This study is for research purposes only to test plitidepsin for patients requiring hospitalization due to COVID-19.

Phase 1

• Conditions: moderate COVID-19 infection; MedDRA version: 23.0Level: LLTClassification code 10084272Term: SARS-CoV-2 infectionSystem Organ Class: 100000004862; Therapeutic area: Diseases [C] - Virus Diseases [C02]

• Registration Number: EUCTR2020-005951-19-BG
• Lead Sponsor: Pharma Mar, S.A.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-05-10
• Last Update Posted: 23 May 2022

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 609

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), 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 nonlactating
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

Exclusion Criteria

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:
o The total daily dose is not higher than 10mg of dexamethasone
phosphate (equivalent to dexamethasone base 8.25 mg/day) or
equivalent glucocorticoids
o The 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:
o For 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.
o For 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
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Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified