COVID-19
Conditions
Keywords
Plitidepsin, COVID-19, SARS-COV-2, Coronavirus
Brief summary
In December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia of unknown cause. In a short time, Chinese scientists had shared the genome information of a novel coronavirus (SARS-CoV-2) from these pneumonia patients and developed a real-time reverse transcription PCR (real-time RT-PCR) diagnostic assay. Given no specific antiviral therapy for COVID-19 and the ready availability of plitidepsin as a potential antiviral agent, based on pre-clinical studies, this randomized, parallel and proof of concept trial will evaluate the safety of three doses of plitidepsin in patients hospitalized with COVID-19.
Detailed description
In December 2019, a new infectious respiratory disease emerged in Wuhan, China. The agent that caused this pneumonia was identified as a new virus in the Coronaviridae family (SARS-CoV-2) and the clinical symptomatology associated with the virus has been named COVID-19. COVID-19 is currently a public health emergency. Plitidepsin is an authorized drug in Australia for the treatment of multiple myeloma. Antiviral activity of plitidepsin has been analyzed in a human hepatoma cell line infected with the HCoV-229E-GFP virus, a virus similar to the SARS-CoV-2 virus. Taking into account that the available safety data from plitidepsin comes from patients with solid tumors that received treatment with a regimen of administration of plitidepsin for 5 consecutive days, we propose a multicenter, randomized, proof-of-concept clinical trial to assess the safety profile of 3 different dose levels of plitidepsin administered three consecutive days, in adult patients with confirmed diagnosis of COVID-19 who require hospital admission. This study aims to assess safety and toxicity profile and also preliminary efficacy of plitidepsin at each dose level administered according to the proposed administration scheme in patients with COVID-19 who require hospital admission. Main objective is to select the recommended dose levels of plitidepsin for a future phase II / III efficacy study.
Interventions
Plitidepsin 1.5 mg/day will be IV infused through a pump device over 1 hour and 30 minutes, 3 consecutive days. All patients must receive the following prophylactic medications 20-30 minutes before the infusion of plitidepsin: * Diphenhydramine hydrochloride 25 mg iv or equivalent. * Ranitidine 50 mg iv or equivalent. * Dexamethasone 8 mg iv. * Ondansetron 8 mg i.v. 15 minutes infusion or equivalent. * Ondansetron 4 mg p.o. administered every 12 hours until 48 hours after the last administration of plitidepsin.
DRUGPlitidepsin 2.0 mg/day
Plitidepsin 2.0 mg/day will be IV infused through a pump device over 1 hour and 30 minutes, 3 consecutive days. All patients must receive the following prophylactic medications 20-30 minutes before the infusion of plitidepsin: * Diphenhydramine hydrochloride 25 mg iv or equivalent. * Ranitidine 50 mg iv or equivalent. * Dexamethasone 8 mg iv. * Ondansetron 8 mg i.v. 15 minutes infusion or equivalent. * Ondansetron 4 mg p.o. administered every 12 hours until 48 hours after the last administration of plitidepsin.
DRUGPlitidepsin 2.5 mg/day
Plitidepsin 2.5 mg/day will be IV infused through a pump device over 1 hour and 30 minutes, 3 consecutive days. All patients must receive the following prophylactic medications 20-30 minutes before the infusion of plitidepsin: * Diphenhydramine hydrochloride 25 mg iv or equivalent. * Ranitidine 50 mg iv or equivalent. * Dexamethasone 8 mg iv. * Ondansetron 8 mg i.v. 15 minutes infusion or equivalent. * Ondansetron 4 mg p.o. administered every 12 hours until 48 hours after the last administration of plitidepsin.
Sponsors
Apices Soluciones S.L.
PharmaMar
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patient who agrees to participate in the study by signing the informed consent. 2. Men and women (non-pregnant) aged ≥18 years. 3. COVID-19 infection confirmed by PCR obtained from nasopharyngeal exudate or sample from the lower respiratory tract. 4. Patients who require hospitalization for COVID-19. 5. Symptom onset at most within 10 days prior to study inclusion. 6. Men and women with reproductive capacity should agree to use highly effective contraceptive methods during their participation in the study and in the 6 months following the last administration of plitidepsin. 7. In addition, women participating in the study with reproductive ability must have a negative pregnancy test at enrollment.
Exclusion criteria
1. Patients participating in some other clinical trial for COVID-19 infection. 2. Patients who are receiving treatment with antivirals, interleukin 6 receptor inhibitors or immunomodulatory drugs for COVID-19. 3. Patients who are receiving treatment with chloroquine and derivatives. 4. Evidence of multi-organ failure. 5. Patients who require support with mechanical ventilation (invasive or non-invasive) at the time of inclusion. 6. D-dimer\> 4 x UNL. 7. Hb \<9 g / dL. 8. Neutrophils \<1000 / mm3. 9. Platelets \<100,000 / mm3. 10. Lymphopenia \<800 / μL. 11. GOT / GPT\> 3 X UNL. 12. Bilirubin\> 1 X UNL. 13. CPK\> 2.5 X UNL. 14. Creatinine clearance \<30ml / min. 15. Troponin elevation\> 1.5 x ULN. 16. Clinically relevant heart disease (NYHA\> 2). 17. Clinically relevant arrhythmia or previous history / presence of prolonged QT-QTc ≥ 450 ms. 18. Pre-existing neuropathies of any type ≥ grade 2. 19. Hypersensitivity to the active substance or to any of its excipients (macrogol glycerol ricinoleate and ethanol). 20. Patients who require or are being treated with potent CYP3A4 inhibitors and inducers. 21. Patients who for any reason should not be included in the study according to the evaluation of the research team.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With ECG Abnormalities. | At days 2, 3, 4, 5, 6, 7, 15 and 31 | Percentage of patients with ECG abnormalities. |
| Frequency of Occurrence of Neurotoxicity ≥ Grade 3 | At days 3, 7, 15 and 31 | Percentage of patients with Neurotoxicity ≥ grade 3 according to NCI-CTCAE v5.0 criteria. |
| Frequency of Occurrence of QT-QTc Interval Extension ≥ Grade 3 | At days 3, 7, 15 and 31 | Percentage of patients with QT-QTc interval extension ≥ grade 3 according to NCI-CTCAE v5.0 criteria. |
| Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | At days 3, 7, 15 and 31. | Percentage of patients with Other adverse events ≥ grade 3 according to NCI-CTCAE v5.0 criteria. |
| Percentage of Patients in Whom Treatment Cannot be Completed. | At 3 days from the first dose of study treatment | Percentage of patients in whom treatment cannot be completed and the reasons. |
| Percentage of Patients With Adverse Events. | At days 3, 7, 15 and 31 | Percentage of patients with adverse events. |
| Percentage of Patients With Serious Adverse Events. | At days 3, 7, 15 and 31 | Percentage of patients with serious adverse events. |
| Frequency of Occurrence of Neutropenia ≥ Grade 3 | At days 3, 7, 15 and 31 | Percentage of patients with Neutropenia ≥ grade 3 according to NCI-CTCAE v5.0 criteria. |
| Frequency of Occurrence of Thrombocytopenia ≥ Grade 3 | At days 3, 7, 15 and 31 | Percentage of patients with Thrombocytopenia ≥ grade 3 according to NCI-CTCAE v5.0 criteria. |
| Frequency of Occurrence of Anemia ≥ Grade 3 | At days 3, 7, 15 and 31 | Percentage of patients with Anemia ≥ grade 3 according to NCI-CTCAE v5.0 criteria. |
| Frequency of Occurrence of Lymphopenia ≥ Grade 3 | At days 3, 7, 15 and 31 | Percentage of patients with Lymphopenia ≥ grade 3 according to NCI-CTCAE v5.0 criteria. |
| Frequency of Occurrence of CPK Increase ≥ Grade 3 | At days 3, 7, 15 and 31 | Percentage of patients with CPK increase ≥ grade 3 according to NCI-CTCAE v5.0 criteria. |
| Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | At days 3, 7, 15 and 31 | Percentage of patients with Increase ALT and / or AST ≥ grade 3 according to NCI-CTCAE v5.0 criteria. |
| Frequency of Occurrence of Increase Total Bilirubin or Direct Bilirubin ≥ Grade 3 | At days 3, 7, 15 and 31 | Percentage of patients with Increase total bilirubin or direct bilirubin ≥ grade 3 according to NCI-CTCAE v5.0 criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Negative PCR Test for COVID-19 | Up to 31 days + 3 days for window period | Time from inclusion/randomization to date of negative PCR test for COVID-19 |
| Mortality | At days 7, 15 and 31 | Percentage of patients who die during the study |
| Percentage of Patients Requiring Invasive Mechanical Ventilation and / or ICU Admission | At days 7, 15 and 31 | Percentage of patients requiring invasive mechanical ventilation and / or ICU admission |
| Percentage of Patients Requiring Non-invasive Mechanical Ventilation | At days 7, 15 and 31 | Percentage of patients requiring non-invasive mechanical ventilation |
| Percentage of Patients Requiring Oxygen Therapy | At days 7, 15 and 31 | Percentage of patients requiring oxygen therapy |
| Change in the Viral Load of SARS-CoV-2 | At days 4, 7, 15 and 31 | Median change in the viral load of SARS-CoV-2 from baseline. |
Countries
Spain
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Experimental 1 Plitidepsin 1.5 mg / day x 3 consecutive days
Plitidepsin 1.5 mg/day: Plitidepsin 1.5 mg/day will be IV infused through a pump device over 1 hour and 30 minutes, 3 consecutive days. | 15 |
| Experimental 2 Plitidepsin 2.0 mg / day x 3 consecutive days
Plitidepsin 2.0 mg/day: Plitidepsin 2.0 mg/day will be IV infused through a pump device over 1 hour and 30 minutes, 3 consecutive days. | 15 |
| Experimental 3 Plitidepsin 2.5 mg / day x 3 consecutive days
Plitidepsin 2.5 mg/day: Plitidepsin 2.5 mg/day will be IV infused through a pump device over 1 hour and 30 minutes, 3 consecutive days. | 15 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Death | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Experimental 2 | Total | Experimental 1 | Experimental 3 |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 9 Participants | 3 Participants | 4 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 36 Participants | 12 Participants | 11 Participants |
| Age, Continuous | 49 years | 52 years | 51 years | 53 years |
| Alanine aminotransferase | 0.8 x Upper Limit of Normal (ULN) | 0.8 x Upper Limit of Normal (ULN) | 0.9 x Upper Limit of Normal (ULN) | 0.7 x Upper Limit of Normal (ULN) |
| Aspartate aminotransferase | 0.9 x Upper Limit of Normal (ULN) | 0.8 x Upper Limit of Normal (ULN) | 0.8 x Upper Limit of Normal (ULN) | 0.7 x Upper Limit of Normal (ULN) |
| Body temperature | 37.0 Degrees Celsius | 36.5 Degrees Celsius | 36.5 Degrees Celsius | 36.2 Degrees Celsius |
| Chest x-rays Abnormal | 13 Participants | 41 Participants | 15 Participants | 13 Participants |
| Chest x-rays Bilateral pneumonia | 10 Participants | 32 Participants | 11 Participants | 11 Participants |
| Clinical status at randomization Mild COVID-19 infection | 3 Participants | 6 Participants | 2 Participants | 1 Participants |
| Clinical status at randomization Moderate COVID-19 infection | 7 Participants | 23 Participants | 8 Participants | 8 Participants |
| Clinical status at randomization Severe COVID-19 infection | 5 Participants | 16 Participants | 5 Participants | 6 Participants |
| Comorbidities Asthma | 0 Participants | 5 Participants | 2 Participants | 3 Participants |
| Comorbidities Cardiac disease | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Comorbidities Diabetes | 5 Participants | 8 Participants | 1 Participants | 2 Participants |
| Comorbidities Hypertension | 2 Participants | 9 Participants | 2 Participants | 5 Participants |
| Comorbidities Kidney disease | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Comorbidities Lung disease (COPD) | 1 Participants | 3 Participants | 1 Participants | 1 Participants |
| Comorbidities Obesity | 5 Participants | 10 Participants | 1 Participants | 4 Participants |
| C-reactive protein | 67.2 mg/L | 32.7 mg/L | 17.7 mg/L | 32.6 mg/L |
| Creatine phosphokinase | 0.3 x Upper Limit of Normal (ULN) | 0.4 x Upper Limit of Normal (ULN) | 0.4 x Upper Limit of Normal (ULN) | 0.4 x Upper Limit of Normal (ULN) |
| D-dimer | 463 ng/mL | 405 ng/mL | 330 ng/mL | 415 ng/mL |
| Diastolic blood pressure | 71 mmHg | 72 mmHg | 69 mmHg | 78 mmHg |
| Ferritin | 597 ng/ml | 412 ng/ml | 408 ng/ml | 363 ng/ml |
| Heart rate | 78 Bpm | 82 Bpm | 84 Bpm | 82 Bpm |
| Lactate dehydrogenase | 1.0 x Upper Limit of Normal (ULN) | 1.0 x Upper Limit of Normal (ULN) | 1.0 x Upper Limit of Normal (ULN) | 1.2 x Upper Limit of Normal (ULN) |
| Lymphocytes | 1.1 10^9 cells/liter | 1.0 10^9 cells/liter | 0.9 10^9 cells/liter | 1.1 10^9 cells/liter |
| Number of comorbidities None | 2 Participants | 9 Participants | 5 Participants | 2 Participants |
| Number of comorbidities One | 7 Participants | 15 Participants | 2 Participants | 6 Participants |
| Number of comorbidities Two or more | 6 Participants | 21 Participants | 8 Participants | 7 Participants |
| On supplementary O2 | 8 Participants | 23 Participants | 6 Participants | 9 Participants |
| Oxygen saturation at room air | 95 Percentage | 95.5 Percentage | 95 Percentage | 96.5 Percentage |
| PaO2/FiO2 | 352 Ratio | 350 Ratio | 358 Ratio | 343 Ratio |
| Platelet count | 168 10^9 cells/liter | 183 10^9 cells/liter | 183 10^9 cells/liter | 244 10^9 cells/liter |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 15 Participants | 45 Participants | 15 Participants | 15 Participants |
| Region of Enrollment Spain | 15 participants | 45 participants | 15 participants | 15 participants |
| Respiratory rate | 18 Bpm | 17 Bpm | 17 Bpm | 16.5 Bpm |
| Serum creatinine | 0.8 mg/dL | 0.8 mg/dL | 0.8 mg/dL | 0.8 mg/dL |
| Sex: Female, Male Female | 4 Participants | 15 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 11 Participants | 30 Participants | 11 Participants | 8 Participants |
| Systolic blood pressure | 115 mmHg | 119 mmHg | 113 mmHg | 124 mmHg |
| Viral load | 6.2 Log10 copies/mL | 6.1 Log10 copies/mL | 6.3 Log10 copies/mL | 5.7 Log10 copies/mL |
| White Blood Cells (WBC) | 5.4 10^9 cells/liter | 5.5 10^9 cells/liter | 4.4 10^9 cells/liter | 7.1 10^9 cells/liter |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 15 | 0 / 15 | 1 / 15 | 2 / 45 |
| other Total, other adverse events | 15 / 15 | 14 / 15 | 15 / 15 | 44 / 45 |
| serious Total, serious adverse events | 6 / 15 | 1 / 15 | 3 / 15 | 10 / 45 |
Outcome results
Primary
Frequency of Occurrence of Anemia ≥ Grade 3
Percentage of patients with Anemia ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time frame: At days 3, 7, 15 and 31
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental 1 | Frequency of Occurrence of Anemia ≥ Grade 3 | Day 7 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Anemia ≥ Grade 3 | Day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Anemia ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Anemia ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Anemia ≥ Grade 3 | Day 3 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Anemia ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Anemia ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Anemia ≥ Grade 3 | Day 7 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Anemia ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Anemia ≥ Grade 3 | Day 7 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Anemia ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Anemia ≥ Grade 3 | Day 3 | 0 Participants |
| Total | Frequency of Occurrence of Anemia ≥ Grade 3 | Day 31 | 0 Participants |
| Total | Frequency of Occurrence of Anemia ≥ Grade 3 | Day 15 | 0 Participants |
| Total | Frequency of Occurrence of Anemia ≥ Grade 3 | Day 7 | 0 Participants |
| Total | Frequency of Occurrence of Anemia ≥ Grade 3 | Day 3 | 0 Participants |
Primary
Frequency of Occurrence of CPK Increase ≥ Grade 3
Percentage of patients with CPK increase ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time frame: At days 3, 7, 15 and 31
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental 1 | Frequency of Occurrence of CPK Increase ≥ Grade 3 | Day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of CPK Increase ≥ Grade 3 | Day 7 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of CPK Increase ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of CPK Increase ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of CPK Increase ≥ Grade 3 | Day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of CPK Increase ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of CPK Increase ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of CPK Increase ≥ Grade 3 | Day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of CPK Increase ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of CPK Increase ≥ Grade 3 | Day 7 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of CPK Increase ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of CPK Increase ≥ Grade 3 | Day 3 | 0 Participants |
| Total | Frequency of Occurrence of CPK Increase ≥ Grade 3 | Day 31 | 0 Participants |
| Total | Frequency of Occurrence of CPK Increase ≥ Grade 3 | Day 7 | 0 Participants |
| Total | Frequency of Occurrence of CPK Increase ≥ Grade 3 | Day 3 | 0 Participants |
| Total | Frequency of Occurrence of CPK Increase ≥ Grade 3 | Day 15 | 0 Participants |
Primary
Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3
Percentage of patients with Increase ALT and / or AST ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time frame: At days 3, 7, 15 and 31
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental 1 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | ALT increased Day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | ALT increased Day 7 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | ALT increased Day 15 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | ALT increased Day 31 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | AST increased Day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | AST increased Day 7 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | AST increased Day 15 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | AST increased Day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | AST increased Day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | AST increased Day 3 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | ALT increased Day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | AST increased Day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | AST increased Day 15 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | ALT increased Day 31 | 1 Participants |
| Experimental 2 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | ALT increased Day 15 | 1 Participants |
| Experimental 2 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | ALT increased Day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | AST increased Day 15 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | ALT increased Day 15 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | ALT increased Day 31 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | AST increased Day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | AST increased Day 7 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | AST increased Day 31 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | ALT increased Day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | ALT increased Day 7 | 0 Participants |
| Total | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | ALT increased Day 15 | 1 Participants |
| Total | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | ALT increased Day 31 | 1 Participants |
| Total | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | ALT increased Day 7 | 0 Participants |
| Total | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | ALT increased Day 3 | 0 Participants |
| Total | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | AST increased Day 3 | 0 Participants |
| Total | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | AST increased Day 31 | 0 Participants |
| Total | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | AST increased Day 15 | 0 Participants |
| Total | Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 | AST increased Day 7 | 0 Participants |
Primary
Frequency of Occurrence of Increase Total Bilirubin or Direct Bilirubin ≥ Grade 3
Percentage of patients with Increase total bilirubin or direct bilirubin ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time frame: At days 3, 7, 15 and 31
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental 1 | Frequency of Occurrence of Increase Total Bilirubin or Direct Bilirubin ≥ Grade 3 | Day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Increase Total Bilirubin or Direct Bilirubin ≥ Grade 3 | Day 7 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Increase Total Bilirubin or Direct Bilirubin ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Increase Total Bilirubin or Direct Bilirubin ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Increase Total Bilirubin or Direct Bilirubin ≥ Grade 3 | Day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Increase Total Bilirubin or Direct Bilirubin ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Increase Total Bilirubin or Direct Bilirubin ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Increase Total Bilirubin or Direct Bilirubin ≥ Grade 3 | Day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Increase Total Bilirubin or Direct Bilirubin ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Increase Total Bilirubin or Direct Bilirubin ≥ Grade 3 | Day 7 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Increase Total Bilirubin or Direct Bilirubin ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Increase Total Bilirubin or Direct Bilirubin ≥ Grade 3 | Day 3 | 0 Participants |
| Total | Frequency of Occurrence of Increase Total Bilirubin or Direct Bilirubin ≥ Grade 3 | Day 31 | 0 Participants |
| Total | Frequency of Occurrence of Increase Total Bilirubin or Direct Bilirubin ≥ Grade 3 | Day 7 | 0 Participants |
| Total | Frequency of Occurrence of Increase Total Bilirubin or Direct Bilirubin ≥ Grade 3 | Day 3 | 0 Participants |
| Total | Frequency of Occurrence of Increase Total Bilirubin or Direct Bilirubin ≥ Grade 3 | Day 15 | 0 Participants |
Primary
Frequency of Occurrence of Lymphopenia ≥ Grade 3
Percentage of patients with Lymphopenia ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time frame: At days 3, 7, 15 and 31
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental 1 | Frequency of Occurrence of Lymphopenia ≥ Grade 3 | Day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Lymphopenia ≥ Grade 3 | Day 7 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Lymphopenia ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Lymphopenia ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Lymphopenia ≥ Grade 3 | Day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Lymphopenia ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Lymphopenia ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Lymphopenia ≥ Grade 3 | Day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Lymphopenia ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Lymphopenia ≥ Grade 3 | Day 7 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Lymphopenia ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Lymphopenia ≥ Grade 3 | Day 3 | 0 Participants |
| Total | Frequency of Occurrence of Lymphopenia ≥ Grade 3 | Day 31 | 0 Participants |
| Total | Frequency of Occurrence of Lymphopenia ≥ Grade 3 | Day 7 | 0 Participants |
| Total | Frequency of Occurrence of Lymphopenia ≥ Grade 3 | Day 3 | 0 Participants |
| Total | Frequency of Occurrence of Lymphopenia ≥ Grade 3 | Day 15 | 0 Participants |
Primary
Frequency of Occurrence of Neurotoxicity ≥ Grade 3
Percentage of patients with Neurotoxicity ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time frame: At days 3, 7, 15 and 31
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental 1 | Frequency of Occurrence of Neurotoxicity ≥ Grade 3 | Day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Neurotoxicity ≥ Grade 3 | Day 7 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Neurotoxicity ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Neurotoxicity ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Neurotoxicity ≥ Grade 3 | Day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Neurotoxicity ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Neurotoxicity ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Neurotoxicity ≥ Grade 3 | Day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Neurotoxicity ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Neurotoxicity ≥ Grade 3 | Day 7 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Neurotoxicity ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Neurotoxicity ≥ Grade 3 | Day 3 | 0 Participants |
| Total | Frequency of Occurrence of Neurotoxicity ≥ Grade 3 | Day 31 | 0 Participants |
| Total | Frequency of Occurrence of Neurotoxicity ≥ Grade 3 | Day 7 | 0 Participants |
| Total | Frequency of Occurrence of Neurotoxicity ≥ Grade 3 | Day 3 | 0 Participants |
| Total | Frequency of Occurrence of Neurotoxicity ≥ Grade 3 | Day 15 | 0 Participants |
Primary
Frequency of Occurrence of Neutropenia ≥ Grade 3
Percentage of patients with Neutropenia ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time frame: At days 3, 7, 15 and 31
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental 1 | Frequency of Occurrence of Neutropenia ≥ Grade 3 | Day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Neutropenia ≥ Grade 3 | Day 7 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Neutropenia ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Neutropenia ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Neutropenia ≥ Grade 3 | Day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Neutropenia ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Neutropenia ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Neutropenia ≥ Grade 3 | Day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Neutropenia ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Neutropenia ≥ Grade 3 | Day 7 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Neutropenia ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Neutropenia ≥ Grade 3 | Day 3 | 0 Participants |
| Total | Frequency of Occurrence of Neutropenia ≥ Grade 3 | Day 31 | 0 Participants |
| Total | Frequency of Occurrence of Neutropenia ≥ Grade 3 | Day 7 | 0 Participants |
| Total | Frequency of Occurrence of Neutropenia ≥ Grade 3 | Day 3 | 0 Participants |
| Total | Frequency of Occurrence of Neutropenia ≥ Grade 3 | Day 15 | 0 Participants |
Primary
Frequency of Occurrence of Other Adverse Events ≥ Grade 3
Percentage of patients with Other adverse events ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time frame: At days 3, 7, 15 and 31.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | C-reactive protein increased day 15 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Condition aggravated day 3 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Hyperglycaemia day 31 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Urinary tract infection day 15 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Urinary tract infection day 31 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Respiratory distress day 31 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Hyperglycaemia day 15 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | C-reactive protein increased day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | C-reactive protein increased day 7 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Condition aggravated day 7 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Hyperglycaemia day 7 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | C-reactive protein increased day 31 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Hyperglycaemia day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Gamma-glutamyltransferase increased day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Leukocytosis day 15 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Gamma-glutamyltransferase increased day 7 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumomediastinum day 31 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Serum ferritin increased day 31 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Gamma-glutamyltransferase increased day 15 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Gamma-glutamyltransferase increased day 31 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Condition aggravated day 15 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Serum ferritin increased day 15 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Serum ferritin increased day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Serum ferritin increased day 7 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Condition aggravated day 31 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumomediastinum day 15 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Anaphylactic reaction day 3 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Anaphylactic reaction day 7 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Leukocytosis day 31 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumomediastinum day 7 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Anaphylactic reaction day 15 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Anaphylactic reaction day 31 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumomediastinum day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Bacteraemia day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Respiratory distress day 15 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Bacteraemia day 7 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Diarrhoea day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Acute respiratory distress syndrome day 31 | 2 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Bacteraemia day 15 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Bacteraemia day 31 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Acute respiratory distress syndrome day 15 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | COVID-19 pneumonia day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | COVID-19 pneumonia day 7 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Diarrhoea day 7 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Acute respiratory distress syndrome day 7 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | COVID-19 pneumonia day 15 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | COVID-19 pneumonia day 31 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Leukocytosis day 7 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Acute respiratory distress syndrome day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumonia day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Respiratory distress day 7 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumonia day 7 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Diarrhoea day 15 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Status epilepticus day 31 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumonia day 15 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumonia day 31 | 1 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Status epilepticus day 15 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Superinfection bacterial day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Superinfection bacterial day 7 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Diarrhoea day 31 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Status epilepticus day 7 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Superinfection bacterial day 15 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Superinfection bacterial day 31 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Leukocytosis day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Status epilepticus day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Urinary tract infection day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Respiratory distress day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Urinary tract infection day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Bacteraemia day 3 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Status epilepticus day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Acute respiratory distress syndrome day 31 | 1 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Status epilepticus day 3 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Urinary tract infection day 15 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Condition aggravated day 3 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Hyperglycaemia day 15 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Bacteraemia day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Urinary tract infection day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumonia day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Superinfection bacterial day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Urinary tract infection day 3 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | C-reactive protein increased day 3 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumomediastinum day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Hyperglycaemia day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Bacteraemia day 15 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | C-reactive protein increased day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Diarrhoea day 3 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Acute respiratory distress syndrome day 15 | 1 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Hyperglycaemia day 3 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Superinfection bacterial day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | C-reactive protein increased day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Condition aggravated day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Bacteraemia day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Respiratory distress day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Gamma-glutamyltransferase increased day 3 | 1 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumonia day 15 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Serum ferritin increased day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Diarrhoea day 15 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Gamma-glutamyltransferase increased day 7 | 1 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | COVID-19 pneumonia day 3 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Respiratory distress day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Acute respiratory distress syndrome day 7 | 1 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Gamma-glutamyltransferase increased day 15 | 2 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Urinary tract infection day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Serum ferritin increased day 15 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Status epilepticus day 15 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Gamma-glutamyltransferase increased day 31 | 2 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | COVID-19 pneumonia day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Hyperglycaemia day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumonia day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Serum ferritin increased day 3 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Condition aggravated day 15 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Serum ferritin increased day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Leukocytosis day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Leukocytosis day 15 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumomediastinum day 15 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | COVID-19 pneumonia day 15 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Condition aggravated day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Leukocytosis day 3 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Diarrhoea day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Acute respiratory distress syndrome day 3 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Anaphylactic reaction day 3 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Respiratory distress day 15 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumomediastinum day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Superinfection bacterial day 15 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Anaphylactic reaction day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | COVID-19 pneumonia day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Diarrhoea day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Superinfection bacterial day 3 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Anaphylactic reaction day 15 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Leukocytosis day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumomediastinum day 3 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Respiratory distress day 3 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Anaphylactic reaction day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | C-reactive protein increased day 15 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumonia day 3 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Status epilepticus day 7 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Gamma-glutamyltransferase increased day 15 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | C-reactive protein increased day 15 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Leukocytosis day 3 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Leukocytosis day 7 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Leukocytosis day 15 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Leukocytosis day 31 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Diarrhoea day 3 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Diarrhoea day 7 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Diarrhoea day 15 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Diarrhoea day 31 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Condition aggravated day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Condition aggravated day 7 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Condition aggravated day 15 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Condition aggravated day 31 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Anaphylactic reaction day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Anaphylactic reaction day 7 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Anaphylactic reaction day 15 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Anaphylactic reaction day 31 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Bacteraemia day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Bacteraemia day 7 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Bacteraemia day 15 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Bacteraemia day 31 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | COVID-19 pneumonia day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | COVID-19 pneumonia day 7 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | COVID-19 pneumonia day 15 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | COVID-19 pneumonia day 31 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumonia day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumonia day 7 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumonia day 15 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumonia day 31 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Superinfection bacterial day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Superinfection bacterial day 7 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Superinfection bacterial day 15 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Superinfection bacterial day 31 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Urinary tract infection day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Urinary tract infection day 7 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Urinary tract infection day 15 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Urinary tract infection day 31 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | C-reactive protein increased day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | C-reactive protein increased day 7 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | C-reactive protein increased day 31 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Gamma-glutamyltransferase increased day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Gamma-glutamyltransferase increased day 7 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Gamma-glutamyltransferase increased day 31 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Serum ferritin increased day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Serum ferritin increased day 7 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Serum ferritin increased day 15 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Serum ferritin increased day 31 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Hyperglycaemia day 3 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Hyperglycaemia day 7 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Hyperglycaemia day 15 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Hyperglycaemia day 31 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Status epilepticus day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Status epilepticus day 7 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Status epilepticus day 15 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Status epilepticus day 31 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Acute respiratory distress syndrome day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Acute respiratory distress syndrome day 7 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Acute respiratory distress syndrome day 15 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Acute respiratory distress syndrome day 31 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumomediastinum day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumomediastinum day 7 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumomediastinum day 15 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumomediastinum day 31 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Respiratory distress day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Respiratory distress day 7 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Respiratory distress day 15 | 1 Participants |
| Experimental 3 | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Respiratory distress day 31 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Urinary tract infection day 7 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Urinary tract infection day 3 | 0 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumomediastinum day 31 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Hyperglycaemia day 31 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Superinfection bacterial day 31 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Superinfection bacterial day 15 | 0 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Diarrhoea day 31 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Status epilepticus day 3 | 0 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Superinfection bacterial day 7 | 0 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Superinfection bacterial day 3 | 0 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Diarrhoea day 15 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Status epilepticus day 7 | 0 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumonia day 31 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumonia day 15 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Leukocytosis day 7 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Status epilepticus day 15 | 0 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumonia day 7 | 0 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumonia day 3 | 0 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Respiratory distress day 3 | 0 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Status epilepticus day 31 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | COVID-19 pneumonia day 31 | 2 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | COVID-19 pneumonia day 15 | 2 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Diarrhoea day 7 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Acute respiratory distress syndrome day 3 | 0 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | COVID-19 pneumonia day 7 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | COVID-19 pneumonia day 3 | 0 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Diarrhoea day 3 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Acute respiratory distress syndrome day 7 | 2 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Bacteraemia day 31 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Bacteraemia day 15 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Leukocytosis day 3 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Acute respiratory distress syndrome day 15 | 3 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Bacteraemia day 7 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Bacteraemia day 3 | 0 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Respiratory distress day 7 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Acute respiratory distress syndrome day 31 | 4 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Anaphylactic reaction day 31 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Anaphylactic reaction day 15 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Leukocytosis day 31 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumomediastinum day 3 | 0 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Anaphylactic reaction day 7 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Anaphylactic reaction day 3 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Leukocytosis day 15 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumomediastinum day 7 | 0 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Condition aggravated day 31 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Serum ferritin increased day 3 | 0 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Condition aggravated day 15 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Serum ferritin increased day 7 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Gamma-glutamyltransferase increased day 31 | 3 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Gamma-glutamyltransferase increased day 15 | 3 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Respiratory distress day 31 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Serum ferritin increased day 15 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Gamma-glutamyltransferase increased day 7 | 2 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Gamma-glutamyltransferase increased day 3 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Pneumomediastinum day 15 | 0 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Serum ferritin increased day 31 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | C-reactive protein increased day 31 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | C-reactive protein increased day 15 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Condition aggravated day 7 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Hyperglycaemia day 3 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | C-reactive protein increased day 7 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | C-reactive protein increased day 3 | 0 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Condition aggravated day 3 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Hyperglycaemia day 7 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Urinary tract infection day 31 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Urinary tract infection day 15 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Respiratory distress day 15 | 1 Participants |
| Total | Frequency of Occurrence of Other Adverse Events ≥ Grade 3 | Hyperglycaemia day 15 | 1 Participants |
Primary
Frequency of Occurrence of QT-QTc Interval Extension ≥ Grade 3
Percentage of patients with QT-QTc interval extension ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time frame: At days 3, 7, 15 and 31
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental 1 | Frequency of Occurrence of QT-QTc Interval Extension ≥ Grade 3 | Day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of QT-QTc Interval Extension ≥ Grade 3 | Day 7 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of QT-QTc Interval Extension ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of QT-QTc Interval Extension ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of QT-QTc Interval Extension ≥ Grade 3 | Day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of QT-QTc Interval Extension ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of QT-QTc Interval Extension ≥ Grade 3 | Day 3 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of QT-QTc Interval Extension ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of QT-QTc Interval Extension ≥ Grade 3 | Day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of QT-QTc Interval Extension ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of QT-QTc Interval Extension ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of QT-QTc Interval Extension ≥ Grade 3 | Day 7 | 0 Participants |
| Total | Frequency of Occurrence of QT-QTc Interval Extension ≥ Grade 3 | Day 31 | 0 Participants |
| Total | Frequency of Occurrence of QT-QTc Interval Extension ≥ Grade 3 | Day 3 | 0 Participants |
| Total | Frequency of Occurrence of QT-QTc Interval Extension ≥ Grade 3 | Day 7 | 0 Participants |
| Total | Frequency of Occurrence of QT-QTc Interval Extension ≥ Grade 3 | Day 15 | 0 Participants |
Primary
Frequency of Occurrence of Thrombocytopenia ≥ Grade 3
Percentage of patients with Thrombocytopenia ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time frame: At days 3, 7, 15 and 31
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental 1 | Frequency of Occurrence of Thrombocytopenia ≥ Grade 3 | Day 3 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Thrombocytopenia ≥ Grade 3 | Day 7 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Thrombocytopenia ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 1 | Frequency of Occurrence of Thrombocytopenia ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Thrombocytopenia ≥ Grade 3 | Day 7 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Thrombocytopenia ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Thrombocytopenia ≥ Grade 3 | Day 3 | 0 Participants |
| Experimental 2 | Frequency of Occurrence of Thrombocytopenia ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Thrombocytopenia ≥ Grade 3 | Day 3 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Thrombocytopenia ≥ Grade 3 | Day 31 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Thrombocytopenia ≥ Grade 3 | Day 15 | 0 Participants |
| Experimental 3 | Frequency of Occurrence of Thrombocytopenia ≥ Grade 3 | Day 7 | 0 Participants |
| Total | Frequency of Occurrence of Thrombocytopenia ≥ Grade 3 | Day 31 | 0 Participants |
| Total | Frequency of Occurrence of Thrombocytopenia ≥ Grade 3 | Day 3 | 0 Participants |
| Total | Frequency of Occurrence of Thrombocytopenia ≥ Grade 3 | Day 7 | 0 Participants |
| Total | Frequency of Occurrence of Thrombocytopenia ≥ Grade 3 | Day 15 | 0 Participants |
Primary
Percentage of Patients in Whom Treatment Cannot be Completed.
Percentage of patients in whom treatment cannot be completed and the reasons.
Time frame: At 3 days from the first dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Experimental 1 | Percentage of Patients in Whom Treatment Cannot be Completed. | 1 Participants |
| Experimental 2 | Percentage of Patients in Whom Treatment Cannot be Completed. | 0 Participants |
| Experimental 3 | Percentage of Patients in Whom Treatment Cannot be Completed. | 0 Participants |
| Total | Percentage of Patients in Whom Treatment Cannot be Completed. | 1 Participants |
Primary
Percentage of Patients With Adverse Events.
Percentage of patients with adverse events.
Time frame: At days 3, 7, 15 and 31
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental 1 | Percentage of Patients With Adverse Events. | Day 3 | 14 Participants |
| Experimental 1 | Percentage of Patients With Adverse Events. | Day 7 | 15 Participants |
| Experimental 1 | Percentage of Patients With Adverse Events. | Day 15 | 15 Participants |
| Experimental 1 | Percentage of Patients With Adverse Events. | Day 31 | 15 Participants |
| Experimental 2 | Percentage of Patients With Adverse Events. | Day 7 | 14 Participants |
| Experimental 2 | Percentage of Patients With Adverse Events. | Day 15 | 14 Participants |
| Experimental 2 | Percentage of Patients With Adverse Events. | Day 31 | 14 Participants |
| Experimental 2 | Percentage of Patients With Adverse Events. | Day 3 | 11 Participants |
| Experimental 3 | Percentage of Patients With Adverse Events. | Day 15 | 15 Participants |
| Experimental 3 | Percentage of Patients With Adverse Events. | Day 7 | 15 Participants |
| Experimental 3 | Percentage of Patients With Adverse Events. | Day 31 | 15 Participants |
| Experimental 3 | Percentage of Patients With Adverse Events. | Day 3 | 13 Participants |
| Total | Percentage of Patients With Adverse Events. | Day 31 | 44 Participants |
| Total | Percentage of Patients With Adverse Events. | Day 7 | 44 Participants |
| Total | Percentage of Patients With Adverse Events. | Day 3 | 38 Participants |
| Total | Percentage of Patients With Adverse Events. | Day 15 | 44 Participants |
Primary
Percentage of Patients With ECG Abnormalities.
Percentage of patients with ECG abnormalities.
Time frame: At days 2, 3, 4, 5, 6, 7, 15 and 31
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental 1 | Percentage of Patients With ECG Abnormalities. | Day 2 | 2 Participants |
| Experimental 1 | Percentage of Patients With ECG Abnormalities. | Day 3 | 4 Participants |
| Experimental 1 | Percentage of Patients With ECG Abnormalities. | Day 4 | 3 Participants |
| Experimental 1 | Percentage of Patients With ECG Abnormalities. | Day 5 | 3 Participants |
| Experimental 1 | Percentage of Patients With ECG Abnormalities. | Day 6 | 4 Participants |
| Experimental 1 | Percentage of Patients With ECG Abnormalities. | Day 7 | 1 Participants |
| Experimental 1 | Percentage of Patients With ECG Abnormalities. | Day 15 | 2 Participants |
| Experimental 1 | Percentage of Patients With ECG Abnormalities. | Day 31 | 2 Participants |
| Experimental 2 | Percentage of Patients With ECG Abnormalities. | Day 7 | 1 Participants |
| Experimental 2 | Percentage of Patients With ECG Abnormalities. | Day 6 | 1 Participants |
| Experimental 2 | Percentage of Patients With ECG Abnormalities. | Day 3 | 2 Participants |
| Experimental 2 | Percentage of Patients With ECG Abnormalities. | Day 31 | 0 Participants |
| Experimental 2 | Percentage of Patients With ECG Abnormalities. | Day 15 | 2 Participants |
| Experimental 2 | Percentage of Patients With ECG Abnormalities. | Day 5 | 1 Participants |
| Experimental 2 | Percentage of Patients With ECG Abnormalities. | Day 4 | 1 Participants |
| Experimental 2 | Percentage of Patients With ECG Abnormalities. | Day 2 | 3 Participants |
| Experimental 3 | Percentage of Patients With ECG Abnormalities. | Day 15 | 2 Participants |
| Experimental 3 | Percentage of Patients With ECG Abnormalities. | Day 4 | 1 Participants |
| Experimental 3 | Percentage of Patients With ECG Abnormalities. | Day 5 | 2 Participants |
| Experimental 3 | Percentage of Patients With ECG Abnormalities. | Day 6 | 2 Participants |
| Experimental 3 | Percentage of Patients With ECG Abnormalities. | Day 7 | 3 Participants |
| Experimental 3 | Percentage of Patients With ECG Abnormalities. | Day 31 | 1 Participants |
| Experimental 3 | Percentage of Patients With ECG Abnormalities. | Day 2 | 3 Participants |
| Experimental 3 | Percentage of Patients With ECG Abnormalities. | Day 3 | 2 Participants |
| Total | Percentage of Patients With ECG Abnormalities. | Day 4 | 5 Participants |
| Total | Percentage of Patients With ECG Abnormalities. | Day 5 | 6 Participants |
| Total | Percentage of Patients With ECG Abnormalities. | Day 3 | 8 Participants |
| Total | Percentage of Patients With ECG Abnormalities. | Day 2 | 8 Participants |
| Total | Percentage of Patients With ECG Abnormalities. | Day 6 | 7 Participants |
| Total | Percentage of Patients With ECG Abnormalities. | Day 31 | 3 Participants |
| Total | Percentage of Patients With ECG Abnormalities. | Day 15 | 6 Participants |
| Total | Percentage of Patients With ECG Abnormalities. | Day 7 | 5 Participants |
Primary
Percentage of Patients With Serious Adverse Events.
Percentage of patients with serious adverse events.
Time frame: At days 3, 7, 15 and 31
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental 1 | Percentage of Patients With Serious Adverse Events. | Day 3 | 1 Participants |
| Experimental 1 | Percentage of Patients With Serious Adverse Events. | Day 7 | 4 Participants |
| Experimental 1 | Percentage of Patients With Serious Adverse Events. | Day 15 | 4 Participants |
| Experimental 1 | Percentage of Patients With Serious Adverse Events. | Day 31 | 6 Participants |
| Experimental 2 | Percentage of Patients With Serious Adverse Events. | Day 7 | 1 Participants |
| Experimental 2 | Percentage of Patients With Serious Adverse Events. | Day 15 | 1 Participants |
| Experimental 2 | Percentage of Patients With Serious Adverse Events. | Day 31 | 1 Participants |
| Experimental 2 | Percentage of Patients With Serious Adverse Events. | Day 3 | 0 Participants |
| Experimental 3 | Percentage of Patients With Serious Adverse Events. | Day 15 | 2 Participants |
| Experimental 3 | Percentage of Patients With Serious Adverse Events. | Day 7 | 0 Participants |
| Experimental 3 | Percentage of Patients With Serious Adverse Events. | Day 31 | 3 Participants |
| Experimental 3 | Percentage of Patients With Serious Adverse Events. | Day 3 | 0 Participants |
| Total | Percentage of Patients With Serious Adverse Events. | Day 31 | 10 Participants |
| Total | Percentage of Patients With Serious Adverse Events. | Day 7 | 5 Participants |
| Total | Percentage of Patients With Serious Adverse Events. | Day 3 | 1 Participants |
| Total | Percentage of Patients With Serious Adverse Events. | Day 15 | 7 Participants |
Secondary
Change in the Viral Load of SARS-CoV-2
Median change in the viral load of SARS-CoV-2 from baseline.
Time frame: At days 4, 7, 15 and 31
Population: One patient dosed at 1.5 mg experienced an anaphylactic reaction during the first plitidepsin infusion and discontinued study treatment, so was not considered evaluable for efficacy.
| Arm | Measure | Group | Value (MEDIAN) | Dispersion |
|---|---|---|---|---|
| Experimental 1 | Change in the Viral Load of SARS-CoV-2 | Day 4 | -1.23 Log10 copies/mL | Standard Deviation 1.3 |
| Experimental 1 | Change in the Viral Load of SARS-CoV-2 | Day 7 | -2.55 Log10 copies/mL | Standard Deviation 1.65 |
| Experimental 1 | Change in the Viral Load of SARS-CoV-2 | Day 15 | -4.22 Log10 copies/mL | Standard Deviation 2.58 |
| Experimental 1 | Change in the Viral Load of SARS-CoV-2 | Day 31 | -4.70 Log10 copies/mL | Standard Deviation 1.74 |
| Experimental 2 | Change in the Viral Load of SARS-CoV-2 | Day 7 | -2.26 Log10 copies/mL | Standard Deviation 1.68 |
| Experimental 2 | Change in the Viral Load of SARS-CoV-2 | Day 15 | -2.70 Log10 copies/mL | Standard Deviation 2.23 |
| Experimental 2 | Change in the Viral Load of SARS-CoV-2 | Day 31 | -3.53 Log10 copies/mL | Standard Deviation 2.07 |
| Experimental 2 | Change in the Viral Load of SARS-CoV-2 | Day 4 | -1.49 Log10 copies/mL | Standard Deviation 1.42 |
| Experimental 3 | Change in the Viral Load of SARS-CoV-2 | Day 15 | -2.92 Log10 copies/mL | Standard Deviation 1.91 |
| Experimental 3 | Change in the Viral Load of SARS-CoV-2 | Day 7 | -2.25 Log10 copies/mL | Standard Deviation 1.61 |
| Experimental 3 | Change in the Viral Load of SARS-CoV-2 | Day 31 | -3.49 Log10 copies/mL | Standard Deviation 2.94 |
| Experimental 3 | Change in the Viral Load of SARS-CoV-2 | Day 4 | -1.32 Log10 copies/mL | Standard Deviation 1.9 |
| Total | Change in the Viral Load of SARS-CoV-2 | Day 31 | -3.85 Log10 copies/mL | Standard Deviation 2.35 |
| Total | Change in the Viral Load of SARS-CoV-2 | Day 7 | -2.35 Log10 copies/mL | Standard Deviation 1.61 |
| Total | Change in the Viral Load of SARS-CoV-2 | Day 4 | -1.35 Log10 copies/mL | Standard Deviation 1.54 |
| Total | Change in the Viral Load of SARS-CoV-2 | Day 15 | -3.25 Log10 copies/mL | Standard Deviation 2.29 |
Secondary
Mortality
Percentage of patients who die during the study
Time frame: At days 7, 15 and 31
Population: One patient dosed at 1.5 mg experienced an anaphylactic reaction during the first plitidepsin infusion and discontinued study treatment, so was not considered evaluable for efficacy.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental 1 | Mortality | Day 31 | 1 Participants |
| Experimental 1 | Mortality | Day 15 | 0 Participants |
| Experimental 1 | Mortality | Day 7 | 0 Participants |
| Experimental 2 | Mortality | Day 31 | 0 Participants |
| Experimental 2 | Mortality | Day 7 | 0 Participants |
| Experimental 2 | Mortality | Day 15 | 0 Participants |
| Experimental 3 | Mortality | Day 7 | 0 Participants |
| Experimental 3 | Mortality | Day 15 | 0 Participants |
| Experimental 3 | Mortality | Day 31 | 1 Participants |
| Total | Mortality | Day 15 | 0 Participants |
| Total | Mortality | Day 7 | 0 Participants |
| Total | Mortality | Day 31 | 2 Participants |
Secondary
Percentage of Patients Requiring Invasive Mechanical Ventilation and / or ICU Admission
Percentage of patients requiring invasive mechanical ventilation and / or ICU admission
Time frame: At days 7, 15 and 31
Population: One patient dosed at 1.5 mg experienced an anaphylactic reaction during the first plitidepsin infusion and discontinued study treatment, so was not considered evaluable for efficacy. Cumulative results.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental 1 | Percentage of Patients Requiring Invasive Mechanical Ventilation and / or ICU Admission | Day 7 | 2 Participants |
| Experimental 1 | Percentage of Patients Requiring Invasive Mechanical Ventilation and / or ICU Admission | Day 31 | 2 Participants |
| Experimental 1 | Percentage of Patients Requiring Invasive Mechanical Ventilation and / or ICU Admission | Day 15 | 2 Participants |
| Experimental 2 | Percentage of Patients Requiring Invasive Mechanical Ventilation and / or ICU Admission | Day 7 | 1 Participants |
| Experimental 2 | Percentage of Patients Requiring Invasive Mechanical Ventilation and / or ICU Admission | Day 31 | 1 Participants |
| Experimental 2 | Percentage of Patients Requiring Invasive Mechanical Ventilation and / or ICU Admission | Day 15 | 1 Participants |
| Experimental 3 | Percentage of Patients Requiring Invasive Mechanical Ventilation and / or ICU Admission | Day 15 | 3 Participants |
| Experimental 3 | Percentage of Patients Requiring Invasive Mechanical Ventilation and / or ICU Admission | Day 7 | 2 Participants |
| Experimental 3 | Percentage of Patients Requiring Invasive Mechanical Ventilation and / or ICU Admission | Day 31 | 3 Participants |
| Total | Percentage of Patients Requiring Invasive Mechanical Ventilation and / or ICU Admission | Day 7 | 5 Participants |
| Total | Percentage of Patients Requiring Invasive Mechanical Ventilation and / or ICU Admission | Day 31 | 6 Participants |
| Total | Percentage of Patients Requiring Invasive Mechanical Ventilation and / or ICU Admission | Day 15 | 6 Participants |
Secondary
Percentage of Patients Requiring Non-invasive Mechanical Ventilation
Percentage of patients requiring non-invasive mechanical ventilation
Time frame: At days 7, 15 and 31
Population: One patient dosed at 1.5 mg experienced an anaphylactic reaction during the first plitidepsin infusion and discontinued study treatment, so was not considered evaluable for efficacy. Cumulative results.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental 1 | Percentage of Patients Requiring Non-invasive Mechanical Ventilation | Day 7 | 4 Participants |
| Experimental 1 | Percentage of Patients Requiring Non-invasive Mechanical Ventilation | Day 31 | 5 Participants |
| Experimental 1 | Percentage of Patients Requiring Non-invasive Mechanical Ventilation | Day 15 | 5 Participants |
| Experimental 2 | Percentage of Patients Requiring Non-invasive Mechanical Ventilation | Day 7 | 0 Participants |
| Experimental 2 | Percentage of Patients Requiring Non-invasive Mechanical Ventilation | Day 31 | 1 Participants |
| Experimental 2 | Percentage of Patients Requiring Non-invasive Mechanical Ventilation | Day 15 | 0 Participants |
| Experimental 3 | Percentage of Patients Requiring Non-invasive Mechanical Ventilation | Day 15 | 2 Participants |
| Experimental 3 | Percentage of Patients Requiring Non-invasive Mechanical Ventilation | Day 7 | 1 Participants |
| Experimental 3 | Percentage of Patients Requiring Non-invasive Mechanical Ventilation | Day 31 | 2 Participants |
| Total | Percentage of Patients Requiring Non-invasive Mechanical Ventilation | Day 7 | 5 Participants |
| Total | Percentage of Patients Requiring Non-invasive Mechanical Ventilation | Day 31 | 8 Participants |
| Total | Percentage of Patients Requiring Non-invasive Mechanical Ventilation | Day 15 | 7 Participants |
Secondary
Percentage of Patients Requiring Oxygen Therapy
Percentage of patients requiring oxygen therapy
Time frame: At days 7, 15 and 31
Population: One patient dosed at 1.5 mg experienced an anaphylactic reaction during the first plitidepsin infusion and discontinued study treatment, so was not considered evaluable for efficacy. Cumulative results.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Experimental 1 | Percentage of Patients Requiring Oxygen Therapy | Day 31 | 12 Participants |
| Experimental 1 | Percentage of Patients Requiring Oxygen Therapy | Day 7 | 12 Participants |
| Experimental 1 | Percentage of Patients Requiring Oxygen Therapy | Day 15 | 12 Participants |
| Experimental 2 | Percentage of Patients Requiring Oxygen Therapy | Day 15 | 12 Participants |
| Experimental 2 | Percentage of Patients Requiring Oxygen Therapy | Day 7 | 12 Participants |
| Experimental 2 | Percentage of Patients Requiring Oxygen Therapy | Day 31 | 12 Participants |
| Experimental 3 | Percentage of Patients Requiring Oxygen Therapy | Day 31 | 11 Participants |
| Experimental 3 | Percentage of Patients Requiring Oxygen Therapy | Day 7 | 11 Participants |
| Experimental 3 | Percentage of Patients Requiring Oxygen Therapy | Day 15 | 11 Participants |
| Total | Percentage of Patients Requiring Oxygen Therapy | Day 15 | 35 Participants |
| Total | Percentage of Patients Requiring Oxygen Therapy | Day 7 | 35 Participants |
| Total | Percentage of Patients Requiring Oxygen Therapy | Day 31 | 35 Participants |
Secondary
Time to Negative PCR Test for COVID-19
Time from inclusion/randomization to date of negative PCR test for COVID-19
Time frame: Up to 31 days + 3 days for window period
Population: One patient dosed at 1.5 mg experienced an anaphylactic reaction during the first plitidepsin infusion and discontinued study treatment, so was not considered evaluable for efficacy.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Experimental 1 | Time to Negative PCR Test for COVID-19 | 11 Days |
| Experimental 2 | Time to Negative PCR Test for COVID-19 | 14 Days |
| Experimental 3 | Time to Negative PCR Test for COVID-19 | 14 Days |
| Total | Time to Negative PCR Test for COVID-19 | 13 Days |