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APLICOV-PC: Proof of Concept Study to Evaluate the Safety Profile of Plitidepsin in Patients With COVID-19

Sponsor
PharmaMar (Industry)
Overall Status
Completed
CT.gov ID
NCT04382066
Collaborator
Apices Soluciones S.L. (Industry)
46
Enrollment
13
Locations
3
Arms
6.5
Actual Duration (Months)
3.5
Patients Per Site
0.5
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Plitidepsin 1.5 mg/day
  • Drug: Plitidepsin 2.0 mg/day
  • Drug: Plitidepsin 2.5 mg/day
 Phase 1

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
46 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Multicenter, Randomized, Parallel and Proof of Concept Study to Evaluate the Safety Profile of Three Doses of Plitidepsin in Patients With COVID-19 Requiring Hospitalization
Actual Study Start Date :
May 12, 2020
Actual Primary Completion Date :
Nov 26, 2020
Actual Study Completion Date :
Nov 26, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Experimental 1

Plitidepsin 1.5 mg / day x 3 consecutive days

Drug: 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. 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.
Experimental: Experimental 2

Plitidepsin 2.0 mg / day x 3 consecutive days

Drug: 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. 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.
Experimental: Experimental 3

Plitidepsin 2.5 mg / day x 3 consecutive days

Drug: 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. 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.

Outcome Measures

Primary Outcome Measures

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Percentage of Patients With Adverse Events. [At days 3, 7, 15 and 31]

    Percentage of patients with adverse events.

  13. Percentage of Patients With Serious Adverse Events. [At days 3, 7, 15 and 31]

    Percentage of patients with serious adverse events.

  14. Percentage of Patients With ECG Abnormalities. [At days 2, 3, 4, 5, 6, 7, 15 and 31]

    Percentage of patients with ECG abnormalities.

Secondary Outcome Measures

  1. 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.

  2. 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

  3. Mortality [At days 7, 15 and 31]

    Percentage of patients who die during the study

  4. 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

  5. Percentage of Patients Requiring Non-invasive Mechanical Ventilation [At days 7, 15 and 31]

    Percentage of patients requiring non-invasive mechanical ventilation

  6. Percentage of Patients Requiring Oxygen Therapy [At days 7, 15 and 31]

    Percentage of patients requiring oxygen therapy

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts 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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Hospital Universitario Hm Montepríncipe Boadilla Del Monte Madrid Spain 28660
2 Hospital Germans Trias i Pujol Badalona Spain 08916
3 Hospital Clínic de Barcelona Barcelona Spain 08036
4 Hospital de la Santa Creu i Sant Pau Barcelona Spain 08041
5 Hospital Ciudad Real Ciudad Real Spain 13005
6 Hospital Universitario de Getafe Getafe Spain 28905
7 Hospital Universitario de Guadalajara Guadalajara Spain 19002
8 Hospital Universitari Arnau de Vilanova Lleida Spain 25198
9 Hospital La Princesa Madrid Spain 28006
10 Hospital Gregorio Marañón Madrid Spain 28009
11 Hospital Ramón Y Cajal Madrid Spain 28034
12 Hospital Clínico San Carlos Madrid Spain 28040
13 Hosptial Quironsalud Madrid Madrid Spain 28223

Sponsors and Collaborators

  • PharmaMar
  • Apices Soluciones S.L.

Investigators

  • Principal Investigator: 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

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
PharmaMar
ClinicalTrials.gov Identifier:
NCT04382066
Other Study ID Numbers:
  • APL-D-002-20
  • 2020-001993-31
First Posted:
May 11, 2020
Last Update Posted:
Aug 23, 2022
Last Verified:
Jul 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by PharmaMar
Plitidepsin
COVID-19
SARS-COV-2
Coronavirus
Additional relevant MeSH terms:
COVID-19

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Experimental 1 Experimental 2 Experimental 3
Arm/Group Description 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. 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. 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.
Period Title: Overall Study
STARTED 15 15 15
Completed 3-day Treatment 14 15 15
COMPLETED 13 15 14
NOT COMPLETED 2 0 1

Baseline Characteristics

Arm/Group Title Experimental 1 Experimental 2 Experimental 3 Total
Arm/Group Description 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. 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. 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. Total of all reporting groups
Overall Participants 15 15 15 45
Age (Count of Participants)
<=18 years
0
0%
0
0%
0
0%
0
0%
Between 18 and 65 years
12
80%
13
86.7%
11
73.3%
36
80%
>=65 years
3
20%
2
13.3%
4
26.7%
9
20%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]
51
49
53
52
Sex: Female, Male (Count of Participants)
Female
4
26.7%
4
26.7%
7
46.7%
15
33.3%
Male
11
73.3%
11
73.3%
8
53.3%
30
66.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
0
0%
Asian
0
0%
0
0%
0
0%
0
0%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
0
0%
Black or African American
0
0%
0
0%
0
0%
0
0%
White
15
100%
15
100%
15
100%
45
100%
More than one race
0
0%
0
0%
0
0%
0
0%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
Region of Enrollment (participants) [Number]
Spain
15
100%
15
100%
15
100%
45
100%
Number of comorbidities (Number) [Number]
None
5
33.3%
2
13.3%
2
13.3%
9
20%
One
2
13.3%
7
46.7%
6
40%
15
33.3%
Two or more
8
53.3%
6
40%
7
46.7%
21
46.7%
Comorbidities (Number) [Number]
Cardiac disease
1
6.7%
0
0%
1
6.7%
2
4.4%
Kidney disease
0
0%
1
6.7%
0
0%
1
2.2%
Lung disease (COPD)
1
6.7%
1
6.7%
1
6.7%
3
6.7%
Asthma
2
13.3%
0
0%
3
20%
5
11.1%
Diabetes
1
6.7%
5
33.3%
2
13.3%
8
17.8%
Hypertension
2
13.3%
2
13.3%
5
33.3%
9
20%
Obesity
1
6.7%
5
33.3%
4
26.7%
10
22.2%
Clinical status at randomization (Number) [Number]
Mild COVID-19 infection
2
13.3%
3
20%
1
6.7%
6
13.3%
Moderate COVID-19 infection
8
53.3%
7
46.7%
8
53.3%
23
51.1%
Severe COVID-19 infection
5
33.3%
5
33.3%
6
40%
16
35.6%
Chest x-rays (Number) [Number]
Abnormal
15
100%
13
86.7%
13
86.7%
41
91.1%
Bilateral pneumonia
11
73.3%
10
66.7%
11
73.3%
32
71.1%
Body temperature (Degrees Celsius) [Median (Full Range) ]
Median (Full Range) [Degrees Celsius]
36.5
37.0
36.2
36.5
Systolic blood pressure (mmHg) [Median (Full Range) ]
Median (Full Range) [mmHg]
113
115
124
119
Diastolic blood pressure (mmHg) [Median (Full Range) ]
Median (Full Range) [mmHg]
69
71
78
72
Heart rate (Bpm) [Median (Full Range) ]
Median (Full Range) [Bpm]
84
78
82
82
Respiratory rate (Bpm) [Median (Full Range) ]
Median (Full Range) [Bpm]
17
18
16.5
17
Oxygen saturation at room air (Percentage) [Median (Full Range) ]
Median (Full Range) [Percentage]
95
95
96.5
95.5
On supplementary O2 (Number) [Number]
Number [Participants]
6
40%
8
53.3%
9
60%
23
51.1%
PaO2/FiO2 (Ratio) [Median (Full Range) ]
Median (Full Range) [Ratio]
358
352
343
350
White Blood Cells (WBC) (10^9 cells/liter) [Median (Full Range) ]
Median (Full Range) [10^9 cells/liter]
4.4
5.4
7.1
5.5
Platelet count (10^9 cells/liter) [Median (Full Range) ]
Median (Full Range) [10^9 cells/liter]
183
168
244
183
Lymphocytes (10^9 cells/liter) [Median (Full Range) ]
Median (Full Range) [10^9 cells/liter]
0.9
1.1
1.1
1.0
D-dimer (ng/mL) [Median (Full Range) ]
Median (Full Range) [ng/mL]
330
463
415
405
Ferritin (ng/ml) [Median (Full Range) ]
Median (Full Range) [ng/ml]
408
597
363
412
C-reactive protein (mg/L) [Median (Full Range) ]
Median (Full Range) [mg/L]
17.7
67.2
32.6
32.7
Serum creatinine (mg/dL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [mg/dL]
0.8
0.8
0.8
0.8
Alanine aminotransferase (x Upper Limit of Normal (ULN)) [Median (Full Range) ]
Median (Full Range) [x Upper Limit of Normal (ULN)]
0.9
0.8
0.7
0.8
Aspartate aminotransferase (x Upper Limit of Normal (ULN)) [Median (Full Range) ]
Median (Full Range) [x Upper Limit of Normal (ULN)]
0.8
0.9
0.7
0.8
Lactate dehydrogenase (x Upper Limit of Normal (ULN)) [Median (Full Range) ]
Median (Full Range) [x Upper Limit of Normal (ULN)]
1.0
1.0
1.2
1.0
Creatine phosphokinase (x Upper Limit of Normal (ULN)) [Median (Full Range) ]
Median (Full Range) [x Upper Limit of Normal (ULN)]
0.4
0.3
0.4
0.4
Viral load (Log10 copies/mL) [Median (Full Range) ]
Median (Full Range) [Log10 copies/mL]
6.3
6.2
5.7
6.1

Outcome Measures

1. Primary Outcome
Title Frequency of Occurrence of Neutropenia ≥ Grade 3
Description Percentage of patients with Neutropenia ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time Frame At days 3, 7, 15 and 31

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Experimental 1 Experimental 2 Experimental 3 Total
Arm/Group Description Plitidepsin 1.5 mg / day x 3 consecutive days Plitidepsin 2.0 mg / day x 3 consecutive days Plitidepsin 2.5 mg / day x 3 consecutive days All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety.
Measure Participants 15 15 15 45
Day 3
0
0%
0
0%
0
0%
0
0%
Day 7
0
0%
0
0%
0
0%
0
0%
Day 15
0
0%
0
0%
0
0%
0
0%
Day 31
0
0%
0
0%
0
0%
0
0%
2. Primary Outcome
Title Frequency of Occurrence of Thrombocytopenia ≥ Grade 3
Description Percentage of patients with Thrombocytopenia ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time Frame At days 3, 7, 15 and 31

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Experimental 1 Experimental 2 Experimental 3 Total
Arm/Group Description Plitidepsin 1.5 mg / day x 3 consecutive days Plitidepsin 2.0 mg / day x 3 consecutive days Plitidepsin 2.5 mg / day x 3 consecutive days All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety.
Measure Participants 15 15 15 45
Day 3
0
0%
0
0%
0
0%
0
0%
Day 7
0
0%
0
0%
0
0%
0
0%
Day 15
0
0%
0
0%
0
0%
0
0%
Day 31
0
0%
0
0%
0
0%
0
0%
3. Primary Outcome
Title Frequency of Occurrence of Anemia ≥ Grade 3
Description Percentage of patients with Anemia ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time Frame At days 3, 7, 15 and 31

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Experimental 1 Experimental 2 Experimental 3 Total
Arm/Group Description Plitidepsin 1.5 mg / day x 3 consecutive days Plitidepsin 2.0 mg / day x 3 consecutive days Plitidepsin 2.5 mg / day x 3 consecutive days All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety.
Measure Participants 15 15 15 45
Day 3
0
0%
0
0%
0
0%
0
0%
Day 7
0
0%
0
0%
0
0%
0
0%
Day 15
0
0%
0
0%
0
0%
0
0%
Day 31
0
0%
0
0%
0
0%
0
0%
4. Primary Outcome
Title Frequency of Occurrence of Lymphopenia ≥ Grade 3
Description Percentage of patients with Lymphopenia ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time Frame At days 3, 7, 15 and 31

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Experimental 1 Experimental 2 Experimental 3 Total
Arm/Group Description Plitidepsin 1.5 mg / day x 3 consecutive days Plitidepsin 2.0 mg / day x 3 consecutive days Plitidepsin 2.5 mg / day x 3 consecutive days All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety.
Measure Participants 15 15 15 45
Day 3
0
0%
0
0%
0
0%
0
0%
Day 7
0
0%
0
0%
0
0%
0
0%
Day 15
0
0%
0
0%
0
0%
0
0%
Day 31
0
0%
0
0%
0
0%
0
0%
5. Primary Outcome
Title Frequency of Occurrence of CPK Increase ≥ Grade 3
Description Percentage of patients with CPK increase ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time Frame At days 3, 7, 15 and 31

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Experimental 1 Experimental 2 Experimental 3 Total
Arm/Group Description Plitidepsin 1.5 mg / day x 3 consecutive days Plitidepsin 2.0 mg / day x 3 consecutive days Plitidepsin 2.5 mg / day x 3 consecutive days All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety.
Measure Participants 15 15 15 45
Day 3
0
0%
0
0%
0
0%
0
0%
Day 7
0
0%
0
0%
0
0%
0
0%
Day 15
0
0%
0
0%
0
0%
0
0%
Day 31
0
0%
0
0%
0
0%
0
0%
6. Primary Outcome
Title Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3
Description 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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Experimental 1 Experimental 2 Experimental 3 Total
Arm/Group Description Plitidepsin 1.5 mg / day x 3 consecutive days Plitidepsin 2.0 mg / day x 3 consecutive days Plitidepsin 2.5 mg / day x 3 consecutive days All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety.
Measure Participants 15 15 15 45
ALT increased Day 3
0
0%
0
0%
0
0%
0
0%
ALT increased Day 7
0
0%
0
0%
0
0%
0
0%
ALT increased Day 15
0
0%
1
6.7%
0
0%
1
2.2%
ALT increased Day 31
0
0%
1
6.7%
0
0%
1
2.2%
AST increased Day 3
0
0%
0
0%
0
0%
0
0%
AST increased Day 7
0
0%
0
0%
0
0%
0
0%
AST increased Day 15
0
0%
0
0%
0
0%
0
0%
AST increased Day 31
0
0%
0
0%
0
0%
0
0%
7. Primary Outcome
Title Frequency of Occurrence of Increase Total Bilirubin or Direct Bilirubin ≥ Grade 3
Description 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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Experimental 1 Experimental 2 Experimental 3 Total
Arm/Group Description Plitidepsin 1.5 mg / day x 3 consecutive days Plitidepsin 2.0 mg / day x 3 consecutive days Plitidepsin 2.5 mg / day x 3 consecutive days All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety.
Measure Participants 15 15 15 45
Day 3
0
0%
0
0%
0
0%
0
0%
Day 7
0
0%
0
0%
0
0%
0
0%
Day 15
0
0%
0
0%
0
0%
0
0%
Day 31
0
0%
0
0%
0
0%
0
0%
8. Primary Outcome
Title Frequency of Occurrence of Neurotoxicity ≥ Grade 3
Description Percentage of patients with Neurotoxicity ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time Frame At days 3, 7, 15 and 31

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Experimental 1 Experimental 2 Experimental 3 Total
Arm/Group Description Plitidepsin 1.5 mg / day x 3 consecutive days Plitidepsin 2.0 mg / day x 3 consecutive days Plitidepsin 2.5 mg / day x 3 consecutive days All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety.
Measure Participants 15 15 15 45
Day 3
0
0%
0
0%
0
0%
0
0%
Day 7
0
0%
0
0%
0
0%
0
0%
Day 15
0
0%
0
0%
0
0%
0
0%
Day 31
0
0%
0
0%
0
0%
0
0%
9. Primary Outcome
Title Frequency of Occurrence of QT-QTc Interval Extension ≥ Grade 3
Description 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

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Experimental 1 Experimental 2 Experimental 3 Total
Arm/Group Description Plitidepsin 1.5 mg / day x 3 consecutive days Plitidepsin 2.0 mg / day x 3 consecutive days Plitidepsin 2.5 mg / day x 3 consecutive days All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety.
Measure Participants 15 15 15 45
Day 3
0
0%
0
0%
0
0%
0
0%
Day 7
0
0%
0
0%
0
0%
0
0%
Day 15
0
0%
0
0%
0
0%
0
0%
Day 31
0
0%
0
0%
0
0%
0
0%
10. Primary Outcome
Title Frequency of Occurrence of Other Adverse Events ≥ Grade 3
Description 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.

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Experimental 1 Experimental 2 Experimental 3 Total
Arm/Group Description Plitidepsin 1.5 mg / day x 3 consecutive days Plitidepsin 2.0 mg / day x 3 consecutive days Plitidepsin 2.5 mg / day x 3 consecutive days All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety.
Measure Participants 15 15 15 45
Leukocytosis day 3
0
0%
0
0%
1
6.7%
1
2.2%
Leukocytosis day 7
0
0%
0
0%
1
6.7%
1
2.2%
Leukocytosis day 15
0
0%
0
0%
1
6.7%
1
2.2%
Leukocytosis day 31
0
0%
0
0%
1
6.7%
1
2.2%
Diarrhoea day 3
0
0%
0
0%
1
6.7%
1
2.2%
Diarrhoea day 7
0
0%
0
0%
1
6.7%
1
2.2%
Diarrhoea day 15
0
0%
0
0%
1
6.7%
1
2.2%
Diarrhoea day 31
0
0%
0
0%
1
6.7%
1
2.2%
Condition aggravated day 3
1
6.7%
0
0%
0
0%
1
2.2%
Condition aggravated day 7
1
6.7%
0
0%
0
0%
1
2.2%
Condition aggravated day 15
1
6.7%
0
0%
0
0%
1
2.2%
Condition aggravated day 31
1
6.7%
0
0%
0
0%
1
2.2%
Anaphylactic reaction day 3
1
6.7%
0
0%
0
0%
1
2.2%
Anaphylactic reaction day 7
1
6.7%
0
0%
0
0%
1
2.2%
Anaphylactic reaction day 15
1
6.7%
0
0%
0
0%
1
2.2%
Anaphylactic reaction day 31
1
6.7%
0
0%
0
0%
1
2.2%
Bacteraemia day 3
0
0%
0
0%
0
0%
0
0%
Bacteraemia day 7
0
0%
0
0%
1
6.7%
1
2.2%
Bacteraemia day 15
0
0%
0
0%
1
6.7%
1
2.2%
Bacteraemia day 31
0
0%
0
0%
1
6.7%
1
2.2%
COVID-19 pneumonia day 3
0
0%
0
0%
0
0%
0
0%
COVID-19 pneumonia day 7
0
0%
0
0%
1
6.7%
1
2.2%
COVID-19 pneumonia day 15
1
6.7%
0
0%
1
6.7%
2
4.4%
COVID-19 pneumonia day 31
1
6.7%
0
0%
1
6.7%
2
4.4%
Pneumonia day 3
0
0%
0
0%
0
0%
0
0%
Pneumonia day 7
0
0%
0
0%
0
0%
0
0%
Pneumonia day 15
1
6.7%
0
0%
0
0%
1
2.2%
Pneumonia day 31
1
6.7%
0
0%
0
0%
1
2.2%
Superinfection bacterial day 3
0
0%
0
0%
0
0%
0
0%
Superinfection bacterial day 7
0
0%
0
0%
0
0%
0
0%
Superinfection bacterial day 15
0
0%
0
0%
0
0%
0
0%
Superinfection bacterial day 31
0
0%
0
0%
1
6.7%
1
2.2%
Urinary tract infection day 3
0
0%
0
0%
0
0%
0
0%
Urinary tract infection day 7
0
0%
0
0%
1
6.7%
1
2.2%
Urinary tract infection day 15
0
0%
0
0%
1
6.7%
1
2.2%
Urinary tract infection day 31
0
0%
0
0%
1
6.7%
1
2.2%
C-reactive protein increased day 3
0
0%
0
0%
0
0%
0
0%
C-reactive protein increased day 7
1
6.7%
0
0%
0
0%
1
2.2%
C-reactive protein increased day 15
1
6.7%
0
0%
0
0%
1
2.2%
C-reactive protein increased day 31
1
6.7%
0
0%
0
0%
1
2.2%
Gamma-glutamyltransferase increased day 3
0
0%
1
6.7%
0
0%
1
2.2%
Gamma-glutamyltransferase increased day 7
1
6.7%
1
6.7%
0
0%
2
4.4%
Gamma-glutamyltransferase increased day 15
1
6.7%
2
13.3%
0
0%
3
6.7%
Gamma-glutamyltransferase increased day 31
1
6.7%
2
13.3%
0
0%
3
6.7%
Serum ferritin increased day 3
0
0%
0
0%
0
0%
0
0%
Serum ferritin increased day 7
1
6.7%
0
0%
0
0%
1
2.2%
Serum ferritin increased day 15
1
6.7%
0
0%
0
0%
1
2.2%
Serum ferritin increased day 31
1
6.7%
0
0%
0
0%
1
2.2%
Hyperglycaemia day 3
0
0%
0
0%
1
6.7%
1
2.2%
Hyperglycaemia day 7
0
0%
0
0%
1
6.7%
1
2.2%
Hyperglycaemia day 15
0
0%
0
0%
1
6.7%
1
2.2%
Hyperglycaemia day 31
0
0%
0
0%
1
6.7%
1
2.2%
Status epilepticus day 3
0
0%
0
0%
0
0%
0
0%
Status epilepticus day 7
0
0%
0
0%
0
0%
0
0%
Status epilepticus day 15
0
0%
0
0%
0
0%
0
0%
Status epilepticus day 31
0
0%
0
0%
1
6.7%
1
2.2%
Acute respiratory distress syndrome day 3
0
0%
0
0%
0
0%
0
0%
Acute respiratory distress syndrome day 7
1
6.7%
1
6.7%
0
0%
2
4.4%
Acute respiratory distress syndrome day 15
1
6.7%
1
6.7%
1
6.7%
3
6.7%
Acute respiratory distress syndrome day 31
2
13.3%
1
6.7%
1
6.7%
4
8.9%
Pneumomediastinum day 3
0
0%
0
0%
0
0%
0
0%
Pneumomediastinum day 7
0
0%
0
0%
0
0%
0
0%
Pneumomediastinum day 15
0
0%
0
0%
0
0%
0
0%
Pneumomediastinum day 31
0
0%
0
0%
1
6.7%
1
2.2%
Respiratory distress day 3
0
0%
0
0%
0
0%
0
0%
Respiratory distress day 7
0
0%
0
0%
1
6.7%
1
2.2%
Respiratory distress day 15
0
0%
0
0%
1
6.7%
1
2.2%
Respiratory distress day 31
0
0%
0
0%
1
6.7%
1
2.2%
11. Primary Outcome
Title Percentage of Patients in Whom Treatment Cannot be Completed.
Description Percentage of patients in whom treatment cannot be completed and the reasons.
Time Frame At 3 days from the first dose of study treatment

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Experimental 1 Experimental 2 Experimental 3 Total
Arm/Group Description Plitidepsin 1.5 mg / day x 3 consecutive days Plitidepsin 2.0 mg / day x 3 consecutive days Plitidepsin 2.5 mg / day x 3 consecutive days All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety.
Measure Participants 15 15 15 45
Count of Participants [Participants]
1
6.7%
0
0%
0
0%
1
2.2%
12. Primary Outcome
Title Percentage of Patients With Adverse Events.
Description Percentage of patients with adverse events.
Time Frame At days 3, 7, 15 and 31

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Experimental 1 Experimental 2 Experimental 3 Total
Arm/Group Description Plitidepsin 1.5 mg / day x 3 consecutive days Plitidepsin 2.0 mg / day x 3 consecutive days Plitidepsin 2.5 mg / day x 3 consecutive days All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety.
Measure Participants 15 15 15 45
Day 3
14
93.3%
11
73.3%
13
86.7%
38
84.4%
Day 7
15
100%
14
93.3%
15
100%
44
97.8%
Day 15
15
100%
14
93.3%
15
100%
44
97.8%
Day 31
15
100%
14
93.3%
15
100%
44
97.8%
13. Primary Outcome
Title Percentage of Patients With Serious Adverse Events.
Description Percentage of patients with serious adverse events.
Time Frame At days 3, 7, 15 and 31

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Experimental 1 Experimental 2 Experimental 3 Total
Arm/Group Description Plitidepsin 1.5 mg / day x 3 consecutive days Plitidepsin 2.0 mg / day x 3 consecutive days Plitidepsin 2.5 mg / day x 3 consecutive days All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety.
Measure Participants 15 15 15 45
Day 3
1
6.7%
0
0%
0
0%
1
2.2%
Day 7
4
26.7%
1
6.7%
0
0%
5
11.1%
Day 15
4
26.7%
1
6.7%
2
13.3%
7
15.6%
Day 31
6
40%
1
6.7%
3
20%
10
22.2%
14. Primary Outcome
Title Percentage of Patients With ECG Abnormalities.
Description Percentage of patients with ECG abnormalities.
Time Frame At days 2, 3, 4, 5, 6, 7, 15 and 31

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Experimental 1 Experimental 2 Experimental 3 Total
Arm/Group Description Plitidepsin 1.5 mg & day x 3 consecutive days Plitidepsin 2.0 mg & day x 3 consecutive days Plitidepsin 2.5 mg & day x 3 consecutive days All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety
Measure Participants 15 15 15 45
Day 2
2
13.3%
3
20%
3
20%
8
17.8%
Day 3
4
26.7%
2
13.3%
2
13.3%
8
17.8%
Day 4
3
20%
1
6.7%
1
6.7%
5
11.1%
Day 5
3
20%
1
6.7%
2
13.3%
6
13.3%
Day 6
4
26.7%
1
6.7%
2
13.3%
7
15.6%
Day 7
1
6.7%
1
6.7%
3
20%
5
11.1%
Day 15
2
13.3%
2
13.3%
2
13.3%
6
13.3%
Day 31
2
13.3%
0
0%
1
6.7%
3
6.7%
15. Secondary Outcome
Title Change in the Viral Load of SARS-CoV-2
Description Median change in the viral load of SARS-CoV-2 from baseline.
Time Frame At days 4, 7, 15 and 31

Outcome Measure Data

Analysis Population Description
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/Group Title Experimental 1 Experimental 2 Experimental 3 Total
Arm/Group Description Plitidepsin 1.5 mg / day x 3 consecutive days Plitidepsin 2.0 mg / day x 3 consecutive days Plitidepsin 2.5 mg / day x 3 consecutive days All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety.
Measure Participants 14 15 15 44
Day 4
-1.23
(1.30)
-1.49
(1.42)
-1.32
(1.90)
-1.35
(1.54)
Day 7
-2.55
(1.65)
-2.26
(1.68)
-2.25
(1.61)
-2.35
(1.61)
Day 15
-4.22
(2.58)
-2.70
(2.23)
-2.92
(1.91)
-3.25
(2.29)
Day 31
-4.70
(1.74)
-3.53
(2.07)
-3.49
(2.94)
-3.85
(2.35)
16. Secondary Outcome
Title Time to Negative PCR Test for COVID-19
Description Time from inclusion/randomization to date of negative PCR test for COVID-19
Time Frame Up to 31 days + 3 days for window period

Outcome Measure Data

Analysis Population Description
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/Group Title Experimental 1 Experimental 2 Experimental 3 Total
Arm/Group Description Plitidepsin 1.5 mg / day x 3 consecutive days Plitidepsin 2.0 mg / day x 3 consecutive days Plitidepsin 2.5 mg / day x 3 consecutive days All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety.
Measure Participants 14 15 15 44
Mean (Full Range) [Days]
11
14
14
13
17. Secondary Outcome
Title Mortality
Description Percentage of patients who die during the study
Time Frame At days 7, 15 and 31

Outcome Measure Data

Analysis Population Description
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/Group Title Experimental 1 Experimental 2 Experimental 3 Total
Arm/Group Description Plitidepsin 1.5 mg / day x 3 consecutive days Plitidepsin 2.0 mg / day x 3 consecutive days Plitidepsin 2.5 mg / day x 3 consecutive days All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety.
Measure Participants 14 15 15 44
Day 7
0
0%
0
0%
0
0%
0
0%
Day 15
0
0%
0
0%
0
0%
0
0%
Day 31
1
6.7%
0
0%
1
6.7%
2
4.4%
18. Secondary Outcome
Title Percentage of Patients Requiring Invasive Mechanical Ventilation and / or ICU Admission
Description Percentage of patients requiring invasive mechanical ventilation and / or ICU admission
Time Frame At days 7, 15 and 31

Outcome Measure Data

Analysis Population Description
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/Group Title Experimental 1 Experimental 2 Experimental 3 Total
Arm/Group Description Plitidepsin 1.5 mg / day x 3 consecutive days Plitidepsin 2.0 mg / day x 3 consecutive days Plitidepsin 2.5 mg / day x 3 consecutive days All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety.
Measure Participants 14 15 15 44
Day 7
2
13.3%
1
6.7%
2
13.3%
5
11.1%
Day 15
2
13.3%
1
6.7%
3
20%
6
13.3%
Day 31
2
13.3%
1
6.7%
3
20%
6
13.3%
19. Secondary Outcome
Title Percentage of Patients Requiring Non-invasive Mechanical Ventilation
Description Percentage of patients requiring non-invasive mechanical ventilation
Time Frame At days 7, 15 and 31

Outcome Measure Data

Analysis Population Description
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/Group Title Experimental 1 Experimental 2 Experimental 3 Total
Arm/Group Description Plitidepsin 1.5 mg / day x 3 consecutive days Plitidepsin 2.0 mg / day x 3 consecutive days Plitidepsin 2.5 mg / day x 3 consecutive days All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety.
Measure Participants 14 15 15 44
Day 7
4
26.7%
0
0%
1
6.7%
5
11.1%
Day 15
5
33.3%
0
0%
2
13.3%
7
15.6%
Day 31
5
33.3%
1
6.7%
2
13.3%
8
17.8%
20. Secondary Outcome
Title Percentage of Patients Requiring Oxygen Therapy
Description Percentage of patients requiring oxygen therapy
Time Frame At days 7, 15 and 31

Outcome Measure Data

Analysis Population Description
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/Group Title Experimental 1 Experimental 2 Experimental 3 Total
Arm/Group Description Plitidepsin 1.5 mg / day x 3 consecutive days Plitidepsin 2.0 mg / day x 3 consecutive days Plitidepsin 2.5 mg / day x 3 consecutive days All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety.
Measure Participants 14 15 15 44
Day 7
12
80%
12
80%
11
73.3%
35
77.8%
Day 15
12
80%
12
80%
11
73.3%
35
77.8%
Day 31
12
80%
12
80%
11
73.3%
35
77.8%

Adverse Events

Time Frame From first administration of plitidepsin until day 31.
Adverse Event Reporting Description 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.
Arm/Group Title Experimental 1 Experimental 2 Experimental 3 Total
Arm/Group Description Plitidepsin 1.5 mg / day x 3 consecutive days Plitidepsin 2.0 mg / day x 3 consecutive days Plitidepsin 2.5 mg / day x 3 consecutive days All the 45 patients treated with at least 1 dose of plitidepsin were analyzed for safety.
All Cause Mortality
Experimental 1 Experimental 2 Experimental 3 Total
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1/15 (6.7%) 0/15 (0%) 1/15 (6.7%) 2/45 (4.4%)
Serious Adverse Events
Experimental 1 Experimental 2 Experimental 3 Total
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 6/15 (40%) 1/15 (6.7%) 3/15 (20%) 10/45 (22.2%)
General disorders
Condition aggravated 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/45 (2.2%) 1
Immune system disorders
Anaphylactic reaction 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/45 (2.2%) 1
Infections and infestations
Pyelonephritis 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/45 (2.2%) 1
COVID-19 pneumonia 1/15 (6.7%) 1 0/15 (0%) 0 1/15 (6.7%) 2 2/45 (4.4%) 3
Superinfection bacterial 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 1/45 (2.2%) 1
Nervous system disorders
Status epilepticus 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 1/45 (2.2%) 1
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome 2/15 (13.3%) 3 1/15 (6.7%) 1 1/15 (6.7%) 1 4/45 (8.9%) 5
Respiratory failure 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 2 1/45 (2.2%) 2
Pneumomediastinum 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 1/45 (2.2%) 1
Other (Not Including Serious) Adverse Events
Experimental 1 Experimental 2 Experimental 3 Total
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 15/15 (100%) 14/15 (93.3%) 15/15 (100%) 44/45 (97.8%)
Blood and lymphatic system disorders
Anaemia 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 2 1/45 (2.2%) 2
Leukocytosis 0/15 (0%) 0 0/15 (0%) 0 3/15 (20%) 3 3/45 (6.7%) 3
Lymphopenia 1/15 (6.7%) 3 1/15 (6.7%) 1 1/15 (6.7%) 1 3/45 (6.7%) 5
Neutrophilia 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 1/45 (2.2%) 1
Cardiac disorders
Atrial fibrillation 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 2 1/45 (2.2%) 2
Tachycardia 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 1/45 (2.2%) 1
Ear and labyrinth disorders
Vertigo 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 1/45 (2.2%) 1
Gastrointestinal disorders
Abdominal pain 2/15 (13.3%) 2 0/15 (0%) 0 2/15 (13.3%) 2 4/45 (8.9%) 4
Constipation 4/15 (26.7%) 4 2/15 (13.3%) 2 2/15 (13.3%) 2 8/45 (17.8%) 8
Diarrhoea 1/15 (6.7%) 1 4/15 (26.7%) 6 3/15 (20%) 3 8/45 (17.8%) 10
Dyspepsia 2/15 (13.3%) 2 1/15 (6.7%) 1 1/15 (6.7%) 1 4/45 (8.9%) 4
Nausea 6/15 (40%) 9 6/15 (40%) 7 7/15 (46.7%) 9 19/45 (42.2%) 25
Rectal haemorrhage 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 1/45 (2.2%) 1
Vomiting 0/15 (0%) 0 4/15 (26.7%) 5 4/15 (26.7%) 7 8/45 (17.8%) 12
General disorders
Asthenia 3/15 (20%) 4 1/15 (6.7%) 3 2/15 (13.3%) 3 6/45 (13.3%) 10
Chest discomfort 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 1/45 (2.2%) 1
Pyrexia 8/15 (53.3%) 10 5/15 (33.3%) 12 7/15 (46.7%) 17 20/45 (44.4%) 39
Malaise 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/45 (2.2%) 1
Temperature regulation disorder 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 1/45 (2.2%) 1
Fatigue 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 1/45 (2.2%) 1
Hepatobiliary disorders
Hypoalbuminaemia 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 1/45 (2.2%) 1
Infections and infestations
Bacteremia 0/15 (0%) 0 1/15 (6.7%) 1 1/15 (6.7%) 1 2/45 (4.4%) 2
COVID-19 pneumonia 2/15 (13.3%) 2 0/15 (0%) 0 0/15 (0%) 0 2/45 (4.4%) 2
Pneumonia 1/15 (6.7%) 1 1/15 (6.7%) 1 0/15 (0%) 0 2/45 (4.4%) 2
Skin candida 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/45 (2.2%) 1
Urinary tract infection 0/15 (0%) 0 0/15 (0%) 0 2/15 (13.3%) 2 2/45 (4.4%) 2
Viral infection 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 1/45 (2.2%) 1
Injury, poisoning and procedural complications
Fall 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 1/45 (2.2%) 1
Investigations
Alkaline phosphatase increased 1/15 (6.7%) 1 1/15 (6.7%) 1 0/15 (0%) 0 2/45 (4.4%) 2
ALT increased 2/15 (13.3%) 4 1/15 (6.7%) 3 2/15 (13.3%) 2 5/45 (11.1%) 9
Amylase increased 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 1/45 (2.2%) 1
AST increased 1/15 (6.7%) 2 1/15 (6.7%) 2 1/15 (6.7%) 1 3/45 (6.7%) 5
Blood cholesterol increased 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 1/45 (2.2%) 1
Blood creatinine increased 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 1/45 (2.2%) 1
Blood fibrinogen increased 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 2 1/45 (2.2%) 2
Blood glucose increased 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 1/45 (2.2%) 1
CPK increased 0/15 (0%) 0 2/15 (13.3%) 2 0/15 (0%) 0 2/45 (4.4%) 2
C-reactive protein increased 4/15 (26.7%) 8 4/15 (26.7%) 4 3/15 (20%) 4 11/45 (24.4%) 16
Ferritin increased 5/15 (33.3%) 11 4/15 (26.7%) 6 5/15 (33.3%) 5 14/45 (31.1%) 22
GGT increased 3/15 (20%) 8 2/15 (13.3%) 5 1/15 (6.7%) 1 6/45 (13.3%) 14
LDH increased 1/15 (6.7%) 1 1/15 (6.7%) 1 2/15 (13.3%) 2 4/45 (8.9%) 4
LDL increased 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/45 (2.2%) 1
Oxygen saturation decreased 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/45 (2.2%) 1
Transaminases increased 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/45 (2.2%) 1
Triglycerides increased 1/15 (6.7%) 1 1/15 (6.7%) 1 0/15 (0%) 0 2/45 (4.4%) 2
Fibrin D dimer increased 3/15 (20%) 5 2/15 (13.3%) 3 3/15 (20%) 3 8/45 (17.8%) 11
Platelet count decreased 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 1/45 (2.2%) 1
Neutrophil count increased 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 1/45 (2.2%) 1
Interleukin level increased 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 1/45 (2.2%) 1
Lipase increased 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 1/45 (2.2%) 1
Metabolism and nutrition disorders
Decreased appetite 1/15 (6.7%) 2 1/15 (6.7%) 2 0/15 (0%) 0 2/45 (4.4%) 4
Dehydration 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/45 (2.2%) 1
Hyponatraemia 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/45 (2.2%) 1
Hyperglycaemia 3/15 (20%) 3 2/15 (13.3%) 3 3/15 (20%) 7 8/45 (17.8%) 13
Hyperkalaemia 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 1/45 (2.2%) 1
Malnutrition 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 1/45 (2.2%) 1
Musculoskeletal and connective tissue disorders
Arthralgia 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/45 (2.2%) 1
Back pain 0/15 (0%) 0 1/15 (6.7%) 1 1/15 (6.7%) 1 2/45 (4.4%) 2
Muscular weakness 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/45 (2.2%) 1
Myalgia 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 1/45 (2.2%) 1
Tenosynovitis 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/45 (2.2%) 1
Nervous system disorders
Dizziness 1/15 (6.7%) 1 0/15 (0%) 0 2/15 (13.3%) 3 3/45 (6.7%) 4
Dysgeusia 0/15 (0%) 0 0/15 (0%) 0 2/15 (13.3%) 4 2/45 (4.4%) 4
Headache 4/15 (26.7%) 5 2/15 (13.3%) 3 0/15 (0%) 0 6/45 (13.3%) 8
Insomnia 2/15 (13.3%) 3 2/15 (13.3%) 2 0/15 (0%) 0 4/45 (8.9%) 5
Migraine 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 1/45 (2.2%) 1
Paraesthesia 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/45 (2.2%) 1
Presyncope 3/15 (20%) 3 1/15 (6.7%) 1 0/15 (0%) 0 4/45 (8.9%) 4
Somnolence 0/15 (0%) 0 1/15 (6.7%) 1 1/15 (6.7%) 1 2/45 (4.4%) 2
Psychiatric disorders
Agitation 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 1/45 (2.2%) 1
Anxiety 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/45 (2.2%) 1
Delirium 0/15 (0%) 0 1/15 (6.7%) 1 1/15 (6.7%) 1 2/45 (4.4%) 2
Renal and urinary disorders
Pollakiuria 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/45 (2.2%) 1
Prerenal failure 1/15 (6.7%) 1 0/15 (0%) 0 1/15 (6.7%) 1 2/45 (4.4%) 2
Renal impairment 0/15 (0%) 0 0/15 (0%) 0 2/15 (13.3%) 2 2/45 (4.4%) 2
Reproductive system and breast disorders
Breast engorgement 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 1/45 (2.2%) 1
Respiratory, thoracic and mediastinal disorders
Respiratory failure 1/15 (6.7%) 2 0/15 (0%) 0 1/15 (6.7%) 1 2/45 (4.4%) 3
Chest discomfort 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 1/45 (2.2%) 1
Cough 4/15 (26.7%) 4 3/15 (20%) 3 4/15 (26.7%) 5 11/45 (24.4%) 12
Dyspnoea 3/15 (20%) 3 2/15 (13.3%) 2 2/15 (13.3%) 2 7/45 (15.6%) 7
Hypoxia 0/15 (0%) 0 1/15 (6.7%) 1 1/15 (6.7%) 3 2/45 (4.4%) 4
Productive cough 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 1/45 (2.2%) 1
Respiratory distress 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 1 1/45 (2.2%) 1
Tachypnoea 1/15 (6.7%) 1 1/15 (6.7%) 1 0/15 (0%) 0 2/45 (4.4%) 2
Interstitial lung disease 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/45 (2.2%) 1
Pleuritic pain 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/45 (2.2%) 1
Pneumothorax spontaneous 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/45 (2.2%) 1
Skin and subcutaneous tissue disorders
Skin ulcer 0/15 (0%) 0 1/15 (6.7%) 1 0/15 (0%) 0 1/45 (2.2%) 1
Vascular disorders
Hypertension 0/15 (0%) 0 0/15 (0%) 0 2/15 (13.3%) 2 2/45 (4.4%) 2
Hypotension 0/15 (0%) 0 0/15 (0%) 0 1/15 (6.7%) 2 1/45 (2.2%) 2
Phlebitis 3/15 (20%) 3 3/15 (20%) 5 2/15 (13.3%) 2 8/45 (17.8%) 10
Thrombophlebitis 1/15 (6.7%) 1 0/15 (0%) 0 0/15 (0%) 0 1/45 (2.2%) 1

Limitations/Caveats

Small number of patients. No control group.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

Results Point of Contact

Name/Title Clinical Development Virology Business Unit PharmaMar
Organization PharmaMar, S.A.
Phone +34 91 846 60 00
Email clinicaltrials@pharmamar.com
Responsible Party:
PharmaMar
ClinicalTrials.gov Identifier:
NCT04382066
Other Study ID Numbers:
  • APL-D-002-20
  • 2020-001993-31
First Posted:
May 11, 2020
Last Update Posted:
Aug 23, 2022
Last Verified:
Jul 1, 2022