COVID-19 trials registries data warehouse

https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-005951-19/RO

Pharma Mar S.A. - Ana Ruiz Madera

aruiz@pharmamar.com

2022-05-02

Recruiting

RCT

Randomized

Parallel

Open label

multi-center

Treatment

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 <30 breaths per minute, 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 PaO2/FiO2 should be >= 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 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). 4. Onset of COVID-19 symptoms no later than 6 days prior 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 ≥1000/mm3 (1.0 x 109/L) Lymphocyte count ≥500/mm3 (0.5 x 109/L) Platelet count ≥100 000/mm3 (100 x 109/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 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.

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 <300) 5. Patients receiving treatment with antivirals, IL-6 receptor inhibitor, corticosteroids, or immunomodulatory drugs for COVID-19 infection within 4 weeks before enrolment 6. 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 7. Patients receiving treatment with chloroquine or derivatives within 8 weeks before enrolment or during the study 8. Receiving treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers (see Appendix 4) 9. Viral illness (other than COVID-19) requiring therapy, except for patients with treated and adequately controlled (undetectable) human immunodeficiency virus infection are eligible 10. Any of the following cardiac conditions or risk factors: - Sinus bradycardia (<50 beats/min), sinus nodal dysfunction (sick sinus disease), atrio-ventricular block of any degree (PR >200 msec), or any other bradyarrhthymia (< 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, 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 potential at screening) or breast feeding 14. 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 protocolspecified method of contraception 15. 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.

6

Pharma Mar, S.A.

18

100

Argentina;Brazil;Bulgaria;France;Italy;Mexico;Peru;Portugal;Romania;Spain;Sweden;United Kingdom

Moderate disease at enrollment

3: Moderate disease at enrollment

39

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

Declared number of arm (3.0) differs from found arms (6.0)

Phase 3

[{"arm_notes": "1 mg", "treatment_id": 400, "treatment_name": "Dexamethasone", "treatment_type": "Corticosteroids", "pharmacological_treatment": "Pharmacological treatment"}, {"arm_notes": "", "treatment_id": 1003, "treatment_name": "Plitidepsin", "treatment_type": "Others pharmacological treatment", "pharmacological_treatment": "Pharmacological treatment"}, {"arm_notes": "4 mg", "treatment_id": 400, "treatment_name": "Dexamethasone", "treatment_type": "Corticosteroids", "pharmacological_treatment": "Pharmacological treatment"}, {"arm_notes": "5 mg/ml", "treatment_id": 1099, "treatment_name": "Remdesivir", "treatment_type": "Antivirals", "pharmacological_treatment": "Pharmacological treatment"}, {"arm_notes": "100 mg", "treatment_id": 1099, "treatment_name": "Remdesivir", "treatment_type": "Antivirals", "pharmacological_treatment": "Pharmacological treatment"}, {"arm_notes": "3.3 mg/ml", "treatment_id": 400, "treatment_name": "Dexamethasone", "treatment_type": "Corticosteroids", "pharmacological_treatment": "Pharmacological treatment"}]