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

NCT05705167 | Terminated Phase 2 Results DMC

• 2 other identifiers: AV-APL-B-002-222022-002489-34
• Study Type: interventional
• Target: 37
• Locations: 11 countries
• Sites: 44

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

Keywords

COVID-19; Plitidepsin

Outcome Measures

Primary Outcomes (1)

• One-month All-cause Mortality Rate

  In the event of the participant initiating another non-protocol therapy, 1-month all-cause mortality rate was evaluated regardless of initiation of new non-protocol therapy.

  Day 1 to Day 30 (±2)

Secondary Outcomes (7)

• Time to Confirmed Negativisation in SARS-CoV-2 Antigen Test or Real Time Polymerase Chain Reaction (RT-PCR) Cycle Threshold (Ct) > 30

  Day 1 to Day 60 (±3)

• Time to Sustained End of COVID-related Hospital Care

  Day 1 to Day 60 (±3)

• Time to Sustained Improvement and Resolution of Selected COVID-19 Signs/Symptoms

  Day 1 to Day 60 (±3)

• Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS)

  Days 4 (±1), 8 (±1), 15 (±1), 30 (±2), and 60 (±3)

• Number of Participants Requiring Oxygen Therapy

  Days 4 (±1), 8 (±1), 15 (±1), 30 (±2), and 60 (±3)

Study Arms (2)

Plitidepsin 2.5 mg

EXPERIMENTAL

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.

Drug: Plitidepsin

Control

NO INTERVENTION

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.

Interventions

Plitidepsin DRUG

IV infusion over 60-minutes

Plitidepsin 2.5 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• 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:
• Absolute neutrophil count ≥500/mm\^3 (0.5 x 109/L).
• Platelet count ≥ 50 000/mm3 (50 x 109/L).
• Alanine transaminase (ALT) ≤3 x upper limit of normal (ULN) (≤5 x ULN if preexistent liver involvement by the underlying disease).
• Serum bilirubin ≤1.5 x ULN (or direct bilirubin \<1.5 x ULN when total bilirubin is above ULN).
• 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.

You may not qualify if:

• Evidence of critical illness.
• Any of the following cardiac conditions or risk factors:
• Cardiac infarction or cardiac surgery episode within the last month.
• History of known congenital QT prolongation.
• Known structural cardiomyopathy with abnormal left ventricular ejection fraction (LVEF) (\<50%).
• 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.

Sponsors & Collaborators

• PharmaMar: lead

Study Sites (44)

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

Leuven, Flemish Brabant, 3000, Belgium

Location

Cancer Research Centre of Lyon

Lyon, Auvergne-Rhône-Alpes, 69373, France

Location

Hôpitaux Civils de Colmar - Centre Hospitalier Louis Pasteur

Colmar, Grand Est, 68024, France

Location

Centre Hospitalier Régional Universitaire de Tours

Tours, Indre-et-Loire, 37044, France

Location

Centre Hospitalier de la Côte Basque

Bayonne, Pyrénées-Atlantiques, 64109, France

Location

Les Hôpitaux Universitaires de Strasbourg

Strasbourg, 67091, France

Location

The First University Clinic of the Tbilisi State Medical University

Tbilisi, 0141, Georgia

Location

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

Tbilisi, 0144, Georgia

Location

Academician Vakhtang Bochorishvili Clinic

Tbilisi, 4600, Georgia

Location

General Hospital of Athens Evangelismos

Athens, Attica, 10676, Greece

Location

Laiko General Hospital of Athens

Athens, Attica, 11527, Greece

Location

Alexandra General Hospital

Athens, Attica, 11528, Greece

Location

University General Hospital Attikon

Athens, Attica, 124 62, Greece

Location

University Hospital of Ioannina

Ioannina, Epirus, 45500, Greece

Location

General Hospital for Thoracic Diseases Sotiria

Athens, 11527, Greece

Location

Országos Korányi Pulmonológiai Intézet

Budapest, 1121, Hungary

Location

Sheba Medical Center Hospital - Tel Hashomer

Ramat Gan, Tel Aviv, 52621, Israel

Location

IRCCS Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani

Roma, Rome, 00149, Italy

Location

Ente Ospedaliero Ospedali Galliera

Genova, 16128, Italy

Location

Wojewódzki Specjalistyczny Szpital im. Dr. Władysława Biegańskiego

Lodz, Lódzkie, 91-347, Poland

Location

Hospital da Senhora da Oliveira - Guimarães

Guimarães, Braga District, 4835-044, Portugal

Location

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

Lisbon, Lisbon District, 1649-035, Portugal

Location

Hospital Pedro Hispano

Senhora da Hora, 4464-513, Portugal

Location

Centro Hospitalar de Vila Nova de Gaia/Espinho

Vila Nova de Gaia, 4434-502, Portugal

Location

Hospital Germans Trias i Pujol

Badalona, Barcelona, 08916, Spain

Location

Hospital Universitario Quirónsalud Madrid

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Hospital Alvaro Cunqueiro - Clinico Universitario Vigo

Vigo, Pontevedra, 36213, Spain

Location

Hospital del Mar - Parc de Salut Mar

Barcelona, 08003, Spain

Location

Vall d'Hebron Institut de Recerca

Barcelona, 08035, Spain

Location

Hospital Clinic de Barcelona

Barcelona, 08036, Spain

Location

Hospital San Pedro de Alcantara

Cáceres, 10003, Spain

Location

Hospital Universitario de La Princesa

Madrid, 28006, Spain

Location

Hospital General Universitario Gregorio Marañón

Madrid, 28007, Spain

Location

MD Anderson Cancer Center Madrid

Madrid, 28033, Spain

Location

Hospital Universitario Ramón y Cajal

Madrid, 28034, Spain

Location

Hospital Clínico San Carlos

Madrid, 28040, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario HM Sanchinarro

Madrid, 28050, Spain

Location

Hospital Regional Universitario de Málaga - Hospital General

Málaga, 29010, Spain

Location

Complejo Asistencial Universitario de Salamanca - Hospital Clínico

Salamanca, 37007, Spain

Location

Hospital Universitario Miguel Servet

Zaragoza, 50009, Spain

Location

The Newcastle Upon Tyne Hospitals NHS Foundation Trust

Newcastle upon Tyne, England, NE1 4LP, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, NW1 2BU, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 39182994 DERIVED

MeSH Terms

Conditions

COVID-19

Interventions

plitidepsin

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Clinical Developtment, Department of PharmaMar´s Oncology., Business Unit.
• Organization: Pharma Mar, S.A.

clinicaltrials@pharmamar.com

+34 918466000

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2022
• First Posted: January 30, 2023
• Study Start: April 19, 2023
• Primary Completion: March 19, 2024
• Study Completion: April 19, 2024
• Last Updated: December 2, 2024
• Results First Posted: December 2, 2024

Record last verified: 2024-09

Locations

FR (5); BE (1); IT (2); GE (3); HU (1); PL (1); PT (4); GB (2); ES (18); GR (6); IL (1)