Extension Study in a Cohort of Adult Patients With COVID-19 Infection (E-APLICOV-PC)

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

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.

Study Overview

• Status: Completed
• Conditions: COVID-19 Infection
• Intervention / Treatment: Drug: Plitidepsin 1.5 mg / day; Drug: Plitidepsin 2.0 mg / day; Drug: Plitidepsin 2.5 mg / day

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Ciudad Real, Spain, 13005
    • Hospital General de Ciudad Real
  • Getafe, Spain, 280989
    • Hospital Universitario de Getafe
  • Guadalajara, Spain, 19002
    • Hospital Universitario de Guadalajara
  • Madrid, Spain, 28040
    • Hospital Universitario Clínico San Carlos
  • Madrid, Spain, 28009
    • Hospital General Universitario Gregorio Marañon
  • Madrid, Spain, 280029
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 280127
    • Hospital Universitario La Princesa
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol
  • Madrid
    • Boadilla del monte, Madrid, Spain, 28660
      • Hospital Universitario HM Monteprincipe
    • Pozuelo De Alarcón, Madrid, Spain, 28223
      • Hospital Universitario Quironsalud Madrid

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Experimental 1; 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; Plitidepsin 1.5 mg/day infused through a pump device over 1 hour and 30 minutes, 3 consecutive days (total dose 4.5 mg).
Experimental: Arm B: Experimental 2; 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; Plitidepsin 2.0 mg/day infused through a pump device over 1 hour and 30 minutes, 3 consecutive days (total dose 6.0 mg).
Experimental: Arm C: Experimental 3; 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; Plitidepsin 2.5 mg/day infused through a pump device over 1 hour and 30 minutes, 3 consecutive days (total dose 7.5 mg).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number and Percentage of Participants With Complications Related to Post COVID-19 Infection	Number and percentage of patients who developed 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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FEV1/FVC	FEV1/FVC mean, standard deviation.	At study inclusion, an average of 12 months after end of APLICOV-PC study.
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.
Patients With Complications Post COVID-19 Infection (Regardless Relationship, i.e. Related to COVID-19 Infection or Not).	Percentage of 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..
Ratio of Partial Pressure Arterial Oxygen (PaO2) and Fraction of Inspired Oxygen (FiO2)	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.	At study inclusion, an average of 12 months after end of APLICOV-PC study.
Forced Expiratory Volume 1 (FEV1)	FEV1 (Forced expiratory volume 1) mean, standard deviation.	At study inclusion, an average of 12 months after end of APLICOV-PC study.
Lung Diffusion Testing	Lung difussion testing: mean and standard deviation. Unit of measure: % reference theoretical value	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 Electrocardiogram Alterations	Percentage of patients with electrocardiogram alterations	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 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.	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 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; shortness of breath when hurrying on the level or walking up a slight hill;; 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;; stops for breath after walking ∼100 m or after few minutes on the level; and; too breathless to leave the house, or breathless when dressing or undressing.	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.
Arterial Oxygen Saturation (SaO2)	SaO2 (Arterial oxygen saturation) mean, standard deviation. Unit of measure: percentage of oxygen saturation	At study inclusion, an average of 12 months after end of APLICOV-PC study.
Barthel Index	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	At study inclusion, an average of 12 months after end of APLICOV-PC study.
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.
6 Minute Walking Test (Total Distance)	minute walking test mean, standard deviation. Total distance measured in meters (m)	At study inclusion, an average of 12 months after end of APLICOV-PC study.
6 Minute Walking Test (Expected Distance)	minute walking test mean, standard deviation. Expected distance (the predicted distance that a patient could walk) measured in meters (m)	At study inclusion, an average of 12 months after end of APLICOV-PC study.
6 Minute Walking Test (Percentage of Predicted Distance)	6 minute walking test mean, standard deviation. Unit of measure: Percentage of predicted distance	At study inclusion, an average of 12 months after end of APLICOV-PC study.
6 Minute Walking Test (Number of Laps of 60 m)	6 minute walking test mean, standard deviation. Unit of measure: Number of laps of 60 m	At study inclusion, an average of 12 months after end of APLICOV-PC study.

Collaborators and Investigators

• Sponsor: PharmaMar
• Collaborators: Apices Soluciones S.L.
• Investigators: Principal Investigator: Pedro Landete, MD, Hospital Universitario La Princesa; Principal Investigator: Pablo Guisado-Vasco, MD, Quironsalud; Principal Investigator: Roger Paredes, MD, Germans Trias i Pujol Hospital; Principal Investigator: José Felipe Varona, MD, Hospital Universitario HM Monteprincipe

Publications and helpful links

General Publications

• Varona JF, Landete P, Paredes R, Vates R, Torralba M, Guisado-Vasco P, Porras L, Munoz P, Gijon P, Ancochea J, Saiz E, Meira F, Jimeno JM, Lopez-Martin JA, Estrada V. Plitidepsin in adult patients with COVID-19 requiring hospital admission: A long-term follow-up analysis. Front Cell Infect Microbiol. 2023 Feb 22;13:1097809. doi: 10.3389/fcimb.2023.1097809. eCollection 2023.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): January 25, 2022
• Primary Completion (Actual): March 16, 2022
• Study Completion (Actual): March 16, 2022

Study Registration Dates

• First Submitted: November 8, 2021
• First Submitted That Met QC Criteria: November 15, 2021
• First Posted (Actual): November 16, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 11, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: COVID-19; Plitidepsin; Post-COVID morbidity
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Respiratory Tract Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Infections; Communicable Diseases
• Other Study ID Numbers: AV-APL-A-003-21; 2021-004966-37 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No