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

COVID-19 Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05705167
• Other study ID #: AV-APL-B-002-22
• Secondary ID: 2022-002489-34
• Status: Terminated
• Phase: Phase 2
• Start date: April 19, 2023
• Est. completion date: April 19, 2024

Study information

• Verified date: April 2024
• Source: PharmaMar
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 37
• Est. completion date: April 19, 2024
• Est. primary completion date: March 19, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• Plitidepsin
IV infusion over 60-minutes

Locations

Country	Name	City	State
Belgium	Universitair Ziekenhuis Leuven - Campus Gasthuisberg	Leuven	Flemish Brabant
France	Centre Hospitalier de la Côte Basque	Bayonne	Pyrénées-Atlantiques
France	Hôpitaux Civils de Colmar - Centre Hospitalier Louis Pasteur	Colmar	Grand Est
France	Cancer Research Centre of Lyon	Lyon	Rhone-Alpes
France	Les Hôpitaux Universitaires de Strasbourg	Strasbourg
France	Centre Hospitalier Régional Universitaire de Tours	Tours	Indre-et-Loire
Georgia	Academician Vakhtang Bochorishvili Clinic	Tbilisi
Georgia	Ltd Tbilisi State Medical University and Ingorokva High Medical Technology University Clinic	Tbilisi
Georgia	The First University Clinic of the Tbilisi State Medical University	Tbilisi
Greece	Alexandra General Hospital	Athens	Attica
Greece	General Hospital for Thoracic Diseases Sotiria	Athens
Greece	General Hospital of Athens Evangelismos	Athens	Attica
Greece	Laiko General Hospital of Athens	Athens	Attica
Greece	University General Hospital Attikon	Athens	Attica
Greece	University Hospital of Ioannina	Ioannina	Epirus
Hungary	Országos Korányi Pulmonológiai Intézet	Budapest
Israel	Sheba Medical Center Hospital - Tel Hashomer	Ramat Gan	Tel Aviv
Italy	Ente Ospedaliero Ospedali Galliera	Genova
Italy	IRCCS Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani	Roma	Rome
Poland	Wojewódzki Specjalistyczny Szpital im. Dr. Wladyslawa Bieganskiego	Lódz	Lódzkie
Portugal	Hospital da Senhora da Oliveira - Guimarães	Guimaraes	Braga
Portugal	Centro Hospitalar Universitário Lisboa Norte, E.P.E - Hospital De Santa Maria	Lisbon	Lisboa
Portugal	Hospital Pedro Hispano	Senhora da Hora
Portugal	Centro Hospitalar de Vila Nova de Gaia/Espinho	Vila Nova de Gaia
Spain	Hospital Germans Trias i Pujol	Badalona	Barcelona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital del Mar - Parc de Salut Mar	Barcelona
Spain	Vall d'Hebron Institut de Recerca	Barcelona
Spain	Hospital San Pedro de Alcantara	Cáceres
Spain	Hospital Clínico San Carlos	Madrid
Spain	Hospital General Universitario Gregorio Marañón	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario de La Princesa	Madrid
Spain	Hospital Universitario Fundación Jiménez Díaz	Madrid
Spain	Hospital Universitario HM Sanchinarro	Madrid
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	MD Anderson Cancer Center Madrid	Madrid
Spain	Hospital Regional Universitario de Málaga - Hospital General	Málaga
Spain	Hospital Universitario Quirónsalud Madrid	Pozuelo de Alarcón	Madrid
Spain	Complejo Asistencial Universitario de Salamanca - Hospital Clínico	Salamanca
Spain	Hospital Alvaro Cunqueiro - Clinico Universitario Vigo	Vigo	Pontevedra
Spain	Hospital Universitario Miguel Servet	Zaragoza
United Kingdom	The Newcastle Upon Tyne Hospitals NHS Foundation Trust	Newcastle Upon Tyne	England

Sponsors (1)

Lead Sponsor	Collaborator
PharmaMar

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	All-cause Mortality Rate		Day 1 to Day 30 (±2)
Secondary	Key Secondary Outcome Measure: 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)
Secondary	Time to Sustained End of COVID-related Hospital Care		Day 1 to Day 60 (±3)
Secondary	Time to Sustained Improvement of Selected COVID-19 Signs/Symptoms.		Day 1 to Day 60 (±3)
Secondary	Time to Resolution of Selected COVID-19 Signs/Symptoms		Day 1 to Day 60 (±3)
Secondary	Percentage of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale		Days 4 (±1), 8 (±1), 15 (±1), 30 (±2) and 60 (±3)
Secondary	Percentage of Participants Requiring Oxygen Therapy		Days 4 (±1), 8 (±1), 15 (±1), 30 (±2) and 60 (±3)
Secondary	Time to Sustained Discontinuation of Oxygen Supplementation		Day 1 to Day 60 (±3)
Secondary	Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)	Frequency of the following events (all-cause and drug-related) are included: TEAEs; TEAEs = grade 3 according to the National Cancer Institute [NCI]-Common Terminology Criteria for adverse events (CTCAE v.5.0); Adverse events of special interest (AESIs); Serious adverse events (SAEs); Serious adverse reactions (SARs); Adverse events leading to treatment discontinuation; Deaths (related to COVID-19/all)	Day 1 to Day 60 (±3)
Secondary	Number of Participants with a Clinically Relevant/Significant Change from Baseline in Individual Laboratory Parameters		Baseline to Day 60 (±3)
Secondary	Number of Participants with a Clinically Relevant/Significant Change from Baseline in Individual Vital Signs		Baseline to Day 60 (±3)