Extension Study in a Cohort of Adult Patients With COVID-19 Infection

Study Overview
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Brief Summary
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The main objective of this study is to evaluate the incidence of post-COVID morbidity and characterize the complications profile in patients who participated in the APLICOV-PC study. APLICOV-PC study was a multicenter, randomized, proof-of-concept clinical trial to assess the safety profile of 3 different dose levels of plitidepsin (1,5 mg, 2,0 mg and 2,5 mg) administered three consecutive days, in adult patients with confirmed diagnosis of COVID-19 who require hospital admission.

Detailed Description
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The APLICOV-PC proof of concept study demonstrated the antiviral activity of plitidepsin in terms of reducing viral load, inducing recovery, and impact on lymphocyte reconstitution and other inflammatory parameters. A percentage of patients, which varies between 10 and 25%, continue to show symptoms at 3 months after contracting the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: For some of them this significantly restricts their life, requiring them to take long-term sickness leave from work, and leaving them with sequelae that may continue for more than one year. With this study, Pharmamar intends to evaluate whether the treatment with plitidepsin, by attaining a reduction in the viral load and a faster recovery of the patient, could have a relevant impact on the emergence of sequelae resulting from the SARS-CoV-2 infection.

Official Title
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Extension Study in a Cohort of Adult Patients With SARS-CoV-2 Infection Requiring Hospital Admission and Received Treatment With Plitidepsin in the APLICOV-PC Study

Conditions
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COVID-19 Infection

Intervention / Treatment
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* Drug: Plitidepsin 1.5 mg / day
* Drug: Plitidepsin 2.0 mg / day
* Drug: Plitidepsin 2.5 mg / day


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient who participated in the APLICOV-PC study receiving treatment with plitidepsin and who gives consent. Exclusion Criteria: There are no exclusion criteria for this study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Interventional Model Description: Follow up Multicentric extension study of APLICOV-PC clinical trial.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Experimental 1<br>In the APLICOV-PC study, patients of arm A received 1.5 mg of plitidepsin / day for 3 consecutive days (total dose 4.5 mg). | Drug: Plitidepsin 1.5 mg / day<br>* Plitidepsin 1.5 mg/day infused through a pump device over 1 hour and 30 minutes, 3 consecutive days (total dose 4.5 mg).<br>|
| Experimental: Arm B: Experimental 2<br>In the APLICOV-PC study, patients of arm B received 2.0 mg of plitidepsin / day for 3 consecutive days (total dose 6.0 mg). | Drug: Plitidepsin 2.0 mg / day<br>* Plitidepsin 2.0 mg/day infused through a pump device over 1 hour and 30 minutes, 3 consecutive days (total dose 6.0 mg).<br>|
| Experimental: Arm C: Experimental 3<br>In the APLICOV-PC study, patients of arm C received 2.5 mg of plitidepsin / day for 3 consecutive days (total dose 7.5 mg). | Drug: Plitidepsin 2.5 mg / day<br>* Plitidepsin 2.5 mg/day infused through a pump device over 1 hour and 30 minutes, 3 consecutive days (total dose 7.5 mg).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of complications | Percentage of patients who developed complications related to COVID-19 infection | Since last visit of APLICOV-PC study until the end of this extension study, an average of 12 months. | 
| Patients requiring hospital readmission | Percentage of patients requiring hospital readmission | Since last visit of APLICOV-PC study until the end of this extension study, an average of 12 months. | 
| Patients requiring oxygen therapy | Percentage of patients requiring oxygen therapy | Since last visit of APLICOV-PC study until the end of this extension study, an average of 12 months. | 
| Duration of oxygen therapy | Duration of oxygen therapy mean, standard deviation. | From start of oxygen therapy until end of oxygen therapy, assessed up to 12 months | 
| Patients with complications | Percentage of patients with complications | Since last visit of APLICOV-PC study until the end of this extension study, an average of 12 months.. | 
| Barthel index | Percentage of patients at each category according to the score obtained: 0-20: Total dependence; 21-60: Severe dependence; 61-90: Moderate dependence; 91-99: Low dependence; 100: Independence | At study inclusion, an average of 12 months after end of APLICOV-PC study. | 
| Arterial oxygen saturation (SaO2) | SaO2 mean, standard deviation. | At study inclusion, an average of 12 months after end of APLICOV-PC study. | 
| Ratio of partial pressure arterial oxygen (PaO2) and fraction of inspired oxygen (FiO2) | PaO2/FiO2 mean, standard deviation. | At study inclusion, an average of 12 months after end of APLICOV-PC study. | 
| Forced vital capacity (FVC) | FVC mean, standard deviation. | At study inclusion, an average of 12 months after end of APLICOV-PC study. | 
| Forced expiratory volume 1 (FEV1) | FEV1 mean, standard deviation. | At study inclusion, an average of 12 months after end of APLICOV-PC study. | 
| FEV1/FVC | FEV1/FVC mean, standard deviation. | At study inclusion, an average of 12 months after end of APLICOV-PC study. | 
| Diffusion test | Diffusion test mean, standard deviation. | At study inclusion, an average of 12 months after end of APLICOV-PC study. | 
| 6 minute walking test | 6 minute walking test mean, standard deviation. | At study inclusion, an average of 12 months after end of APLICOV-PC study. | 
| Modified Medical Research Council (mMRC) Dyspnea Scale | Percentage of patients in each category of the mMRC dyspnea scale | At study inclusion, an average of 12 months after end of APLICOV-PC study. | 
| Patients with alterations in chest radiography | Percentage of patients with alterations in chest radiography | At study inclusion, an average of 12 months after end of APLICOV-PC study. | 
| Patients with ≥grade 2 alterations in laboratory parameters | Percentage of patients with ≥grade 2 alterations in laboratory parameters | At study inclusion.At study inclusion, an average of 12 months after end of APLICOV-PC study. | 
| Patients with electrocardiogram alterations | Percentage of patients with electrocardiogram alterations | At study inclusion, an average of 12 months after end of APLICOV-PC study. | 
| Patients with echocardiogram / multigated acquisition scan (ECHO/MUGA) alterations | Percentage of patients with cardiac ECHO/MUGA alterations in patients who suffered a relevant cardiac event during their participation in the APLICOV-PC study, | At study inclusion, an average of 12 months after end of APLICOV-PC study. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Plitidepsin, COVID-19, Post-COVID morbidity