In December 2019, Wuhan, in Hubei province, China, became the center of an outbreak of pneumonia of unknown cause. In a short time, Chinese scientists had shared the genome information of a novel coronavirus (SARS-CoV-2) from these pneumonia patients and developed a real-time reverse transcription PCR (real-time RT-PCR) diagnostic assay. Given no specific antiviral therapy for COVID-19 and the ready availability of plitidepsin as a potential antiviral agent, based on pre-clinical studies, this randomized, parallel and proof of concept trial will evaluate the safety of three doses of plitidepsin in patients hospitalized with COVID-19.
In December 2019, a new infectious respiratory disease emerged in Wuhan, China. The agent that caused this pneumonia was identified as a new virus in the Coronaviridae family (SARS-CoV-2) and the clinical symptomatology associated with the virus has been named COVID-19. COVID-19 is currently a public health emergency. Plitidepsin is an authorized drug in Australia for the treatment of multiple myeloma. Antiviral activity of plitidepsin has been analyzed in a human hepatoma cell line infected with the HCoV-229E-GFP virus, a virus similar to the SARS-CoV-2 virus. Taking into account that the available safety data from plitidepsin comes from patients with solid tumors that received treatment with a regimen of administration of plitidepsin for 5 consecutive days, we propose a multicenter, randomized, proof-of-concept clinical trial to assess the safety profile of 3 different dose levels of plitidepsin administered three consecutive days, in adult patients with confirmed diagnosis of COVID-19 who require hospital admission. This study aims to assess safety and toxicity profile and also preliminary efficacy of plitidepsin at each dose level administered according to the proposed administration scheme in patients with COVID-19 who require hospital admission. Main objective is to select the recommended dose levels of plitidepsin for a future phase II / III efficacy study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
46
Plitidepsin 1.5 mg/day will be IV infused through a pump device over 1 hour and 30 minutes, 3 consecutive days. All patients must receive the following prophylactic medications 20-30 minutes before the infusion of plitidepsin: * Diphenhydramine hydrochloride 25 mg iv or equivalent. * Ranitidine 50 mg iv or equivalent. * Dexamethasone 8 mg iv. * Ondansetron 8 mg i.v. 15 minutes infusion or equivalent. * Ondansetron 4 mg p.o. administered every 12 hours until 48 hours after the last administration of plitidepsin.
Plitidepsin 2.0 mg/day will be IV infused through a pump device over 1 hour and 30 minutes, 3 consecutive days. All patients must receive the following prophylactic medications 20-30 minutes before the infusion of plitidepsin: * Diphenhydramine hydrochloride 25 mg iv or equivalent. * Ranitidine 50 mg iv or equivalent. * Dexamethasone 8 mg iv. * Ondansetron 8 mg i.v. 15 minutes infusion or equivalent. * Ondansetron 4 mg p.o. administered every 12 hours until 48 hours after the last administration of plitidepsin.
Plitidepsin 2.5 mg/day will be IV infused through a pump device over 1 hour and 30 minutes, 3 consecutive days. All patients must receive the following prophylactic medications 20-30 minutes before the infusion of plitidepsin: * Diphenhydramine hydrochloride 25 mg iv or equivalent. * Ranitidine 50 mg iv or equivalent. * Dexamethasone 8 mg iv. * Ondansetron 8 mg i.v. 15 minutes infusion or equivalent. * Ondansetron 4 mg p.o. administered every 12 hours until 48 hours after the last administration of plitidepsin.
Hospital Universitario Hm Montepríncipe
Boadilla del Monte, Madrid, Spain
Hospital Germans Trias i Pujol
Badalona, Spain
Hospital Clínic de Barcelona
Barcelona, Spain
Hospital de la Santa Creu i Sant Pau
Barcelona, Spain
Hospital Ciudad Real
Ciudad Real, Spain
Hospital Universitario de Getafe
Getafe, Spain
Hospital Universitario de Guadalajara
Guadalajara, Spain
Hospital Universitari Arnau de Vilanova
Lleida, Spain
Hospital La Princesa
Madrid, Spain
Hospital Gregorio Marañón
Madrid, Spain
...and 3 more locations
Frequency of Occurrence of Neutropenia ≥ Grade 3
Percentage of patients with Neutropenia ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time frame: At days 3, 7, 15 and 31
Frequency of Occurrence of Thrombocytopenia ≥ Grade 3
Percentage of patients with Thrombocytopenia ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time frame: At days 3, 7, 15 and 31
Frequency of Occurrence of Anemia ≥ Grade 3
Percentage of patients with Anemia ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time frame: At days 3, 7, 15 and 31
Frequency of Occurrence of Lymphopenia ≥ Grade 3
Percentage of patients with Lymphopenia ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time frame: At days 3, 7, 15 and 31
Frequency of Occurrence of CPK Increase ≥ Grade 3
Percentage of patients with CPK increase ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time frame: At days 3, 7, 15 and 31
Frequency of Occurrence of Increase ALT and / or AST ≥ Grade 3
Percentage of patients with Increase ALT and / or AST ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time frame: At days 3, 7, 15 and 31
Frequency of Occurrence of Increase Total Bilirubin or Direct Bilirubin ≥ Grade 3
Percentage of patients with Increase total bilirubin or direct bilirubin ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time frame: At days 3, 7, 15 and 31
Frequency of Occurrence of Neurotoxicity ≥ Grade 3
Percentage of patients with Neurotoxicity ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time frame: At days 3, 7, 15 and 31
Frequency of Occurrence of QT-QTc Interval Extension ≥ Grade 3
Percentage of patients with QT-QTc interval extension ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time frame: At days 3, 7, 15 and 31
Frequency of Occurrence of Other Adverse Events ≥ Grade 3
Percentage of patients with Other adverse events ≥ grade 3 according to NCI-CTCAE v5.0 criteria.
Time frame: At days 3, 7, 15 and 31.
Percentage of Patients in Whom Treatment Cannot be Completed.
Percentage of patients in whom treatment cannot be completed and the reasons.
Time frame: At 3 days from the first dose of study treatment
Percentage of Patients With Adverse Events.
Percentage of patients with adverse events.
Time frame: At days 3, 7, 15 and 31
Percentage of Patients With Serious Adverse Events.
Percentage of patients with serious adverse events.
Time frame: At days 3, 7, 15 and 31
Percentage of Patients With ECG Abnormalities.
Percentage of patients with ECG abnormalities.
Time frame: At days 2, 3, 4, 5, 6, 7, 15 and 31
Change in the Viral Load of SARS-CoV-2
Median change in the viral load of SARS-CoV-2 from baseline.
Time frame: At days 4, 7, 15 and 31
Time to Negative PCR Test for COVID-19
Time from inclusion/randomization to date of negative PCR test for COVID-19
Time frame: Up to 31 days + 3 days for window period
Mortality
Percentage of patients who die during the study
Time frame: At days 7, 15 and 31
Percentage of Patients Requiring Invasive Mechanical Ventilation and / or ICU Admission
Percentage of patients requiring invasive mechanical ventilation and / or ICU admission
Time frame: At days 7, 15 and 31
Percentage of Patients Requiring Non-invasive Mechanical Ventilation
Percentage of patients requiring non-invasive mechanical ventilation
Time frame: At days 7, 15 and 31
Percentage of Patients Requiring Oxygen Therapy
Percentage of patients requiring oxygen therapy
Time frame: At days 7, 15 and 31
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