U07.1 COVID-19, virus COVID-19, virus
Conditions
Interventions
Patients will receive plitidepsin 1.5 mg/day intravenous (IV) combined with dexamethasone phosphate 8 mg/day (equivalent to 6.6 mg of dexamethasone base) IV on Days 1 to 3, followed by dexamethasone p
Sponsors
Pharma Mar S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Signed informed consent obtained prior to initiation of any study-specific procedures and study treatment 2. Laboratory confirmed 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 3. 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 e 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 breaths but 93% but = 300 mm Hg (see Appendix 9); in addition, if the site is located at high altitude over sea level (> 1000 m), the ratio PaO2/FiO2 should be adjusted ( Appendix 10) • No clinical signs indicative of severe illness, which could include shortness of breath at rest or respiratory distress, or PaO2/FiO2 ratio 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 7. Agree not to participate in another interventional clinical trial through Day 31 8. Females of reproductive capacity must have a negative serum 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.
Exclusion criteria
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 or chronic oxygen therapy 2. 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 3. 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) 4. Patients clinically indicated for management of SARS-CoV-2 (COVID-19), with baseline disease severity rated as severe (if positive testing by standard 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 200 msec), or any other bradyarrhthymia ( 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 hypokaliemia, hypocalcemia (adjusted) and/or hypomagnesemia at baseline; • Concomitant treatments with drugs known to be associated with a risk of QT prolongation or cardiac arrhythmia (Appendix 8a); or • Baseline troponin > 1.5 x ULN. 11. Pre-existing neuropathies of any type Grade =2 12. Hypersensitivity to the active ingredient or any of the excipients (mannitol, macrogolglycerol hydroxys
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Compare plitidepsin 1.5 or 2.5 mg versus control on the percentage of patients who achieve complete recovery by Day 8 (±1), defined as (i) meeting categories 0 to 2 on the 11- point WHO Clinical Progression Scale below, (ii) having Barthel Index >90/100 at the time of discharge (Appendix 7), and (iii) with no re-admission for COVID-19 signs or symptoms through Day 31. NAME OF THE RESULT: Efficacy PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Day 8 (±1) | — |
Secondary
| Measure | Time frame |
|---|---|
| Compare plitidepsin 1.5 or 2.5 mg versus control on the percentage of patients who achieve complete recovery by Day 8 (±1), defined as (i) meeting categories 0 to 2 on the 11- point WHO Clinical Progression Scale below, (ii) having Barthel Index >90/100 at the time of discharge (Appendix 7), and (iii) with no re-admission for COVID-19 signs or symptoms through Day 31. NAME OF THE RESULT: Efficacy PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Day 8 (±1) ;Clinical status, as assessed by the 11-category WHO Clinical Progression Scale, at Day 8 (±1) NAME OF THE RESULT: Efficacy PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Day 8 (±1) ;• Incidence of TEAEs, Grade =3 TEAEs, SAEs, deaths, and TEAEs leading to premature discontinuation of study drug. • Change from baseline in clinical laboratory results • Change from baseline in vital signs results • Change from baseline in ECG findings NAME OF THE RESULT: Safety PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From treatment initiation on Day 1, patients will be followed in the hospital for at least 4 days and then through Day 31 or resolution/stabilisation of TEAEs that occurred through Day 31. | — |
Countries
Argentina, Brazil, Bulgaria, Colombia, France, Greece, Mexico, Romania, Spain, United Kindgdom
Contacts
Public ContactFlor de Liz Jacome
LABCORP PERU SERVICES S.A.
Outcome results
None listed