Plitidepsin Versus Control in Immunocompromised Adult Participants With Symptomatic COVID-19 Requiring Hospital Care (NEREIDA)

NCT ID: NCT05705167

Last Updated: 2024-12-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 37 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-19
• Study Completion Date: 2024-04-19

Brief Summary

The primary objective of this study is to evaluate efficacy of plitidepsin in pre-specified groups of immunocompromised patients with symptomatic COVID-19 requiring hospital care versus control in terms of mortality.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Plitidepsin 2.5 mg

Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 60-minute intravenous (IV) infusion, every 24 hours for 3 consecutive days, at a dose of 2.5 mg) will be administered to participants of the following groups:

• Group 1 - Participants receiving immune-suppression due to haematopoietic or organ transplantation.
• Group 2 - Participants receiving B-cell depleting therapies.
• Group 3 - Participants receiving other immune-suppressive therapies.
• Group 4 - Other situations with immune deficiencies.

Group Type: EXPERIMENTAL

Plitidepsin

Intervention Type: DRUG

IV infusion over 60-minutes

Control

Best standard care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) ± other regulatory-approved antiviral (if clinically indicated) will be administered to participants of the following groups:

• Group 1 - Participants receiving immune-suppression due to haematopoietic or organ transplantation.
• Group 2 - Participants receiving B-cell depleting therapies.
• Group 3 - Participants receiving other immune-suppressive therapies.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Plitidepsin

IV infusion over 60-minutes

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Signed informed consent obtained prior to initiation of any study-specific procedures and study treatment.
• Participant aged ≥18 years.
• Participant diagnosed COVID-19, with the following characteristics:

1. A regulatory-approved test, collected no more than 3 days prior to study randomisation, with either a Ct value ≤30 or a positive antigen test.

2. Presence of any of the selected signs/symptom listed in the COVID-19 signs/symptoms checklist within the last 24 hours.

• Participant already admitted or requiring hospital care for symptomatic COVID-19, for which at least one antiviral has failed or cannot be used (i.e., contraindication, absence of labelled indication, guidelines or drug unavailability), after a minimum washout period of 24 hours for small molecules (e.g., remdesivir, molnupiravir, nirmaltrevir, ritonavir) and 5 days for antiviral monoclonal antibodies (e.g., tixagevimab + cilgavimab) or convalescent plasma.
• Adequate bone marrow, liver, kidney, and metabolic function, defined by the following tests performed at local laboratory:

1. Absolute neutrophil count ≥500/mm^3 (0.5 x 109/L).

2. Platelet count ≥ 50 000/mm3 (50 x 109/L).

3. Alanine transaminase (ALT) ≤3 x upper limit of normal (ULN) (≤5 x ULN if preexistent liver involvement by the underlying disease).

4. Serum bilirubin ≤1.5 x ULN (or direct bilirubin <1.5 x ULN when total bilirubin is above ULN).

5. Estimated glomerular filtration rate ≥30 mL/min (CKD-EPI Creatinine Equation [2021]).

• Females of child-bearing potential must have a negative serum or urine pregnancy test by local laboratory at screening and must be non-lactating.
• Females of child-bearing potential and fertile males with partners of child-bearing potential must use contraceptive methods as specified in the protocol.

• Group 1 - Patients receiving, within the last 30 days, immune-suppressive therapy due to haematopoietic or organ transplantation.
• Group 2 - Participants receiving B-cell depleting therapies within the last 6 months (with the exception of CAR-T cell therapy for which time restriction is not applicable).
• Group 3 - Participants receiving, within the last 30 days, other immune-suppressive therapies.
• Group 4 - Other situations with immunodeficiency.

1. Primary immune deficiencies.

2. Human immunodeficiency virus (HIV) infection, with CD4^+ T lymphocyte < 200 cells/μL in the last month.

3. Radiation therapy within the last 3 months- requires documentation of ALC < 500 cells/μL.

4. Haematological neoplasia or myelodysplasia not currently receiving any therapy.

5. Other situations with a documentation of ALC < 500 cells/μL.

Exclusion Criteria

• Evidence of critical illness.
• Any of the following cardiac conditions or risk factors:

1. Cardiac infarction or cardiac surgery episode within the last month.

2. History of known congenital QT prolongation.

3. Known structural cardiomyopathy with abnormal left ventricular ejection fraction (LVEF) (<50%).

4. Current clinical evidence of heart failure or acute cardiac ischaemia (New York Heart Association (NYHA) class III-IV).

• Hypersensitivity to the active ingredient or any of the excipients (mannitol, macrogolglycerol hydroxystearate, and ethanol) or contraindication to receive dexamethasone, antihistamine H1/H2, or anti-serotoninergic 5HT3 agents.
• Females who are pregnant or breast-feeding.
• Females and males with partners of child-bearing potential who are not using at least 1 protocol-specified method of contraception.
• Any situation currently requiring increasing needs of immune-suppressive agents.
• Any other clinically significant medical condition or laboratory abnormality that, in the opinion of the investigator, would jeopardise the safety of the participant or potentially impact on participant compliance or the safety/efficacy observations in the study.
• Participation in another clinical study involving an investigational drug within 30 days prior to screening.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PharmaMar

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

Leuven, Flemish Brabant, Belgium

Cancer Research Centre of Lyon

Lyon, Auvergne-Rhône-Alpes, France

Hôpitaux Civils de Colmar - Centre Hospitalier Louis Pasteur

Colmar, Grand Est, France

Centre Hospitalier Régional Universitaire de Tours

Tours, Indre-et-Loire, France

Centre Hospitalier de la Côte Basque

Bayonne, Pyrénées-Atlantiques, France

Les Hôpitaux Universitaires de Strasbourg

Strasbourg, , France

The First University Clinic of the Tbilisi State Medical University

Tbilisi, , Georgia

Ltd Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic

Tbilisi, , Georgia

Academician Vakhtang Bochorishvili Clinic

Tbilisi, , Georgia

General Hospital of Athens Evangelismos

Athens, Attica, Greece

Laiko General Hospital of Athens

Athens, Attica, Greece

Alexandra General Hospital

Athens, Attica, Greece

University General Hospital Attikon

Athens, Attica, Greece

University Hospital of Ioannina

Ioannina, Epirus, Greece

General Hospital for Thoracic Diseases Sotiria

Athens, , Greece

Országos Korányi Pulmonológiai Intézet

Budapest, , Hungary

Sheba Medical Center Hospital - Tel Hashomer

Ramat Gan, Tel Aviv, Israel

IRCCS Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani

Roma, Rome, Italy

Ente Ospedaliero Ospedali Galliera

Genova, , Italy

Wojewódzki Specjalistyczny Szpital im. Dr. Władysława Biegańskiego

Lodz, Lódzkie, Poland

Hospital da Senhora da Oliveira - Guimarães

Guimarães, Braga District, Portugal

Centro Hospitalar Universitário Lisboa Norte, E.P.E - Hospital De Santa Maria

Lisbon, Lisbon District, Portugal

Hospital Pedro Hispano

Senhora da Hora, , Portugal

Centro Hospitalar de Vila Nova de Gaia/Espinho

Vila Nova de Gaia, , Portugal

Hospital Germans Trias i Pujol

Badalona, Barcelona, Spain

Hospital Universitario Quirónsalud Madrid

Pozuelo de Alarcón, Madrid, Spain

Hospital Alvaro Cunqueiro - Clinico Universitario Vigo

Vigo, Pontevedra, Spain

Hospital del Mar - Parc de Salut Mar

Barcelona, , Spain

Vall d'Hebron Institut de Recerca

Barcelona, , Spain

Hospital Clinic de Barcelona

Barcelona, , Spain

Hospital San Pedro de Alcantara

Cáceres, , Spain

Hospital Universitario de La Princesa

Madrid, , Spain

Hospital General Universitario Gregorio Marañón

Madrid, , Spain

MD Anderson Cancer Center Madrid

Madrid, , Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Hospital Clínico San Carlos

Madrid, , Spain

Hospital Universitario Fundación Jiménez Díaz

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario HM Sanchinarro

Madrid, , Spain

Hospital Regional Universitario de Málaga - Hospital General

Málaga, , Spain

Complejo Asistencial Universitario de Salamanca - Hospital Clínico

Salamanca, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, England, United Kingdom

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Countries

Belgium; France; Georgia; Greece; Hungary; Israel; Italy; Poland; Portugal; Spain; United Kingdom

References

Landete P, Caliman-Sturdza OA, Lopez-Martin JA, Preotescu L, Luca MC, Kotanidou A, Villares P, Iglesias SP, Guisado-Vasco P, Saiz-Lou EM, Del Carmen Farinas-Alvarez M, de Lucas EM, Perez-Alba E, Cisneros JM, Estrada V, Hidalgo-Tenorio C, Poulakou G, Torralba M, Fortun J, Garcia-Ocana P, Lemaignen A, Marcos-Martin M, Molina M, Paredes R, Perez-Rodriguez MT, Raev D, Ryan P, Meira F, Gomez J, Torres N, Lopez-Mendoza D, Jimeno J, Varona JF. A Phase III Randomized Controlled Trial of Plitidepsin, a Marine-Derived Compound, in Hospitalized Adults With Moderate COVID-19. Clin Infect Dis. 2024 Oct 15;79(4):910-919. doi: 10.1093/cid/ciae227.

Reference Type: DERIVED

PMID: 39182994 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2022-002489-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AV-APL-B-002-22

Identifier Type: -

Identifier Source: org_study_id