This study is for research purposes only to test plitidepsin for patients requiring hospitalization due to COVID-19.
- Conditions
- moderate COVID-19 infectionMedDRA version: 23.0Level: LLTClassification code 10084272Term: SARS-CoV-2 infectionSystem Organ Class: 100000004862Therapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2020-005951-19-PT
- Lead Sponsor
- Pharma Mar, S.A.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 205
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), antigen test by local laboratory, or any other validated method approved by the local health authority, from appropriate biological samples 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 (Appendix 13): requires hospitalization and oxygen by mask or nasal prongs/cannula
4.A maximum of 14 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 =500/mm3 (0.5 x 10^9/L)
•Platelet count =75,000/mm3 (75 x 10^9/L)
•Alanine transaminase (ALT), aspartate transaminase (AST) =3 x upper limit of normal (ULN)
•Serum bilirubin =1 x ULN (or direct bilirubin <1 x ULN when total bilirubin is above ULN).
•Calculated creatinine clearance =30 mL/min (Cockcroft-Gault equation)
•Creatine phosphokinase (CPK) =2.5 x ULN except if the patient has had recent (i.e., in the last week) shivering episodes or trauma. In that case, the level of 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 during 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.
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
1.Subjects with a pre-baseline impairment in general health condition for whatever reason except COVID-19, with a severe dependancy for daily living activities (Barthel index <60/100) 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 randomisation, based on resource utilisation requiring at least one of the following: endotracheal intubation and mechanical ventilation, O2 delivered by high-flow nasal cannula, non-invasive positive pressure ventilation, ECMO, or clinical diagnosis of respiratory failure
4.Patients with severe COVID 19, meeting score >5 on the 11-point WHO Clinical Progression Scale or presenting after an initial stabilisation prior to randomisation, any of clinical signs indicative of severe systemic illness: respiratory rate =30/min, heart rate =125/min, or PaO2/FiO2 <300. In case a direct measure of PaO2 has not been obtained, it should be imputed according to a referenced formula. For sites located over 1000m above sea level, PaO2/FiO2 ratio will be adjusted
5.Patients receiving, at randomisation, treatment with antiviral therapy against SARS-CoV-2 or requiring anti-inflammatory/immunomodulating drugs beyond glucocorticoids with the exceptions listed below
Prior administration of dexamethasone or equivalent glucocorticoid might be acceptable if:
oThe total daily dose is not higher than 10mg of dexamethasone phosphate (equivalent to dexamethasone base 8.25 mg/day) or equivalent glucocorticoids
oThe duration of the treatment does not exceed 72h prior to study treatment Day 1
Prior administration of an antiviral might be acceptable in the following circumstances:
oFor small molecules (e.g., remdesivir, molnupiravir,
nirmaltrevir/ritonavir), they must have been given for an earlier stage of the disease, outside a clinical trial, and there should be a documentation of objective clinical deterioration plus evidence of persisting positivity for SARS-CoV-2 in appropriate biological samples. Last dose of previous antiviral drugs should have been administered at least 24 h before randomisation.
oFor antiviral monoclonal antibodies, they must have been given for an earlier stage of the disease (including pre-exposure prophylaxis), outside a clinical trial, and there should be a documentation of objective clinical deterioration plus evidence of persisting positivity for SARS-CoV-2 in appropriate biological samples. Last dose of antiviral monoclonal antibodies should have been administered at least 1 week before randomisation.
6.Patients receiving treatment with chloroquine or derivatives within 8 weeks before enrolment or during the study
7.Patients receiving treatment with strong cytochrome P450 3A4 inhibitors or inducers
8.Viral illness (other than COVID-19) requiring therapy, except for patients with treated and adequately controlled (undetectable) HIV infection
9.Patients with uncontrolled known primary or secondary immunodeficiency, including chronic treatment with glucocorticoids
10.Any of the following cardiac conditions or risk
Any of the following cardiac conditions or risk factors:
-Sinus bradycardia (<50beats/min), sinus nodal dysfunction, atrioventricular block of any degree (PR >200 msec), or any other bradyarrhythmia (<50beats/min), except for patients with permanent pacemakers;
-Cardiac infarction, cardiac surgery or cardiac insufficiency episode within
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method