Clinical trial NCT05705167: Plitidepsin Versus Control in Immunocompromised Adult Participants With Symptomatic COVID-19 Requiring Hospital Care (NEREIDA)
Official title: A Multicentre, Open Label, Randomised, Controlled, Basket, Pragmatic, Phase II, Clinical and Translational Study to Determine the Efficacy and Safety of Plitidepsin Versus Control in Immunocompromised Adult Patients With Symptomatic COVID-19 Requiring Hospital Care
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID-19
Keywords: COVID-19
Plitidepsin
Lead sponsor: PharmaMar
Sponsor class: INDUSTRY
First posted: 2023-01-30
Enrollment: 37
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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-specific inclusion criteria:

* 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.

Primary outcomes:
measure: One-month All-cause Mortality Rate
timeFrame: Day 1 to Day 30 (±2)
Secondary outcomes:
measure: Time to Confirmed Negativisation in SARS-CoV-2 Antigen Test or Real Time Polymerase Chain Reaction (RT-PCR) Cycle Threshold (Ct) > 30
timeFrame: Day 1 to Day 60 (±3)
measure: Time to Sustained End of COVID-related Hospital Care
timeFrame: Day 1 to Day 60 (±3)
measure: Time to Sustained Improvement and Resolution of Selected COVID-19 Signs/Symptoms
timeFrame: Day 1 to Day 60 (±3)
measure: Number of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale (CPS)
timeFrame: Days 4 (±1), 8 (±1), 15 (±1), 30 (±2), and 60 (±3)
measure: Number of Participants Requiring Oxygen Therapy
timeFrame: Days 4 (±1), 8 (±1), 15 (±1), 30 (±2), and 60 (±3)
measure: Time to Sustained Discontinuation of Oxygen Supplementation
timeFrame: Day 1 to Day 60 (±3)
measure: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)
timeFrame: Day 1 to Day 60 (±3)
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven - Campus Gasthuisberg
state: Flemish Brabant
city: Colmar
country: France
facility: Hôpitaux Civils de Colmar - Centre Hospitalier Louis Pasteur
state: Grand Est
city: Tours
country: France
facility: Centre Hospitalier Régional Universitaire de Tours
state: Indre-et-Loire
city: Bayonne
country: France
facility: Centre Hospitalier de la Côte Basque
state: Pyrénées-Atlantiques
city: Lyon
country: France
facility: Cancer Research Centre of Lyon
state: Rhone-Alpes
city: Strasbourg
country: France
facility: Les Hôpitaux Universitaires de Strasbourg
city: Tbilisi
country: Georgia
facility: The First University Clinic of the Tbilisi State Medical University
city: Tbilisi
country: Georgia
facility: Ltd Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic
city: Tbilisi
country: Georgia
facility: Academician Vakhtang Bochorishvili Clinic
city: Athens
country: Greece
facility: General Hospital of Athens Evangelismos
state: Attica
city: Athens
country: Greece
facility: Laiko General Hospital of Athens
state: Attica
city: Athens
country: Greece
facility: Alexandra General Hospital
state: Attica
city: Athens
country: Greece
facility: University General Hospital Attikon
state: Attica
city: Ioannina
country: Greece
facility: University Hospital of Ioannina
state: Epirus
city: Athens
country: Greece
facility: General Hospital for Thoracic Diseases Sotiria
city: Budapest
country: Hungary
facility: Országos Korányi Pulmonológiai Intézet
city: Ramat Gan
country: Israel
facility: Sheba Medical Center Hospital - Tel Hashomer
state: Tel Aviv
city: Roma
country: Italy
facility: IRCCS Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani
state: Rome
city: Genova
country: Italy
facility: Ente Ospedaliero Ospedali Galliera
city: Łódź
country: Poland
facility: Wojewódzki Specjalistyczny Szpital im. Dr. Władysława Biegańskiego
state: Lódzkie
city: Guimaraes
country: Portugal
facility: Hospital da Senhora da Oliveira - Guimarães
state: Braga
city: Lisbon
country: Portugal
facility: Centro Hospitalar Universitário Lisboa Norte, E.P.E - Hospital De Santa Maria
state: Lisboa
city: Senhora da Hora
country: Portugal
facility: Hospital Pedro Hispano
city: Vila Nova de Gaia
country: Portugal
facility: Centro Hospitalar de Vila Nova de Gaia/Espinho
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Barcelona
city: Pozuelo de Alarcón
country: Spain
facility: Hospital Universitario Quirónsalud Madrid
state: Madrid
city: Vigo
country: Spain
facility: Hospital Alvaro Cunqueiro - Clinico Universitario Vigo
state: Pontevedra
city: Barcelona
country: Spain
facility: Hospital del Mar - Parc de Salut Mar
city: Barcelona
country: Spain
facility: Vall d'Hebron Institut de Recerca
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcantara
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
city: Madrid
country: Spain
facility: MD Anderson Cancer Center Madrid
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Málaga - Hospital General
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca - Hospital Clínico
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet
city: Newcastle Upon Tyne
country: United Kingdom
facility: The Newcastle Upon Tyne Hospitals NHS Foundation Trust
state: England
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
Study officials:
References: