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

  • End date
    Nov 19, 2021
  • participants needed
  • sponsor
Updated on 28 July 2021


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


This is a multicentre, open-label, controlled Phase 3 study in which adults requiring hospital admission and O2 supplementation for management of moderate COVID-19 infection will be randomised in 1:1:1 to: Plitidepsin 1.5 mg arm, Plitidepsin 2.5 mg arm and Control arm

Condition Covid 19 Infection
Treatment Dexamethasone, Plitidepsin, Remdesivir
Clinical Study IdentifierNCT04784559
Last Modified on28 July 2021


Yes No Not Sure

Inclusion Criteria

Signed informed consent obtained prior to initiation of any study-specific procedures and study treatment
Laboratory confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as determined by qualitative polymerase chain reaction (PCR) by local laboratory from oro/nasopharyngeal exudate (or other respiratory specimen) collected no more than 24 hours prior to study treatment on Day 1
Admitted to hospital as clinically indicated for management of moderate SARS-CoV-2 (COVID-19) infection, defined by the following criteria
Positive PCR test for SARS-CoV-2
Symptoms of moderate illness with COVID-19, which could include any symptoms of mild illness or shortness of breath with exertion
Clinical signs suggestive of moderate illness with COVID-19 such as respiratory rate 20 but <30 breaths per minute, saturation of oxygen (SpO2) >93% but <95% on room air at sea level, heart rate 90 but <125 beats per minute, and requiring O2 supplementation. If SpO2 on room air is not possible to be measured, the ratio partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) should be 300 mm Hg; in addition, if the site is located at high altitude over sea level (> 1000 m), the ratio PaO2/FiO2 should be adjusted
No clinical signs indicative of severe illness, which could include shortness of breath at rest or respiratory distress, or PaO2/FiO2 ratio < 300 mm Hg (sea level)
Onset of COVID-19 symptoms no later than 6 days prior to initiation of study treatment on Day 1
Male or female aged 18 years
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
Agree not to participate in another interventional clinical trial through Day 31
Females of reproductive capacity must have a negative serum pregnancy test by local laboratory at study enrolment and must be non-lactating
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

Exclusion Criteria

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 or chronic oxygen therapy
Participating in another clinical trial for treatment of COVID 19 infection or patients previously enrolled in clinical trials and currently in follow up, or patients previously vaccinated for COVID 19
Evidence of respiratory failure at the time of randomisation, based on resource utilisation requiring at least 1 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 1 of the preceding therapies, but preceding therapies not able to be administered in setting of resource limitation)
Patients clinically indicated for management of SARS CoV 2 (COVID 19), with baseline disease severity rated as severe (if positive testing by standard reverse transcription polymerase chain reaction (RT-PCR) assay or equivalent test, symptoms suggestive of severe illness with COVID 19, which could include any symptom of moderate illness or shortness of breath at rest, or respiratory distress, clinical signs indicative of severe systemic illness with COVID 19, such as respiratory rate 30 per minute, heart rate 125 per minute, SpO2 93% on room air at sea level, or PaO2/FiO2 <300)
Patients receiving treatment with antivirals, interleukin (IL) 6 receptor inhibitor, corticosteroids, or immunomodulatory drugs for COVID 19 infection within 4 weeks before enrolment
History of live vaccination within the last 4 weeks prior to study enrolment; subjects must not receive live, attenuated influenza vaccine within 4 weeks before enrolment or at any time during the study
Patients receiving treatment with chloroquine or derivatives within 8 weeks before enrolment or during the study
Receiving treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers (see Appendix 4)
Viral illness (other than COVID 19) requiring therapy, except for patients with treated and adequately controlled (undetectable) human immunodeficiency virus infection are eligible
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 ECG at screening
History of known congenital or acquired QT prolongation
Uncorrected hypokalaemia, hypoglycaemia (adjusted) and/or hypomagnesemia at baseline
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
Pre-existing neuropathies of any type Grade 2
Hypersensitivity to the active ingredient or any of the excipients (mannitol, macrogolglycerol hydroxystearate, and ethanol)
Females who are pregnant (negative serum pregnancy test required for all females of child-bearing potential at screening) or breast feeding
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
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
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