moderate COVID-19 infection MedDRA version: 23.0 Level: LLT Classification code 10084272 Term: SARS-CoV-2 infection System Organ Class: 100000004862
Conditions
Interventions
Product Name: plitidepsin
Product Code: SAPL01
Pharmaceutical Form: Lyophilisate for solution for infusion
INN or Proposed INN: plitidepsin
CAS Number: 137219-37-5
Current Sponsor code: SAPL01
Other d
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 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; 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 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. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 433 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 176
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 hypokalaemia, hypocalcaemia (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 - Troponin test performed at local laboratory > 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 hydroxystearate, and ethanol). 13. Females who are pregnant (negative serum pregnancy test required for all females of child-bearing p
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Comparing plitidepsin 1.5 or 2.5 mg vs 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, (iii) with no re-admission for COVID-19 signs and symptoms through Day31 0: uninfected, no viral RNA detected 1: asymptomatic, viral RNA detected 2: symptomatic, independent 3: symptomatic, assistance needed 4: hospitalised, no oxygen therapy (if hospitalised for isolation only, record status as for ambulatory patient) 5: hospitalised, oxygen by mask or nasal prongs 6: hospitalised, oxygen by noninvasive ventilation (NIV) or high flow 7: intubation and mechanical ventilation. pO2/FIO2 =150 or SpO2/FIO2 =200 8: mechanical ventilation pO2/FIO2 90/100 at the time of discharge, and (iii) has no subsequent re-admission for COVID-19 signs and symptoms *Clinical status, as assessed by the 11-category WHO Clinical Progression Scale, at Day 8 (±1);Primary end point(s): 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, and (iii) with no re-admission for COVID-19 signs and symptoms through Day 31. 0. uninfected, no viral RNA detected 1. asymptomatic, viral RNA detected 2. symptomatic, independent 3. symptomatic, assistance needed 4. hospitalised, no oxygen therapy (if hospitalised for isolation only, record status as for ambulatory patient) 5. hospitalised, oxygen by mask or nasal prongs 6. hospitalised, oxygen by NIV or high flow 7. intubation and mechanical ventilation. pO2/FIO2 =150 or SpO2/FIO2 =200 8. mechanical ventilation pO2/FIO2 <150 (SpO2/FIO2 <200) or vasopressors 9. mechanical ventilation pO2/FIO2 <150 and vasopressors, dialysis, or ECMO 10. dead;Timepo | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary objectives of this study are to compare plitidepsin 1.5 and 2.5 mg versus control on the following: • Time to complete recovery (in days), defined as the first day, from Day 1 through follow-up on Day 31, on which a patient (i) satisfies categories 0 to 2 on the 11-point WHO Clinical Progression Scale above, (ii) has Barthel Index >90/100 at the time of discharge, and (iii) has no subsequent re-admission for COVID-19 signs and symptoms • Clinical status, as assessed by the 11-category WHO Clinical Progression Scale, at Day 8 (±1) Other secondary objectives of this study are: • Safety and tolerability, based on treatment-emergent adverse events (TEAEs), Grade =3 TEAEs, serious adverse events (SAEs), serious adverse reactions (SARs), and adverse events (AEs) of special interest • Compare the efficacy and safety/tolerability between plitidepsin arms (1.5 versus 2.5 mg) in case both arms are significantly better than the control arm on the primary endpoint • Compare the percentage of patients who achieve complete recovery by Day 8 (±1), as defined above, for the pooled plitidepsin arms versus control • Percentage of patients in each study arm requiring re-admission for COVID-19 signs and symptoms • Clinical status in each study arm, as assessed by the 11-category WHO Clinical Progression Scale, at Days 4, 15, and 31 • Duration of oxygen therapy (in days) for each study arm • Percentage of patients in each study arm requiring high-flow oxygen at Days 4, 8, 15, and 31 • Percentage of patients in each study arm requiring noninvasive mechanical ventilation at Days 4, 8, 15, and 31 • Percentage of patients in each study arm requiring invasive mechanical ventilation or ECMO at Days 4, 8, 15, and 31 • Percentage of patients in each study arm requiring intensive care unit (ICU) admission at Days 4, 8, 15, and 31 • Duration of hospitalisation in ICU for each study arm • Percentage of patients receiving subsequent antiviral therapies or immun | — |
Countries
Argentina, Brazil, Bulgaria, France, Greece, Italy, Mexico, Peru, Portugal, Romania, Spain, Sweden, United Kingdom
Contacts
Public ContactAna Ruiz Madera
Pharma Mar S.A.
Outcome results
None listed