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| ID | Type | Description | Link |
|---|---|---|---|
| 2020-001993-31 | EudraCT Number |
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| Name | Class |
|---|---|
| Apices Soluciones S.L. | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Experimental 1 | Experimental | Plitidepsin 1.5 mg / day x 3 consecutive days |
|
| Experimental 2 | Experimental | Plitidepsin 2.0 mg / day x 3 consecutive days |
|
| Experimental 3 | Experimental | Plitidepsin 2.5 mg / day x 3 consecutive days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Plitidepsin 1.5 mg/day | Drug | 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:
|
| Measure | Description | Time Frame |
|---|---|---|
| Frequency of Occurrence of Neutropenia ≥ Grade 3 | Percentage of patients with Neutropenia ≥ grade 3 according to NCI-CTCAE v5.0 criteria. | At days 3, 7, 15 and 31 |
| Frequency of Occurrence of Thrombocytopenia ≥ Grade 3 | Percentage of patients with Thrombocytopenia ≥ grade 3 according to NCI-CTCAE v5.0 criteria. | At days 3, 7, 15 and 31 |
| Frequency of Occurrence of Anemia ≥ Grade 3 | Percentage of patients with Anemia ≥ grade 3 according to NCI-CTCAE v5.0 criteria. | At days 3, 7, 15 and 31 |
| Frequency of Occurrence of Lymphopenia ≥ Grade 3 | Percentage of patients with Lymphopenia ≥ grade 3 according to NCI-CTCAE v5.0 criteria. | At days 3, 7, 15 and 31 |
| Frequency of Occurrence of CPK Increase ≥ Grade 3 | Percentage of patients with CPK increase ≥ grade 3 according to NCI-CTCAE v5.0 criteria. | At days 3, 7, 15 and 31 |
| 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. | At days 3, 7, 15 and 31 |
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in the Viral Load of SARS-CoV-2 | Median change in the viral load of SARS-CoV-2 from baseline. | At days 4, 7, 15 and 31 |
| Time to Negative PCR Test for COVID-19 | Time from inclusion/randomization to date of negative PCR test for COVID-19 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Vicente Estrada, MD | Hospital San Carlos, Madrid | Principal Investigator |
| Jesús Fortún, MD | Hospital Universitario Ramon y Cajal | Principal Investigator |
| José Barberán, MD | HOSPITAL UNIVERSITARIO HM MONTEPRÍNCIPE | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Universitario Hm Montepríncipe | Boadilla del Monte | Madrid | 28660 | Spain | ||
| Hospital Germans Trias i Pujol |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35012962 | Derived | Varona JF, Landete P, Lopez-Martin JA, Estrada V, Paredes R, Guisado-Vasco P, Fernandez de Orueta L, Torralba M, Fortun J, Vates R, Barberan J, Clotet B, Ancochea J, Carnevali D, Cabello N, Porras L, Gijon P, Monereo A, Abad D, Zuniga S, Sola I, Rodon J, Vergara-Alert J, Izquierdo-Useros N, Fudio S, Pontes MJ, de Rivas B, Giron de Velasco P, Nieto A, Gomez J, Aviles P, Lubomirov R, Belgrano A, Sopesen B, White KM, Rosales R, Yildiz S, Reuschl AK, Thorne LG, Jolly C, Towers GJ, Zuliani-Alvarez L, Bouhaddou M, Obernier K, McGovern BL, Rodriguez ML, Enjuanes L, Fernandez-Sousa JM, Krogan NJ, Jimeno JM, Garcia-Sastre A. Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19. Life Sci Alliance. 2022 Jan 10;5(4):e202101200. doi: 10.26508/lsa.202101200. Print 2022 Apr. |
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Data of the final publication of the study will be shared upon request.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | 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. |
| FG002 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | Experimental 2 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Frequency of Occurrence of Neutropenia ≥ Grade 3 | Percentage of patients with Neutropenia ≥ grade 3 according to NCI-CTCAE v5.0 criteria. | Posted | Count of Participants | Participants | At days 3, 7, 15 and 31 |
|
From first administration of plitidepsin until day 31.
2 patients die during the study, one of Arm A on day 22 due to COVID-19 pneumonia and pneumomediastinum and the other of Arm C at day 30 due to disease-related acute respiratory distress syndrome.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Experimental 1 | Plitidepsin 1.5 mg / day x 3 consecutive days | 1 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaphylactic reaction | Immune system disorders | 23.1 | Systematic Assessment | Anaphylactic reaction Grade 3 in Arm A (1.5 mg plitidepsin) attributed to plitidepsin. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 23.1 | Systematic Assessment |
Small number of patients. No control group.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Development Virology Business Unit PharmaMar | PharmaMar, S.A. | +34 91 846 60 00 | clinicaltrials@pharmamar.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 29, 2020 | Jul 5, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 22, 2021 | Jul 5, 2021 | SAP_001.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D018352 | Coronavirus Infections |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| ID | Term |
|---|---|
| C098980 | plitidepsin |
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|
| Plitidepsin 2.0 mg/day | Drug | 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:
|
|
| Plitidepsin 2.5 mg/day | Drug | 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:
|
|
| At days 3, 7, 15 and 31 |
| Frequency of Occurrence of Neurotoxicity ≥ Grade 3 | Percentage of patients with Neurotoxicity ≥ grade 3 according to NCI-CTCAE v5.0 criteria. | At days 3, 7, 15 and 31 |
| 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. | At days 3, 7, 15 and 31 |
| 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. | At days 3, 7, 15 and 31. |
| Percentage of Patients in Whom Treatment Cannot be Completed. | Percentage of patients in whom treatment cannot be completed and the reasons. | At 3 days from the first dose of study treatment |
| Percentage of Patients With Adverse Events. | Percentage of patients with adverse events. | At days 3, 7, 15 and 31 |
| Percentage of Patients With Serious Adverse Events. | Percentage of patients with serious adverse events. | At days 3, 7, 15 and 31 |
| Percentage of Patients With ECG Abnormalities. | Percentage of patients with ECG abnormalities. | At days 2, 3, 4, 5, 6, 7, 15 and 31 |
| Up to 31 days + 3 days for window period |
| Mortality | Percentage of patients who die during the study | At days 7, 15 and 31 |
| Percentage of Patients Requiring Invasive Mechanical Ventilation and / or ICU Admission | Percentage of patients requiring invasive mechanical ventilation and / or ICU admission | At days 7, 15 and 31 |
| Percentage of Patients Requiring Non-invasive Mechanical Ventilation | Percentage of patients requiring non-invasive mechanical ventilation | At days 7, 15 and 31 |
| Percentage of Patients Requiring Oxygen Therapy | Percentage of patients requiring oxygen therapy | At days 7, 15 and 31 |
| Badalona |
| 08916 |
| Spain |
| Hospital Clínic de Barcelona | Barcelona | 08036 | Spain |
| Hospital de la Santa Creu i Sant Pau | Barcelona | 08041 | Spain |
| Hospital Ciudad Real | Ciudad Real | 13005 | Spain |
| Hospital Universitario de Getafe | Getafe | 28905 | Spain |
| Hospital Universitario de Guadalajara | Guadalajara | 19002 | Spain |
| Hospital Universitari Arnau de Vilanova | Lleida | 25198 | Spain |
| Hospital La Princesa | Madrid | 28006 | Spain |
| Hospital Gregorio Marañón | Madrid | 28009 | Spain |
| Hospital Ramón Y Cajal | Madrid | 28034 | Spain |
| Hospital Clínico San Carlos | Madrid | 28040 | Spain |
| Hosptial Quironsalud Madrid | Madrid | 28223 | Spain |
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.
| BG002 | 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. |
| BG003 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Number of comorbidities | Number | Participants |
|
| Comorbidities | Number | Participants |
|
| Clinical status at randomization | Number | Participants |
|
| Chest x-rays | Number | Participants |
|
| Body temperature | Median | Full Range | Degrees Celsius |
|
| Systolic blood pressure | Median | Full Range | mmHg |
|
| Diastolic blood pressure | Median | Full Range | mmHg |
|
| Heart rate | Median | Full Range | Bpm |
|
| Respiratory rate | Median | Full Range | Bpm |
|
| Oxygen saturation at room air | Oxygen saturation at room air has been analyzed for the 22 patients who did not requiere supplementary O2. | Median | Full Range | Percentage |
|
| On supplementary O2 | Number | Participants |
|
| PaO2/FiO2 | Median | Full Range | Ratio |
|
| White Blood Cells (WBC) | Median | Full Range | 10^9 cells/liter |
|
| Platelet count | Median | Full Range | 10^9 cells/liter |
|
| Lymphocytes | Median | Full Range | 10^9 cells/liter |
|
| D-dimer | Median | Full Range | ng/mL |
|
| Ferritin | Median | Full Range | ng/ml |
|
| C-reactive protein | Median | Full Range | mg/L |
|
| Serum creatinine | Median | Inter-Quartile Range | mg/dL |
|
| Alanine aminotransferase | Median | Full Range | x Upper Limit of Normal (ULN) |
|
| Aspartate aminotransferase | Median | Full Range | x Upper Limit of Normal (ULN) |
|
| Lactate dehydrogenase | Median | Full Range | x Upper Limit of Normal (ULN) |
|
| Creatine phosphokinase | Median | Full Range | x Upper Limit of Normal (ULN) |
|
| Viral load | Results available por 44 patients: 1 patient (in 2.0 mg cohort) did not have baseline viral load asessment by central lab. | Median | Full Range | Log10 copies/mL |
|
| OG003 | Total | All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety. |
|
|
| Primary | Frequency of Occurrence of Thrombocytopenia ≥ Grade 3 | Percentage of patients with Thrombocytopenia ≥ grade 3 according to NCI-CTCAE v5.0 criteria. | Posted | Count of Participants | Participants | At days 3, 7, 15 and 31 |
|
|
|
| Primary | Frequency of Occurrence of Anemia ≥ Grade 3 | Percentage of patients with Anemia ≥ grade 3 according to NCI-CTCAE v5.0 criteria. | Posted | Count of Participants | Participants | At days 3, 7, 15 and 31 |
|
|
|
| Primary | Frequency of Occurrence of Lymphopenia ≥ Grade 3 | Percentage of patients with Lymphopenia ≥ grade 3 according to NCI-CTCAE v5.0 criteria. | Posted | Count of Participants | Participants | At days 3, 7, 15 and 31 |
|
|
|
| Primary | Frequency of Occurrence of CPK Increase ≥ Grade 3 | Percentage of patients with CPK increase ≥ grade 3 according to NCI-CTCAE v5.0 criteria. | Posted | Count of Participants | Participants | At days 3, 7, 15 and 31 |
|
|
|
| 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. | Posted | Count of Participants | Participants | At days 3, 7, 15 and 31 |
|
|
|
| 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. | Posted | Count of Participants | Participants | At days 3, 7, 15 and 31 |
|
|
|
| Primary | Frequency of Occurrence of Neurotoxicity ≥ Grade 3 | Percentage of patients with Neurotoxicity ≥ grade 3 according to NCI-CTCAE v5.0 criteria. | Posted | Count of Participants | Participants | At days 3, 7, 15 and 31 |
|
|
|
| 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. | Posted | Count of Participants | Participants | At days 3, 7, 15 and 31 |
|
|
|
| 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. | Posted | Count of Participants | Participants | At days 3, 7, 15 and 31. |
|
|
|
| Primary | Percentage of Patients in Whom Treatment Cannot be Completed. | Percentage of patients in whom treatment cannot be completed and the reasons. | Posted | Count of Participants | Participants | At 3 days from the first dose of study treatment |
|
|
|
| Primary | Percentage of Patients With Adverse Events. | Percentage of patients with adverse events. | Posted | Count of Participants | Participants | At days 3, 7, 15 and 31 |
|
|
|
| Primary | Percentage of Patients With Serious Adverse Events. | Percentage of patients with serious adverse events. | Posted | Count of Participants | Participants | At days 3, 7, 15 and 31 |
|
|
|
| Primary | Percentage of Patients With ECG Abnormalities. | Percentage of patients with ECG abnormalities. | Posted | Count of Participants | Participants | At days 2, 3, 4, 5, 6, 7, 15 and 31 |
|
|
|
| Secondary | Change in the Viral Load of SARS-CoV-2 | Median change in the viral load of SARS-CoV-2 from baseline. | 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. | Posted | Median | Standard Deviation | Log10 copies/mL | At days 4, 7, 15 and 31 |
|
|
|
| Secondary | Time to Negative PCR Test for COVID-19 | Time from inclusion/randomization to date of negative PCR test for COVID-19 | 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. | Posted | Mean | Full Range | Days | Up to 31 days + 3 days for window period |
|
|
|
| Secondary | Mortality | Percentage of patients who die during the study | 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. | Posted | Count of Participants | Participants | At days 7, 15 and 31 |
|
|
|
| Secondary | Percentage of Patients Requiring Invasive Mechanical Ventilation and / or ICU Admission | Percentage of patients requiring invasive mechanical ventilation and / or ICU admission | 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. | Posted | Count of Participants | Participants | At days 7, 15 and 31 |
|
|
|
| Secondary | Percentage of Patients Requiring Non-invasive Mechanical Ventilation | Percentage of patients requiring non-invasive mechanical ventilation | 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. | Posted | Count of Participants | Participants | At days 7, 15 and 31 |
|
|
|
| Secondary | Percentage of Patients Requiring Oxygen Therapy | Percentage of patients requiring oxygen therapy | 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. | Posted | Count of Participants | Participants | At days 7, 15 and 31 |
|
|
|
| 15 |
| 6 |
| 15 |
| 15 |
| 15 |
| EG001 | Experimental 2 | Plitidepsin 2.0 mg / day x 3 consecutive days | 0 | 15 | 1 | 15 | 14 | 15 |
| EG002 | Experimental 3 | Plitidepsin 2.5 mg / day x 3 consecutive days | 1 | 15 | 3 | 15 | 15 | 15 |
| EG003 | Total | All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety. | 2 | 45 | 10 | 45 | 44 | 45 |
|
| Acute respiratory distress syndrome | Respiratory, thoracic and mediastinal disorders | 23.1 | Systematic Assessment | 1 Acute respiratory distress syndrome grade 3 and 1 grade 4 and 1 grade 5 in the same patient in Arm A (1.5 mg plitidepsin), 1 grade 4 in Arm B (2 mg plitidepsin) and 1 grade 4 in Arm C (2.5 mg plitidepsin). |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 23.1 | Systematic Assessment | Acute respiratory failure grade 5 in Arm C (2.5 mg plitidepsin) |
|
| Status epilepticus | Nervous system disorders | 23.1 | Systematic Assessment | Status epilepticus grade 3 in Arm C (2.5 mg plitidepsin) |
|
| Pneumomediastinum | Respiratory, thoracic and mediastinal disorders | 23.1 | Systematic Assessment |
|
| Condition aggravated | General disorders | 23.1 | Systematic Assessment | Condition aggravated grade 3 in Arm A (1.5 mg plitidepsin) |
|
| Pyelonephritis | Infections and infestations | 23.1 | Systematic Assessment |
|
| COVID-19 pneumonia | Infections and infestations | 23.1 | Systematic Assessment | 1 COVID-19 pneumonia grade 3 in Arm A (1.5 mg ) and 1 grade 3 and 1 grade 5 in the same patient in Arm C (2.5 mg plitidepsin). |
|
| Superinfection bacterial | Infections and infestations | 23.1 | Systematic Assessment |
|
| Leukocytosis | Blood and lymphatic system disorders | 23.1 | Systematic Assessment | 1 Leukocytosis grade 3 in Arm C (2.5 mg plitidepsin). |
|
| Lymphopenia | Blood and lymphatic system disorders | 23.1 | Systematic Assessment |
|
| Neutrophilia | Blood and lymphatic system disorders | 23.1 | Systematic Assessment |
|
| Atrial fibrillation | Cardiac disorders | 23.1 | Systematic Assessment |
|
| Tachycardia | Cardiac disorders | 23.1 | Systematic Assessment |
|
| Vertigo | Ear and labyrinth disorders | 23.1 | Systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | 23.1 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | 23.1 | Systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | 23.1 | Systematic Assessment | 1 diarrhoea grade 3 in Arm A (1.5 mg plitidepsin) was attributed to plitidepsin. |
|
| Dyspepsia | Gastrointestinal disorders | 23.1 | Systematic Assessment |
|
| Nausea | Gastrointestinal disorders | 23.1 | Systematic Assessment |
|
| Rectal haemorrhage | Gastrointestinal disorders | 23.1 | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | 23.1 | Systematic Assessment |
|
| Hypoalbuminaemia | Hepatobiliary disorders | 23.1 | Systematic Assessment |
|
| Bacteremia | Infections and infestations | 23.1 | Systematic Assessment | 1 Bacteremia grade 3 in Arm C (2.5 mg plitidepsin). |
|
| COVID-19 pneumonia | Infections and infestations | 23.1 | Systematic Assessment |
|
| Pneumonia | Infections and infestations | 23.1 | Systematic Assessment | 1 Pneumonia grade 3 in Arm A (1.5 mg plitidepsin). |
|
| Skin candida | Infections and infestations | 23.1 | Systematic Assessment |
|
| Urinary tract infection | Infections and infestations | 23.1 | Systematic Assessment | 1 Urinary tract infection grade 3 in Arm C (2.5 mg plitidepsin). |
|
| Viral infection | Infections and infestations | 23.1 | Systematic Assessment |
|
| Fall | Injury, poisoning and procedural complications | 23.1 | Systematic Assessment |
|
| Alkaline phosphatase increased | Investigations | 23.1 | Systematic Assessment |
|
| ALT increased | Investigations | 23.1 | Systematic Assessment | 1 ALT increased grade 3 in Arm B (2 mg plitidepsin). |
|
| Amylase increased | Investigations | 23.1 | Systematic Assessment |
|
| AST increased | Investigations | 23.1 | Systematic Assessment |
|
| Blood cholesterol increased | Investigations | 23.1 | Systematic Assessment |
|
| Blood creatinine increased | Investigations | 23.1 | Systematic Assessment |
|
| Blood fibrinogen increased | Investigations | 23.1 | Systematic Assessment |
|
| Blood glucose increased | Investigations | 23.1 | Systematic Assessment |
|
| CPK increased | Investigations | 23.1 | Systematic Assessment |
|
| C-reactive protein increased | Investigations | 23.1 | Systematic Assessment | 1 C-reactive protein increased grade 3 in Arm A (1.5 mg plitidepsin). |
|
| Ferritin increased | Investigations | 23.1 | Systematic Assessment | 1 Ferritin increased grade 3 in Arm A (1.5 mg plitidepsin). |
|
| GGT increased | Investigations | 23.1 | Systematic Assessment | 1 GGT increased grade 3 in Arm A (1.5 mg plitidepsin) and 2 grade 3 in Arm B (2 mg plitidepsin) |
|
| LDH increased | Investigations | 23.1 | Systematic Assessment |
|
| LDL increased | Investigations | 23.1 | Systematic Assessment |
|
| Oxygen saturation decreased | Investigations | 23.1 | Systematic Assessment |
|
| Transaminases increased | Investigations | 23.1 | Systematic Assessment |
|
| Triglycerides increased | Investigations | 23.1 | Systematic Assessment |
|
| Fibrin D dimer increased | Investigations | 23.1 | Systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | 23.1 | Systematic Assessment |
|
| Dehydration | Metabolism and nutrition disorders | 23.1 | Systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | 23.1 | Systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | 23.1 | Systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | 23.1 | Systematic Assessment |
|
| Malnutrition | Metabolism and nutrition disorders | 23.1 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | 23.1 | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | 23.1 | Systematic Assessment |
|
| Muscular weakness | Musculoskeletal and connective tissue disorders | 23.1 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | 23.1 | Systematic Assessment |
|
| Dizziness | Nervous system disorders | 23.1 | Systematic Assessment |
|
| Dysgeusia | Nervous system disorders | 23.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | 23.1 | Systematic Assessment |
|
| Insomnia | Nervous system disorders | 23.1 | Systematic Assessment |
|
| Migraine | Nervous system disorders | 23.1 | Systematic Assessment |
|
| Paraesthesia | Nervous system disorders | 23.1 | Systematic Assessment |
|
| Presyncope | Nervous system disorders | 23.1 | Systematic Assessment |
|
| Somnolence | Nervous system disorders | 23.1 | Systematic Assessment |
|
| Agitation | Psychiatric disorders | 23.1 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | 23.1 | Systematic Assessment |
|
| Delirium | Psychiatric disorders | 23.1 | Systematic Assessment |
|
| Pollakiuria | Renal and urinary disorders | 23.1 | Systematic Assessment |
|
| Prerenal failure | Renal and urinary disorders | 23.1 | Systematic Assessment |
|
| Renal impairment | Renal and urinary disorders | 23.1 | Systematic Assessment | 1 Renal impairment grade 3 in Arm A (1.5 mg plitidepsin). |
|
| Breast engorgement | Reproductive system and breast disorders | 23.1 | Systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 23.1 | Systematic Assessment |
|
| Chest discomfort | Respiratory, thoracic and mediastinal disorders | 23.1 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | 23.1 | Systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 23.1 | Systematic Assessment |
|
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 23.1 | Systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | 23.1 | Systematic Assessment |
|
| Respiratory distress | Respiratory, thoracic and mediastinal disorders | 23.1 | Systematic Assessment |
|
| Tachypnoea | Respiratory, thoracic and mediastinal disorders | 23.1 | Systematic Assessment |
|
| Skin ulcer | Skin and subcutaneous tissue disorders | 23.1 | Systematic Assessment |
|
| Hypertension | Vascular disorders | 23.1 | Systematic Assessment |
|
| Hypotension | Vascular disorders | 23.1 | Systematic Assessment |
|
| Phlebitis | Vascular disorders | 23.1 | Systematic Assessment |
|
| Thrombophlebitis | Vascular disorders | 23.1 | Systematic Assessment |
|
| Asthenia | General disorders | 23.1 | Systematic Assessment |
|
| Chest discomfort | General disorders | 23.1 | Systematic Assessment |
|
| Pyrexia | General disorders | 23.1 | Systematic Assessment |
|
| Malaise | General disorders | 23.1 | Systematic Assessment |
|
| Temperature regulation disorder | General disorders | 23.1 | Systematic Assessment |
|
| Fatigue | General disorders | 23.1 | Systematic Assessment |
|
| Platelet count decreased | Investigations | 23.1 | Systematic Assessment |
|
| Neutrophil count increased | Investigations | 23.1 | Systematic Assessment |
|
| Interleukin level increased | Investigations | 23.1 | Systematic Assessment |
|
| Lipase increased | Investigations | 23.1 | Systematic Assessment |
|
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | 23.1 | Systematic Assessment |
|
| Pleuritic pain | Respiratory, thoracic and mediastinal disorders | 23.1 | Systematic Assessment |
|
| Pneumothorax spontaneous | Respiratory, thoracic and mediastinal disorders | 23.1 | Systematic Assessment |
|
| Tenosynovitis | Musculoskeletal and connective tissue disorders | 23.1 | Systematic Assessment |
|
Not provided
| D014777 |
| Virus Diseases |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Title | Measurements |
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| Title | Measurements |
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| Title | Measurements |
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| Title | Measurements |
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| Title | Measurements |
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| Title | Measurements |
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| Title | Measurements |
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| Title | Measurements |
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| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
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| Title | Measurements |
|---|---|
|
| Day 7 |
|
| Day 15 |
|
| Day 31 |
|
| Day 7 |
|
| Day 15 |
|
| Day 31 |
|
| Day 7 |
|
| Day 15 |
|
| Day 31 |
|
| Day 7 |
|
| Day 15 |
|
| Day 31 |
|
| ALT increased Day 7 |
|
| ALT increased Day 15 |
|
| ALT increased Day 31 |
|
| AST increased Day 3 |
|
| AST increased Day 7 |
|
| AST increased Day 15 |
|
| AST increased Day 31 |
|
| Day 7 |
|
| Day 15 |
|
| Day 31 |
|
| Day 7 |
|
| Day 15 |
|
| Day 31 |
|
| Day 7 |
|
| Day 15 |
|
| Day 31 |
|
| Leukocytosis day 7 |
|
| Leukocytosis day 15 |
|
| Leukocytosis day 31 |
|
| Diarrhoea day 3 |
|
| Diarrhoea day 7 |
|
| Diarrhoea day 15 |
|
| Diarrhoea day 31 |
|
| Condition aggravated day 3 |
|
| Condition aggravated day 7 |
|
| Condition aggravated day 15 |
|
| Condition aggravated day 31 |
|
| Anaphylactic reaction day 3 |
|
| Anaphylactic reaction day 7 |
|
| Anaphylactic reaction day 15 |
|
| Anaphylactic reaction day 31 |
|
| Bacteraemia day 3 |
|
| Bacteraemia day 7 |
|
| Bacteraemia day 15 |
|
| Bacteraemia day 31 |
|
| COVID-19 pneumonia day 3 |
|
| COVID-19 pneumonia day 7 |
|
| COVID-19 pneumonia day 15 |
|
| COVID-19 pneumonia day 31 |
|
| Pneumonia day 3 |
|
| Pneumonia day 7 |
|
| Pneumonia day 15 |
|
| Pneumonia day 31 |
|
| Superinfection bacterial day 3 |
|
| Superinfection bacterial day 7 |
|
| Superinfection bacterial day 15 |
|
| Superinfection bacterial day 31 |
|
| Urinary tract infection day 3 |
|
| Urinary tract infection day 7 |
|
| Urinary tract infection day 15 |
|
| Urinary tract infection day 31 |
|
| C-reactive protein increased day 3 |
|
| C-reactive protein increased day 7 |
|
| C-reactive protein increased day 15 |
|
| C-reactive protein increased day 31 |
|
| Gamma-glutamyltransferase increased day 3 |
|
| Gamma-glutamyltransferase increased day 7 |
|
| Gamma-glutamyltransferase increased day 15 |
|
| Gamma-glutamyltransferase increased day 31 |
|
| Serum ferritin increased day 3 |
|
| Serum ferritin increased day 7 |
|
| Serum ferritin increased day 15 |
|
| Serum ferritin increased day 31 |
|
| Hyperglycaemia day 3 |
|
| Hyperglycaemia day 7 |
|
| Hyperglycaemia day 15 |
|
| Hyperglycaemia day 31 |
|
| Status epilepticus day 3 |
|
| Status epilepticus day 7 |
|
| Status epilepticus day 15 |
|
| Status epilepticus day 31 |
|
| Acute respiratory distress syndrome day 3 |
|
| Acute respiratory distress syndrome day 7 |
|
| Acute respiratory distress syndrome day 15 |
|
| Acute respiratory distress syndrome day 31 |
|
| Pneumomediastinum day 3 |
|
| Pneumomediastinum day 7 |
|
| Pneumomediastinum day 15 |
|
| Pneumomediastinum day 31 |
|
| Respiratory distress day 3 |
|
| Respiratory distress day 7 |
|
| Respiratory distress day 15 |
|
| Respiratory distress day 31 |
|
| Day 7 |
|
| Day 15 |
|
| Day 31 |
|
| Day 7 |
|
| Day 15 |
|
| Day 31 |
|
| Day 3 |
|
| Day 4 |
|
| Day 5 |
|
| Day 6 |
|
| Day 7 |
|
| Day 15 |
|
| Day 31 |
|
| Day 7 |
|
| Day 15 |
|
| Day 31 |
|
| Day 15 |
|
| Day 31 |
|
| Day 15 |
|
| Day 31 |
|
| Day 15 |
|
| Day 31 |
|
| Day 15 |
|
| Day 31 |
|