Day 8 5 = hospitalised, oxygen by mask or nasal prongs	10 Participants	8 Participants	20 Participants
Clinical Status by the 11-category WHO Clinical Progression Scale on Day 8 6 = hospitalised, oxygen by NIV or high flow	5 Participants	7 Participants	1 Participants
Clinical Status by the 11-category WHO Clinical Progression Scale on Day 8 7 = intubation and mechanical ventilation. pO2/FiO2 >150 or SpO2/FiO2 >200	4 Participants	1 Participants	2 Participants
Clinical Status by the 11-category WHO Clinical Progression Scale on Day 8 8 = mechanical ventilation pO2/FiO2 <150 (SpO2/FiO2 <200) or vasopressors	1 Participants	0 Participants	0 Participants
Clinical Status by the 11-category WHO Clinical Progression Scale on Day 8 9 = mechanical ventilation pO2/FiO2 <150 and vasopressors, dialysis, or ECMO	0 Participants	0 Participants	0 Participants
Clinical Status by the 11-category WHO Clinical Progression Scale on Day 8 10 = dead	1 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: From administration date to Day 31(±3)

Population: Full Analysis Set; number of participants who received advanced oxygen support are presented

Total duration of advanced oxygen support (high-flow nasal oxygen, extracorporeal membrane oxygenation -ECMO-, non-invasive ventilation or mechanical ventilation).

Outcome measures

Outcome measures
Measure	Plitidepsin 2.5 mg Arm n=13 Participants Participants received plitidepsin 2.5 mg/day intravenous (IV) in addition to dexamethasone on days 1 to 3.	Plitidepsin 1.5 mg Arm n=11 Participants Participants received plitidepsin 1.5 mg/day IV in addition to dexamethasone on days 1 to 3.	Control Arm n=11 Participants Participants received dexamethasone IV on Days 1 to 3. Additionally, in accordance with local treatment guidelines, participants in this group may have received a regulatory-approved antiviral treatment.
Total Duration of Advanced Oxygen Support	12.2 Days Standard Deviation 9.71	10 Days Standard Deviation 8.21	8.3 Days Standard Deviation 12.66

SECONDARY outcome

Timeframe: Day 4, Day 8(±1) , Day 15(±1) and Day 31(±3)

Population: Full Analysis Set

Number of participants in each study group requiring admission to intensive care unit

Outcome measures

Outcome measures
Measure	Plitidepsin 2.5 mg Arm n=63 Participants Participants received plitidepsin 2.5 mg/day intravenous (IV) in addition to dexamethasone on days 1 to 3.	Plitidepsin 1.5 mg Arm n=67 Participants Participants received plitidepsin 1.5 mg/day IV in addition to dexamethasone on days 1 to 3.	Control Arm n=65 Participants Participants received dexamethasone IV on Days 1 to 3. Additionally, in accordance with local treatment guidelines, participants in this group may have received a regulatory-approved antiviral treatment.
Number of Participants in Each Study Group Requiring Admission to ICU From Day 1 to Day 31	7 participants Interval 4.59 to 21.6	5 participants Interval 2.47 to 16.6	4 participants Interval 1.7 to 15.0
Number of Participants in Each Study Group Requiring Admission to ICU From Day 1 to Day 4	1 participants Interval 0.0402 to 8.53	1 participants Interval 0.0378 to 8.04	3 participants Interval 0.962 to 12.9
Number of Participants in Each Study Group Requiring Admission to ICU From Day 1 to Day 8	7 participants Interval 4.59 to 21.6	3 participants Interval 0.933 to 12.5	4 participants Interval 1.7 to 15.0
Number of Participants in Each Study Group Requiring Admission to ICU From Day 1 to Day 15	7 participants Interval 4.59 to 21.6	4 participants Interval 1.65 to 14.6	4 participants Interval 1.7 to 15.0

SECONDARY outcome

Timeframe: From administration date to Day 31(±3)

Population: As Treated Population

Adverse Event Types according to the National Cancer Institute \[NCI\]-Common Terminology Criteria for AEs (CTCAE v.5.0): The number of participants who experienced treatment-emergent adverse events (TEAEs) are presented.

Outcome measures

Outcome measures
Measure	Plitidepsin 2.5 mg Arm n=63 Participants Participants received plitidepsin 2.5 mg/day intravenous (IV) in addition to dexamethasone on days 1 to 3.	Plitidepsin 1.5 mg Arm n=67 Participants Participants received plitidepsin 1.5 mg/day IV in addition to dexamethasone on days 1 to 3.	Control Arm n=65 Participants Participants received dexamethasone IV on Days 1 to 3. Additionally, in accordance with local treatment guidelines, participants in this group may have received a regulatory-approved antiviral treatment.
Frequency of Adverse Events	45 Participants	44 Participants	40 Participants

SECONDARY outcome

Timeframe: From administration date to Day 31(±3)

Population: As Treated Population

Frequency of treatment-emergent adverse events (TEAEs) of ≥grade 3 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE, version 5.0), TEAEs of special interest, serious TEAEs, serious treatment-related TEAEs, TEAEs leading to treatment discontinuation, and deaths

Outcome measures

Outcome measures
Measure	Plitidepsin 2.5 mg Arm n=63 Participants Participants received plitidepsin 2.5 mg/day intravenous (IV) in addition to dexamethasone on days 1 to 3.	Plitidepsin 1.5 mg Arm n=67 Participants Participants received plitidepsin 1.5 mg/day IV in addition to dexamethasone on days 1 to 3.	Control Arm n=65 Participants Participants received dexamethasone IV on Days 1 to 3. Additionally, in accordance with local treatment guidelines, participants in this group may have received a regulatory-approved antiviral treatment.
Frequency of TEAEs of ≥Grade 3 According to NCI-CTCAE for Adverse Events (Version 5.0), TEAEs of Special Interest, Serious TEAEs, Serious Treatment-related TEAEs, TEAEs Leading to Treatment Discontinuation, and Deaths Any TEAE leading to discontinuation of any study treatment	1 Participants	1 Participants	1 Participants
Frequency of TEAEs of ≥Grade 3 According to NCI-CTCAE for Adverse Events (Version 5.0), TEAEs of Special Interest, Serious TEAEs, Serious Treatment-related TEAEs, TEAEs Leading to Treatment Discontinuation, and Deaths Any TEAE leading to death	2 Participants	1 Participants	2 Participants
Frequency of TEAEs of ≥Grade 3 According to NCI-CTCAE for Adverse Events (Version 5.0), TEAEs of Special Interest, Serious TEAEs, Serious Treatment-related TEAEs, TEAEs Leading to Treatment Discontinuation, and Deaths Any TEAE Grade ≥3	22 Participants	17 Participants	11 Participants
Frequency of TEAEs of ≥Grade 3 According to NCI-CTCAE for Adverse Events (Version 5.0), TEAEs of Special Interest, Serious TEAEs, Serious Treatment-related TEAEs, TEAEs Leading to Treatment Discontinuation, and Deaths Any TEAE of special interest	22 Participants	25 Participants	18 Participants
Frequency of TEAEs of ≥Grade 3 According to NCI-CTCAE for Adverse Events (Version 5.0), TEAEs of Special Interest, Serious TEAEs, Serious Treatment-related TEAEs, TEAEs Leading to Treatment Discontinuation, and Deaths Any serious TEAE	11 Participants	6 Participants	5 Participants
Frequency of TEAEs of ≥Grade 3 According to NCI-CTCAE for Adverse Events (Version 5.0), TEAEs of Special Interest, Serious TEAEs, Serious Treatment-related TEAEs, TEAEs Leading to Treatment Discontinuation, and Deaths Any serious treatment-related TEAE to any study treatment	1 Participants	1 Participants	0 Participants

Adverse Events

Plitidepsin 2.5 mg Arm

Serious events: 11 serious events

Other events: 43 other events

Deaths: 2 deaths

Plitidepsin 1.5 mg Arm

Serious events: 6 serious events

Other events: 43 other events

Deaths: 1 deaths

Control Arm

Serious events: 5 serious events

Other events: 38 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Development Virology Business Unit

PharmaMar

Phone: +34 918466000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Plitidepsin 2.5 mg Arm n=63 participants at risk Participants received plitidepsin 2.5 mg/day intravenous (IV) in addition to dexamethasone on days 1 to 3.	Plitidepsin 1.5 mg Arm n=67 participants at risk Participants received plitidepsin 1.5 mg/day IV in addition to dexamethasone on days 1 to 3.	Control Arm n=65 participants at risk Participants received dexamethasone IV on Days 1 to 3. Additionally, in accordance with local treatment guidelines, participants in this group may have received a regulatory-approved antiviral treatment.
Gastrointestinal disorders Intestinal ischaemia	0.00% 0/63 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/65 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
General disorders Multiple organ dysfunction syndrome	1.6% 1/63 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/65 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Immune system disorders Hypersensitivity	1.6% 1/63 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Infections and infestations COVID-19 pneumonia	1.6% 1/63 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	3.1% 2/65 • Number of events 2 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Infections and infestations Sepsis	3.2% 2/63 • Number of events 2 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Infections and infestations Bronchopulmonary aspergillosis	1.6% 1/63 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Infections and infestations COVID-19	0.00% 0/63 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/65 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Infections and infestations Cellulitis	0.00% 0/63 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 2 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Infections and infestations Pneumonia	1.6% 1/63 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Infections and infestations Pneumonia pseudomonal	1.6% 1/63 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Infections and infestations Pneumonia streptococcal	0.00% 0/63 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/65 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Infections and infestations Staphylococcal sepsis	0.00% 0/63 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Respiratory, thoracic and mediastinal disorders Respiratory failure	9.5% 6/63 • Number of events 7 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	6.0% 4/67 • Number of events 5 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	3.1% 2/65 • Number of events 2 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	1.6% 1/63 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/65 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	1.6% 1/63 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/63 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Vascular disorders Deep vein thrombosis	1.6% 1/63 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.

Other adverse events
Measure	Plitidepsin 2.5 mg Arm n=63 participants at risk Participants received plitidepsin 2.5 mg/day intravenous (IV) in addition to dexamethasone on days 1 to 3.	Plitidepsin 1.5 mg Arm n=67 participants at risk Participants received plitidepsin 1.5 mg/day IV in addition to dexamethasone on days 1 to 3.	Control Arm n=65 participants at risk Participants received dexamethasone IV on Days 1 to 3. Additionally, in accordance with local treatment guidelines, participants in this group may have received a regulatory-approved antiviral treatment.
Metabolism and nutrition disorders Hypocalcaemia	1.6% 1/63 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Metabolism and nutrition disorders Hypomagnesaemia	1.6% 1/63 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Metabolism and nutrition disorders Hypoproteinaemia	1.6% 1/63 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Metabolism and nutrition disorders Metabolic alkalosis	1.6% 1/63 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Renal and urinary disorders Dysuria	1.6% 1/63 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Renal and urinary disorders Pollakiuria	0.00% 0/63 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/65 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Musculoskeletal and connective tissue disorders Myalgia	6.3% 4/63 • Number of events 5 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	3.0% 2/67 • Number of events 2 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/65 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Musculoskeletal and connective tissue disorders Back pain	3.2% 2/63 • Number of events 2 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	3.0% 2/67 • Number of events 2 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/65 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Musculoskeletal and connective tissue disorders Pain in extremity	3.2% 2/63 • Number of events 2 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	3.0% 2/67 • Number of events 2 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Musculoskeletal and connective tissue disorders Myopathy	3.2% 2/63 • Number of events 2 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/65 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Musculoskeletal and connective tissue disorders Limb discomfort	1.6% 1/63 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Musculoskeletal and connective tissue disorders Muscle contracture	0.00% 0/63 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 2 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/63 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/65 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Renal and urinary disorders Urge incontinence	1.6% 1/63 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acrochordon	0.00% 0/63 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thymoma	0.00% 0/63 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/65 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Nervous system disorders Headache	9.5% 6/63 • Number of events 8 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	10.4% 7/67 • Number of events 8 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	7.7% 5/65 • Number of events 5 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Nervous system disorders Dizziness	1.6% 1/63 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	3.0% 2/67 • Number of events 2 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Nervous system disorders Paraesthesia	0.00% 0/63 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/65 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Nervous system disorders Epilepsy	1.6% 1/63 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Nervous system disorders Neuromyopathy	0.00% 0/63 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Nervous system disorders Psychomotor hyperactivity	0.00% 0/63 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Nervous system disorders Somnolence	0.00% 0/63 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Nervous system disorders Tremor	1.6% 1/63 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Psychiatric disorders Sleep disorder	11.1% 7/63 • Number of events 8 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	9.0% 6/67 • Number of events 6 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	7.7% 5/65 • Number of events 6 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Psychiatric disorders Anxiety	7.9% 5/63 • Number of events 6 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/65 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Psychiatric disorders Confusional state	3.2% 2/63 • Number of events 2 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Psychiatric disorders Irritability	1.6% 1/63 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Psychiatric disorders Delirium	1.6% 1/63 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Renal and urinary disorders Renal impairment	6.3% 4/63 • Number of events 4 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/65 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Metabolism and nutrition disorders Hypernatraemia	0.00% 0/63 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/67 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/65 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Blood and lymphatic system disorders Lymphopenia	3.2% 2/63 • Number of events 2 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 2 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/65 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Blood and lymphatic system disorders Leukocytosis	0.00% 0/63 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	3.1% 2/65 • Number of events 2 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Blood and lymphatic system disorders Anaemia	1.6% 1/63 • Number of events 2 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Blood and lymphatic system disorders Leukopenia	0.00% 0/63 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/65 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Blood and lymphatic system disorders Neutropenia	0.00% 0/63 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Blood and lymphatic system disorders Normocytic anaemia	0.00% 0/63 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Cardiac disorders Bradycardia	3.2% 2/63 • Number of events 2 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/65 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Cardiac disorders Atrioventricular block	0.00% 0/63 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	3.0% 2/67 • Number of events 2 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	0.00% 0/65 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.
Cardiac disorders Tachycardia	0.00% 0/63 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/67 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.	1.5% 1/65 • Number of events 1 • From Screening to Day 31 +/- 3 days As pre-specified in the approved Protocol and Statistical Analysis Plan of the study "Safety analyses will be based on the As Treated Population." Adverse events of participants not belonging to the as-treated population: One randomized participant in Plitidepsin 1.5 mg arm, that never received any study treatment, experienced an AE of adult respiratory distress syndrome.