Study to Evaluate the Viral Load Reduction of a Single Dose of Plitidepsin in Adult Patients With COVID-19

Lead Sponsor: PharmaMar

Collaborator: Apices Soluciones S.L.

The main objective of this study is to evaluate the efficacy and safety of a single dose of plitidepsin in order to reduce the viral load and symptoms recovery after discharge from Emergency.

More than a year after the appearance of the new SARS-COV-2 coronavirus, the search continues for an effective treatment to reduce the symptoms and infectivity of a pandemic that has left behind more than 120 million cases and more than 2.5 million deaths. Plitidepsin is an approved multiple myeloma drug in Australia that in both preclinical and clinical studies has shown a clear antiviral effect against SARS.COV-2 and, in this study, we propose to evaluate the efficacy of a single dose of plitidepsin 7.5 mg administered in 90 minutes through decreasing viral load at day 6 and symptoms recovery at day 14 with after the patient is discharged from Emergency.

• COVID-19

Intervention Type: Drug

Intervention Name: Plitidepsin

Description: Single dose of 7.5 mg plitidepsin administered as a 90-minute infusion (±10 minutes) plus symptomatic treatment according clinical practice: If muscular pain, arthralgia, and fever > 38ºC: Paracetamol 1 g/8 hours 7-10 days. If symptoms persist: Metamizole 500 mg /8 hours. If diarrea of > 10 stools: Loperamide as per SmPC.

Arm Group Label: Plitidepsin plus symptomatic treatment

Intervention Type: Drug

Intervention Name: Symptomatic Treatment

Description: Symptomatic treatment according clinical practice: If muscular pain, arthralgia, and fever > 38ºC: Paracetamol 1 g/8 hours 7-10 days. If symptoms persist: Metamizole 500 mg /8 hours. If diarrea of > 10 stools: Loperamide as per SmPC.

Arm Group Label: Symptomatic treatment

Criteria:

Inclusion Criteria: 1. Patient who agrees to participate in the study by signing the informed consent. 2. Men and women aged ≥18 years and <80 years 3. Acute COVID-19 infection (onset of symptoms within the previous 5 days), diagnosed at emergency visit confirmed by 1. Positive antigen test for SARS COV2, or 2. PCR-RT test obtained on nasopharyngeal swab or by antigen test. positive for SARS COV2. 4. Clinically stable patient defined as: 1. Heart rate < 100 beats per minute 2. Respiratory rate < 24 breaths per minute. 3. Axillary temperature < 37.2 ºC 4. Systolic blood pressure >90 mmHg 5. SaO2 >92%. 6. Adequate level of consciousness 5. Patient without radiological criteria of severity: without radiological lung disease or with mild pneumonia confirmed by chest X-ray and without signs of severity (SaO2 ambient air >92%. FINE criteria ≤3). 6. Men and women with reproductive capacity must agree to use highly effective contraceptive methods during their participation in the study and in the 6 months following the administration of plitidepsin. 7. 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 requiring hospital admission. 3. Patients with evidence of pneumonia on recent imaging within the previous 24 hours, with respiratory failure (PO2<60 or SatO2 <92), and with a FINE score > 3. 4. Patient without analytical stability: 1. Haemoglobin < 9 g/dL. 2. Neutrophils < 1000/mm3. 3. Platelets < 100,000/mm3. 4. Lymphopenia < 800/μL. 5. GOT / GPT > 3 X ULN. 6. Bilirubin > 1 X ULN. 7. CPK > 2.5 X ULN. 8. Creatinine clearance < 30 ml/min. 9. BUN > 20 mg/dl. 10. Troponin elevation > 1.5 x ULN. 5. Patients who will not receive the vaccine for at least 30 days following emergency discharge. 6. Patients who are receiving or have received treatment with chloroquine and derivatives in the previous 50 days. 7. Patients living in an isochrone of more than 30 minutes by car, which precludes follow-up at home and the collection of the necessary samples at repeated visits. 8. Patients for whom it is foreseen that follow-up is not going to be possible for any reason (absence from home, inability to open the door at the request, etc.). 9. Patients with any known alteration of immunity including current treatment with corticoids, or with monoclonal antibody or any drug that alters the patient's immunity. 10. Clinically relevant heart disease (NYHA >2). 11. Relevant electrocardiographic abnormalities: - Sinus bradycardia (<50 beats/min), sinus nodal dysfunction (sick sinus disease), atrioventricular block of any degree (PR >200 msec), or any other bradyarrhythmia (<50 beats/min), except for patients with permanent pacemakers; - Cardiac infarction, cardiac surgery or cardiac insufficiency episode within the last 6 months; or - QT interval corrected using Fridericia's formula (QTcF) prolongation >450 msec for males or >470 msec for females, based on triplicate ECG at screening. 12. Hypersensitivity to the active substance or to any of its excipients (macrogol glycerol ricinoleate and ethanol). 13. Patients requiring or being treated with potent CYP3A4 inhibitors and inducers. 14. Patients with pulmonary thromboembolism or deep vein thrombosis, who would require new treatment with anticoagulants, which could interfere with study results by including an accepted COVID treatment in one of the arms. 15. Patients who for any reason should not be included in the study according to the evaluation of the research team.

Gender:

All

Minimum Age:

18 Years

Maximum Age:

80 Years

Healthy Volunteers:

No

Spain

2021-03-01

Type: Sponsor

• Plitidepsin
• COVID-19
• PCR

Label: Plitidepsin plus symptomatic treatment

Type: Experimental

Description: Plitidepsin 7.5 mg plus paracetamol, metamizole, and loperamide if applicable

Label: Symptomatic treatment

Type: Active Comparator

Description: Paracetamol, metamizole, and loperamide if applicable

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Treatment

Masking: None (Open Label)