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

COVID-19 Clinical Trial

— APLIDURG  

Official title:

Open Label, Randomized Phase II Study to Evaluate the Viral Load Reduction of a Single Administration of Plitidepsin in Adult Patients With COVID-19 at Discharge From Emergency

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04819919
• Other study ID #: APL-D-005-21 / APLIDURG
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: April 15, 2021
• Est. completion date: October 15, 2021

Study information

• Verified date: March 2021
• Source: PharmaMar
• Contact: Belén Sopesen Veramendi
• Phone: + 34 91 44 44 500
• Email: bsopesen[@]pharmamar.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 122
• Est. completion date: October 15, 2021
• Est. primary completion date: October 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Plitidepsin
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.
• Symptomatic Treatment
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.

Locations

Country	Name	City	State
Spain	Hospital Univeristario Infanta Leonor	Madrid
Spain	Hospital Univeristario La Paz	Madrid	Madrid N
Spain	Hospital Universitario Clínico San Carlos	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid

Sponsors (2)

Lead Sponsor	Collaborator
PharmaMar	Apices Soluciones S.L.

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in viral load and symptoms recovery (both must be met in order to achieve the objective)	Percentage of patients who achieved a reduction of viral load of <1090 copies/ml at day 6 and who move from WHO clinical progression scale score 2 or 3 to score 0 at day 14 (both must be met in order to achieve the objective)	Day 6 and 14
Secondary	Change in viral load	Difference in SARS-CoV-2 viral load from baseline	Days 4, 6 and 14
Secondary	Symptoms recovery	Percentage of patients who move from WHO clinical progression scale score 2 or 3 to score 0 at day 14.	Day 14
Secondary	Time to reduce viral load	Time to reduction of SARS-CoV-2 viral load by PCR-RT above 33 cycles.	Since baseline until day 14
Secondary	Progression to hospitalisation	Percentage of patients requiring hospital admission	3 months
Secondary	Need for ICU admission	Percentage of patients requiring ICU admission and/or invasive mechanical ventilation	3 months
Secondary	Mortalitiy assesment	Percentage of patients who death in the following 3 months after plitidepsin administration.	3 months
Secondary	Development of sequels	Percentage of patients who develop sequelae related to persistent disease.	3 months
Secondary	Normalization of analytical parameters	Percentage of patients with normalisation of laboratory parameters	Day 6
Secondary	Normalization of clinical criteria	Percentage of patients with recovery of symptoms	Day 4, 6 and 14
Secondary	Frequency of occurrence of adverse events	Frequency of occurrence of adverse events according to NCI-CTCAE v5.0 criteria.	1 month