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

Phase 1

Completed

Conditions: COVID-19 Infection

Interventions: Drug: Plitidepsin 1.5 mg / day
Drug: Plitidepsin 2.5 mg / day
Drug: Plitidepsin 2.0 mg / day

Registration Number: NCT05121740

Lead Sponsor: PharmaMar

Brief Summary: 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: 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 34

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Arm A: Experimental 1	Plitidepsin 1.5 mg / day	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).
Arm C: Experimental 3	Plitidepsin 2.5 mg / day	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).
Arm B: Experimental 2	Plitidepsin 2.0 mg / day	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).

Primary Outcome Measures

Name	Time	Method
Number and Percentage of Participants With Complications Related to Post COVID-19 Infection	Since last visit of APLICOV-PC study until the end of this extension study, an average of 12 months.	Number and percentage of patients who developed complications related to post COVID-19 infection

Secondary Outcome Measures

Name	Time	Method
Patients Requiring Oxygen Therapy	Since last visit of APLICOV-PC study until the end of this extension study, an average of 12 months.	Percentage of patients requiring oxygen therapy
Patients With Complications Post COVID-19 Infection (Regardless Relationship, i.e. Related to COVID-19 Infection or Not).	Since last visit of APLICOV-PC study until the end of this extension study, an average of 12 months..	Percentage of patients with complications Post COVID-19 Infection (Regardless Relationship, i.e. Related to COVID-19 Infection or Not).
Ratio of Partial Pressure Arterial Oxygen (PaO2) and Fraction of Inspired Oxygen (FiO2)	At study inclusion, an average of 12 months after end of APLICOV-PC study.	PaO2/FiO2 (Ratio of partial pressure arterial oxygen and fraction of inspired oxygen) mean, standard deviation. PaO2/FiO2 ratio to evaluate disease severity and discriminate between 'Moderate' and 'Severe' categories according to FDA guidance.
Lung Diffusion Testing	At study inclusion, an average of 12 months after end of APLICOV-PC study.	Lung difussion testing: mean and standard deviation. Unit of measure: % reference theoretical value
Forced Expiratory Volume 1 (FEV1)	At study inclusion, an average of 12 months after end of APLICOV-PC study.	FEV1 (Forced expiratory volume 1) mean, standard deviation.
Patients With Alterations in Chest Radiography	At study inclusion, an average of 12 months after end of APLICOV-PC study.	Percentage of patients with alterations in chest radiography
Patients With Electrocardiogram Alterations	At study inclusion, an average of 12 months after end of APLICOV-PC study.	Percentage of patients with electrocardiogram alterations
Patients With ≥Grade 2 Alterations in Laboratory Parameters	At study inclusion, an average of 12 months after end of APLICOV-PC study.	Percentage of patients with ≥grade 2 alterations in laboratory parameters Grade measured according to NCI-CTCAE v5.0 (National Cancer Institute - Common Terminology Criteria for Adverse Events version 5.0) where Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL\* Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.
Modified Medical Research Council (mMRC) Dyspnea Scale	At study inclusion, an average of 12 months after end of APLICOV-PC study.	Percentage of patients in each category of the Modified Medical Research Council (mMRC) dyspnea scale. The mMRC scale is a self-rating tool to measure the degree of disability that breathlessness poses on day-to-day activities on a scale from 0 to 4: 0, no breathlessness except on strenuous exercise; 1. shortness of breath when hurrying on the level or walking up a slight hill; 2. walks slower than people of same age on the level because of breathlessness or has to stop to catch breath when walking at their own pace on the level; 3. stops for breath after walking ∼100 m or after few minutes on the level; and 4. too breathless to leave the house, or breathless when dressing or undressing.
FEV1/FVC	At study inclusion, an average of 12 months after end of APLICOV-PC study.	FEV1/FVC mean, standard deviation.
Forced Vital Capacity (FVC)	At study inclusion, an average of 12 months after end of APLICOV-PC study.	FVC mean, standard deviation.
Arterial Oxygen Saturation (SaO2)	At study inclusion, an average of 12 months after end of APLICOV-PC study.	SaO2 (Arterial oxygen saturation) mean, standard deviation. Unit of measure: percentage of oxygen saturation
Barthel Index	At study inclusion, an average of 12 months after end of APLICOV-PC study.	The Barthel index measures the extent to which somebody can function independently and has mobility in their activities of daily living (ADL) i.e. feeding, bathing, grooming, dressing, bowel control, bladder control, toileting, chair transfer, ambulation and stair climbing. 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
Patients Requiring Hospital Readmission	Since last visit of APLICOV-PC study until the end of this extension study, an average of 12 months.	Percentage of patients requiring hospital readmission
6 Minute Walking Test (Total Distance)	At study inclusion, an average of 12 months after end of APLICOV-PC study.	minute walking test mean, standard deviation. Total distance measured in meters (m)
6 Minute Walking Test (Expected Distance)	At study inclusion, an average of 12 months after end of APLICOV-PC study.	minute walking test mean, standard deviation. Expected distance (the predicted distance that a patient could walk) measured in meters (m)
6 Minute Walking Test (Percentage of Predicted Distance)	At study inclusion, an average of 12 months after end of APLICOV-PC study.	6 minute walking test mean, standard deviation. Unit of measure: Percentage of predicted distance
6 Minute Walking Test (Number of Laps of 60 m)	At study inclusion, an average of 12 months after end of APLICOV-PC study.	6 minute walking test mean, standard deviation. Unit of measure: Number of laps of 60 m

Trial Locations

Locations (10): Hospital Universitario Quironsalud Madrid
🇪🇸
Pozuelo De Alarcón, Madrid, Spain
Hospital Universitari Germans Trias i Pujol
🇪🇸
Badalona, Barcelona, Spain
Hospital Universitario HM Montepríncipe
🇪🇸
Boadilla del monte, Madrid, Spain
Hospital General de Ciudad Real
🇪🇸
Ciudad Real, Spain
Hospital Universitario de Getafe
🇪🇸
Getafe, Spain
Hospital Universitario de Guadalajara
🇪🇸
Guadalajara, Spain
Hospital Universitario Ramón y Cajal
🇪🇸
Madrid, Spain
Hospital General Universitario Gregorio Marañón
🇪🇸
Madrid, Spain
Hospital Universitario La Princesa
🇪🇸
Madrid, Spain
Hospital Universitario Clínico San Carlos
🇪🇸
Madrid, Spain