Trial to Determine the Efficacy/Safety of Plitidepsin vs Control in Patients With Moderate COVID-19 Infection

• Status: Recruiting
• Trial end date: 2022-03-01
• Target enrollment: 0
• Participant gender: All

Summary

Treatment of patients hospitalised for management of moderate COVID-19 infection

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: PharmaMar
• Treatments: Dexamethasone; Favipiravir; Remdesivir

Criteria

Inclusion Criteria:

1. Signed informed consent obtained prior to initiation of any study-specific procedures and study treatment

2. Documented diagnosis of SARS-CoV-2 infection, determined by either qualitative polymerase chain reaction (PCR) or antigen test by local laboratory, from oro nasopharyngeal exudate collected no more than 72 hours prior to study treatment on Day 1

3. Patient meets category 5 on the 11-point WHO Clinical Progression Scale: requires hospitalization and oxygen by mask or nasal prongs/cannula

4. A maximum of 10 days from onset of COVID-19 symptoms to initiation of study treatment on Day 1

5. Male or female aged ≥18 years

6. Adequate bone marrow, liver, kidney, and metabolic function, defined by the following tests performed at local laboratory:

• Absolute neutrophil count ≥1000/mm^3 (1.0 x 10^9/L)

• Lymphocyte count ≥500/mm^3 (0.5 x 10^9/L)

• Platelet count ≥100 000/mm^3 (100 x 10^9/L)

• Haemoglobin >9.0 g/dL

• Alanine transaminase (ALT), aspartate transaminase (AST) ≤3 x upper limit of normal (ULN)

• Serum bilirubin ≤1 x ULN

• Calculated creatinine clearance ≥30 mL/min (Cockcroft and Gault formula)

• Creatine phosphokinase ≤2.5 x ULN except if the patient has had recent (ie, in the last week) shivering episodes or trauma. In that case, the level of creatine phosphokinase (CPK) should be ≤5 x ULN).

7. Agree not to participate in another interventional clinical trial through Day 31

8. Females of reproductive capacity must have a negative serum or urine pregnancy test by local laboratory at study enrolment and must be non-lactating

9. Females and males with partners of child-bearing potential must use effective contraception while on study treatment and for 6 months after last dose of plitidepsin. Patients in the control arm must use effective contraception at the time indicated in the approved product information (summary of product characteristics [SmPC] or leaflet). If no information is available in the approved product information, patients in the control arm must use effective contraception for at least one week after the study completion or the time indicated based on the investigator's discretion.

Exclusion Criteria:

1. Subjects with a pre-baseline (ie, in the prior month) impairment in general health condition for whatever reason except COVID 19, requiring either assistance for daily living activities (Barthel index <90/100) or chronic oxygen therapy

2. Having received treatment for COVID 19 in another clinical trial in the prior 4 weeks, except documented allocation in a placebo arm.

3. Evidence of respiratory failure at the time of randomisation, based on resource utilisation requiring at least one of the following: endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula, noninvasive positive pressure ventilation, ECMO, or clinical diagnosis of respiratory failure (ie, clinical need for one of the preceding therapies, but preceding therapies not able to be administered in setting of resource limitation)

4. Patients with severe COVID 19, meeting score >5 on the 11 point WHO Clinical Progression Scale or presenting during the screening any of clinical signs indicative of severe systemic illness, such as respiratory rate ≥30 per minute, heart rate ≥125 per minute, or PaO2/FiO2 <300

5. Patients receiving treatment with antiviral therapy against SARS-CoV-2 (either small molecules or antibodies, convalescent plasma, monoclonal antibodies, IL 6 receptor inhibitor, or immunomodulatory drugs) within 2 weeks before enrolment. Prior administration of dexamethasone or equivalent glucocorticoid might be acceptable if:

1. The total daily dose is not higher than 6 mg of dexamethasone base (equivalent to dexamethasone phosphate 7.2 mg/day) or equivalent glucocorticoid

2. The duration of the treatment does not exceed 72 hours prior to study treatment Day 1

6. History of live vaccination within the last 4 weeks prior to study enrolment. Regulatory approved, nonreplicative viral vector based vaccines are allowed if given not earlier than 1 week previous to Day 1.

7. Patients receiving treatment with chloroquine or derivatives within 8 weeks before enrolment or during the study

8. Patients receiving treatment with strong cytochrome P450 3A4 ( CYP3A4) inhibitors or inducers

9. Viral illness (other than COVID 19) requiring therapy, except for patients with treated and adequately controlled (undetectable) human immunodeficiency virus infection

10. Patients with uncontrolled known primary or secondary immunodeficiency, including chronic treatment with glucocorticoids (ie, prednisone at a daily dose of >10 mg for >1 month, or other glucocorticoid at equipotent dose)

11. Any of the following cardiac conditions or risk factors:

• 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;

• Known abnormal value of left ventricular ejection fraction (LVEF < LLN), unless documented confirmation of recovery (LVEF > LLN) in the previous month;

• QT interval corrected using Fridericia's formula (QTcF) >450 msec for males or >470 msec for females, based on triplicate 12-lead ECG at screening

• History of known congenital or acquired QT prolongation

• Uncorrected hypokalaemia, hypocalcaemia (adjusted), and/or hypomagnesemia at screening

• Concomitant treatments with drugs known to be associated with a risk of QT prolongation or cardiac arrhythmia

• Troponin test performed at local laboratory > 1.5 x ULN

12. Pre-existing neuropathies of any type Grade ≥2 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0

13. Hypersensitivity to the active ingredient or any of the excipients (mannitol, macrogolglycerol hydroxystearate, and ethanol)

14. Females who are pregnant (negative serum or urine pregnancy test required for all females of child-bearing potential at screening) or breast feeding

15. Females and males with partners of child-bearing potential (females who are not surgically sterile or postmenopausal defined as amenorrhoea for >12 months) who are not using at least 1 protocol-specified method of contraception

16. Any other clinically significant medical condition or laboratory abnormality that, in the opinion of the investigator, would jeopardise the safety of the patient or potentially impact patient compliance or the safety/efficacy observations in the study.