NEREIDA: Plitidepsin Versus Control in Immunocompromised Adult Participants With Symptomatic COVID-19 Requiring Hospital Care
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Plitidepsin 2.5 mg Best available supportive care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) and plitidepsin (administered as a 1-hour intravenous (IV) infusion, daily 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 hematopoietic 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
IV infusion over 1-hour
|
| No Intervention: Control Best available supportive care (as per applicable local, institutional, national, supranational COVID-19 treatment guidelines) will be administered to participants of the following groups: Group 1 - Participants receiving immune-suppression due to hematopoietic or organ transplantation. Group 2 - Participants receiving B-cell depleting therapies. Group 3 - Participants receiving other immune-suppressive therapies. |
Outcome Measures
Primary Outcome Measures
- All-cause Mortality Rate [Day 1 to Day 30 (±2)]
Secondary Outcome Measures
- 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)]
- Time to Sustained End of COVID-related Hospital Care [Day 1 to Day 60 (±3)]
- Time to Sustained Improvement of Selected COVID-19 Signs/Symptoms. [Day 1 to Day 60 (±3)]
- Time to Resolution of Selected COVID-19 Signs/Symptoms [Day 1 to Day 60 (±3)]
- 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)]
- Percentage of Participants Requiring Oxygen Therapy [Days 4 (±1), 8 (±1), 15 (±1), 30 (±2) and 60 (±3)]
- Time to Sustained Discontinuation of Oxygen Supplementation [Day 1 to Day 60 (±3)]
- Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) [Day 1 to Day 60 (±3)]
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) Adverse events leading to treatment discontinuation Deaths (related to COVID-19/all)
- Number of Participants with a Clinically Relevant/Significant Change from Baseline in Individual Laboratory Parameters [Baseline to Day 60 (±3)]
- Number of Participants with a Clinically Relevant/Significant Change from Baseline in Individual Vital Signs [Baseline to Day 60 (±3)]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Signed informed consent obtained prior to initiation of any study-specific procedures and study treatment.
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Participant aged ≥18 years.
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Participant diagnosed COVID-19, with the following characteristics:
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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.
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Presence of any of the selected signs/symptom listed in the COVID-19 signs/symptoms checklist within the last 24 hours.
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Participant already admitted or requiring hospital care for symptomatic COVID-19, for which at least one antiviral has failed or cannot be used.
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Adequate bone marrow, liver, kidney, and metabolic function, defined by the following tests performed at local laboratory:
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Absolute neutrophil count ≥500/mm^3 (0.5 x 109/L).
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Platelet count ≥ 50 000/mm3 (50 x 109/L).
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Alanine transaminase (ALT) ≤3 x upper limit of normal (ULN) (≤5 x ULN if preexistent liver involvement by the underlying disease).
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Serum bilirubin ≤1.5 x ULN (or direct bilirubin <1.5 x ULN when total bilirubin is above ULN).
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Estimated glomerular filtration rate ≥30 mL/min (CKD-EPI Creatinine Equation [2021]).
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Females of childbearing potential must have a negative serum or urine pregnancy test by local laboratory at screening and must be non-lactating.
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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:
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Group 1 - Patients receiving, within the last 30 days, immune-suppressive therapy due to haematopoietic or organ transplantation.
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Group 2 - Participants receiving B-cell depleting therapies within the last 3 months.
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Group 3 - Participants receiving, within the last 30 days, other immune-suppressive therapies.
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Group 4 - Other situations with immunodeficiency.
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Primary immune deficiencies.
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Human immunodeficiency virus (HIV) infection, with CD4^+ T lymphocyte < 200 cells/μL in the last month.
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Radiation therapy within the last 3 months- requires documentation of ALC < 500 cells/μL.
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Haematological neoplasia or myelodysplasia not currently receiving any therapy.
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Other situations with a documentation of ALC < 500 cells/μL.
Exclusion Criteria:
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Evidence of critical illness.
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Any of the following cardiac conditions or risk factors:
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Cardiac infarction or cardiac surgery episode within the last month.
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History of known congenital QT prolongation.
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Known structural cardiomyopathy with abnormal left ventricular ejection fraction (LVEF) (<50%).
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Current clinical evidence of heart failure or acute cardiac ischaemia (New York Heart Association (NYHA) class III-IV).
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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.
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Females who are pregnant or breast-feeding.
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Females and males with partners of childbearing potential who are not using at least 1 protocol-specified method of contraception.
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Any situation currently requiring increasing needs of immune suppressive agents.
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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.
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Participation in another clinical study involving an investigational drug within 30 days prior to screening.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Centre Léon Bérard | Lyon | France | 69008 | |
| 2 | Országos Korányi Pulmonológiai Intézet | Budapest | Hungary | 1121 | |
| 3 | Wojewódzki Specjalistyczny Szpital im. Dr. Władysława Biegańskiego | Łódź | Poland | 91-347 |
Sponsors and Collaborators
- PharmaMar
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AV-APL-B-002-22
- 2022-002489-34