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

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ClinicalTrials.gov Identifier: NCT05705167
Recruitment Status : Terminated (Significant difficulties in the recruitment of patients)
First Posted : January 30, 2023
Last Update Posted : April 26, 2024
Sponsor:
Information provided by (Responsible Party):
PharmaMar

Study Description
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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
COVID-19 Drug: Plitidepsin Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 37 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 19, 2023
Actual Primary Completion Date : March 19, 2024
Actual Study Completion Date : April 19, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 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.
 Drug: Plitidepsin
IV infusion over 60-minutes
No Intervention: 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.


Outcome Measures
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Primary Outcome Measures :
  1. All-cause Mortality Rate [ Time Frame: Day 1 to Day 30 (±2) ]

Secondary Outcome Measures :
  1. 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 [ Time Frame: Day 1 to Day 60 (±3) ]
  2. Time to Sustained End of COVID-related Hospital Care [ Time Frame: Day 1 to Day 60 (±3) ]
  3. Time to Sustained Improvement of Selected COVID-19 Signs/Symptoms. [ Time Frame: Day 1 to Day 60 (±3) ]
  4. Time to Resolution of Selected COVID-19 Signs/Symptoms [ Time Frame: Day 1 to Day 60 (±3) ]
  5. Percentage of Participants in Each Category of the World Health Organization (WHO) Clinical Progression Scale [ Time Frame: Days 4 (±1), 8 (±1), 15 (±1), 30 (±2) and 60 (±3) ]
  6. Percentage of Participants Requiring Oxygen Therapy [ Time Frame: Days 4 (±1), 8 (±1), 15 (±1), 30 (±2) and 60 (±3) ]
  7. Time to Sustained Discontinuation of Oxygen Supplementation [ Time Frame: Day 1 to Day 60 (±3) ]
  8. Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) [ Time Frame: 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)
    • Serious adverse reactions (SARs)
    • Adverse events leading to treatment discontinuation
    • Deaths (related to COVID-19/all)

  9. Number of Participants with a Clinically Relevant/Significant Change from Baseline in Individual Laboratory Parameters [ Time Frame: Baseline to Day 60 (±3) ]
  10. Number of Participants with a Clinically Relevant/Significant Change from Baseline in Individual Vital Signs [ Time Frame: Baseline to Day 60 (±3) ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05705167


Locations
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Sponsors and Collaborators
PharmaMar
More Information
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Responsible Party: PharmaMar
ClinicalTrials.gov Identifier: NCT05705167    
Other Study ID Numbers: AV-APL-B-002-22
2022-002489-34 ( EudraCT Number )
First Posted: January 30, 2023    Key Record Dates
Last Update Posted: April 26, 2024
Last Verified: April 2024

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by PharmaMar:
COVID-19
Plitidepsin
Additional relevant MeSH terms:
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COVID-19
Pneumonia, Viral
Pneumonia
Respiratory Tract Infections
Infections
Virus Diseases
 Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases