Phase 1
Completed N=45
Proof of Concept Study to Evaluate the Safety Profile of Plitidepsin in Patients With COVID-19
Source: ClinicalTrials.gov NCT04382066 ↗Enrolled (actual)
45
Serious AEs
22.2%
Results posted
Sep 2021
Primary outcomePrimary: Frequency of Occurrence of Neutropenia ≥ Grade 3 — 0; 0; 0; 0 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Frequency of Occurrence of Neutropenia ≥ Grade 3 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Frequency of Occurrence of Thrombocytopenia ≥ Grade 3 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Frequency of Occurrence of Anemia ≥ Grade 3 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Frequency of Occurrence of Lymphopenia ≥ Grade 3 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Frequency of Occurrence of CPK Increase ≥ Grade 3 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Frequency of Occurrence of Increase Total Bilirubin or Direct Bilirubin ≥ Grade 3 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Frequency of Occurrence of Neurotoxicity ≥ Grade 3 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Frequency of Occurrence of QT-QTc Interval Extension ≥ Grade 3 |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Frequency of Occurrence of Other Adverse Events ≥ Grade 3 |
0; 0; 1; 1; 0; 0 | — |
| PRIMARY Percentage of Patients in Whom Treatment Cannot be Completed. |
1; 0; 0; 1 | — |
| PRIMARY Percentage of Patients With Adverse Events. |
14; 11; 13; 38; 15; 14 | — |
| PRIMARY Percentage of Patients With Serious Adverse Events. |
1; 0; 0; 1; 4; 1 | — |
| PRIMARY Percentage of Patients With ECG Abnormalities. |
2; 3; 3; 8; 4; 2 | — |
| SECONDARY Change in the Viral Load of SARS-CoV-2 |
-1.23; -1.49; -1.32; -1.35; -2.55; -2.26 | — |
| SECONDARY Time to Negative PCR Test for COVID-19 |
11; 14; 14; 13 | — |
| SECONDARY Mortality |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Patients Requiring Invasive Mechanical Ventilation and / or ICU Admission |
2; 1; 2; 5; 2; 1 | — |
| SECONDARY Percentage of Patients Requiring Non-invasive Mechanical Ventilation |
4; 0; 1; 5; 5; 0 | — |
| SECONDARY Percentage of Patients Requiring Oxygen Therapy |
12; 12; 11; 35; 12; 12 | — |
Eligibility Criteria
Inclusion Criteria
- Patient who agrees to participate in the study by signing the informed consent.
- Men and women (non-pregnant) aged ≥18 years.
- COVID-19 infection confirmed by PCR obtained from nasopharyngeal exudate or sample from the lower respiratory tract.
- Patients who require hospitalization for COVID-19.
- Symptom onset at most within 10 days prior to study inclusion.
- 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.
- In addition, women participating in the study with reproductive ability must have a negative pregnancy test at enrollment.
Exclusion Criteria
- Patients participating in some other clinical trial for COVID-19 infection.
- Patients who are receiving treatment with antivirals, interleukin 6 receptor inhibitors or immunomodulatory drugs for COVID-19.
- Patients who are receiving treatment with chloroquine and derivatives.
- Evidence of multi-organ failure.
- Patients who require support with mechanical ventilation (invasive or non-invasive) at the time of inclusion.
- D-dimer> 4 x UNL.
- Hb 3 X UNL.
- Bilirubin> 1 X UNL.
- CPK> 2.5 X UNL.
- Creatinine clearance 1.5 x ULN.
- Clinically relevant heart disease (NYHA> 2).
- Clinically relevant arrhythmia or previous history / presence of prolonged QT-QTc ≥ 450 ms.
- Pre-existing neuropathies of any type ≥ grade 2.
- Hypersensitivity to the active substance or to any of its excipients (macrogol glycerol ricinoleate and ethanol).
- Patients who require or are being treated with potent CYP3A4 inhibitors and inducers.
- Patients who for any reason should not be included in the study according to the evaluation of the research team.
Data sourced from ClinicalTrials.gov (NCT04382066). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.