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Trial to Determine the Efficacy/Safety of Plitidepsin vs Control in Patients With Moderate COVID-19 Infection (Neptuno)

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ClinicalTrials.gov Identifier: NCT04784559
Recruitment Status : Recruiting
First Posted : March 5, 2021
Last Update Posted : November 22, 2021
Sponsor:
Information provided by (Responsible Party):
PharmaMar

Brief Summary:
Treatment of patients hospitalised for management of moderate COVID-19 infection

Condition or disease Intervention/treatment Phase
COVID-19 Infection Drug: Plitidepsin Drug: Dexamethasone Drug: Remdesivir Drug: Favipiravir Phase 3

Detailed Description:
This is a multicentre, open-label, controlled Phase 3 study in which adults requiring hospital admission and O2 supplementation for management of moderate COVID-19 infection will be randomised in 1:1:1 to: Plitidepsin 1.5 mg arm, Plitidepsin 2.5 mg arm and Control arm

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 609 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Patients Will be randomised in 1:1:1 to: Plitidepsin 1.5 mg arm, Plitidepsin 2.5 mg arm and Control arm
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3, Multicentre, Randomised, Controlled Trial to Determine the Efficacy and Safety of Two Dose Levels of Plitidepsin Versus Control in Adult Patient Requiring Hospitalisation for Management of Moderate COVID-19 Infection
Actual Study Start Date : June 4, 2021
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2022

Arm Intervention/treatment
Experimental: Plitidepsin 1.5 mg arm

Patients will receive plitidepsin 1.5 mg/day intravenous (IV) combined with dexamethasone phosphate 8 mg/day (equivalent to 6.6 mg dexamethasone base) IV on Days 1 to 3, followed by dexamethasone phosphate 7.2 mg (equivalent to 6 mg/day dexamethasone base) oral administration (PO)/IV from Day 4 and up to a total cumulative dose of 60 mg of dexamethasone base (as per physician judgement according to patient clinical condition and evolution).

The study allows up to a total cumulative dose of 60 mg of dexamethasone base (calculation of the total dose will also include corticosteroids administered within 72 hours before the start of the study treatment and dexamethasone administered as premedication).

Drug: Plitidepsin

Plitidepsin 2 mg powder is provided as a sterile, preservative-free, and white to off-white lyophilised powder/cake comprising 2 mg plitidepsin and 100 mg mannitol in a single-dose, 10 mL clear type 1 glass vial.

Solvent for plitidepsin is provided as a sterile, preservative-free, clear, slightly viscous aqueous liquid (4 mL) containing 0.15 mL macrogolglycerol ricinoleate and 0.15 mL/mL ethanol in a single-dose type 1 clear glass ampoule.

For administration, vial contents are reconstituted by addition of 4 mL of solvent for plitidepsin to obtain a slightly yellowish solution containing 0.5 mg/mL plitidepsin with mannitol, macrogolglycerol ricinoleate and ethanol excipients. The required amount of plitidepsin reconstituted solution is added to an IV bag containing 0.9% sodium chloride injection or 5% glucose for injection and administered as an intravenous infusion over 60 minutes.


Drug: Dexamethasone
Detailed information about the formulation, packaging and labelling, storage, and manufacturer is provided in the current country-specific product information. The summary of product characteristics (SmPC) and/or leaflet provides detailed product information for investigators in the European Union and/or in other regions.

Experimental: Plitidepsin 2.5 mg arm

Patients will receive plitidepsin 2.5 mg/day intravenous (IV) combined with dexamethasone phosphate 8 mg/day (equivalent to 6.6 mg dexamethasone base) IV on Days 1 to 3, followed by dexamethasone phosphate 7.2 mg (equivalent to 6 mg/day dexamethasone base) from Day 4 and up to a total cumulative dose of 60 mg of dexamethasone base (as per physician judgement according to patient clinical condition and evolution).

The study allows up to a total cumulative dose of 60 mg of dexamethasone base (calculation of the total dose will also include corticosteroids administered within 72 hours before the start of the study treatment and dexamethasone administered as premedication).

Drug: Plitidepsin

Plitidepsin 2 mg powder is provided as a sterile, preservative-free, and white to off-white lyophilised powder/cake comprising 2 mg plitidepsin and 100 mg mannitol in a single-dose, 10 mL clear type 1 glass vial.

Solvent for plitidepsin is provided as a sterile, preservative-free, clear, slightly viscous aqueous liquid (4 mL) containing 0.15 mL macrogolglycerol ricinoleate and 0.15 mL/mL ethanol in a single-dose type 1 clear glass ampoule.

For administration, vial contents are reconstituted by addition of 4 mL of solvent for plitidepsin to obtain a slightly yellowish solution containing 0.5 mg/mL plitidepsin with mannitol, macrogolglycerol ricinoleate and ethanol excipients. The required amount of plitidepsin reconstituted solution is added to an IV bag containing 0.9% sodium chloride injection or 5% glucose for injection and administered as an intravenous infusion over 60 minutes.


Drug: Dexamethasone
Detailed information about the formulation, packaging and labelling, storage, and manufacturer is provided in the current country-specific product information. The summary of product characteristics (SmPC) and/or leaflet provides detailed product information for investigators in the European Union and/or in other regions.

Active Comparator: Control arm

Dexamethasone phosphate 8 mg/day (equivalent to 6.6 mg dexamethasone base) IV on Days 1 to 3, followed by dexamethasone phosphate 7.2 mg (equivalent to 6 mg/day dexamethasone base) from Day 4 and up to a total cumulative dose of 60 mg of dexamethasone base (as per physician judgement according to patient clinical condition and evolution). Per local treatment guidelines, patients may receive a regulatory approved antiviral treatment, such as remdesivir (200 mg IV on Day 1 followed by 100 mg/day IV on Days 2 to 5) or favipiravir (1600 mg twice daily [BID] PO on Day 1, followed by 600 mg BID PO daily for 2 to 5 days). Antiviral to be used per approved product information in each country, different dosages could be used.

The study allows up to a total cumulative dose of 60 mg of dexamethasone base (calculation of the total dose will also include corticosteroids administered within 72 hours before the start of the study treatment and dexamethasone administered as premedication).

Drug: Dexamethasone
Detailed information about the formulation, packaging and labelling, storage, and manufacturer is provided in the current country-specific product information. The summary of product characteristics (SmPC) and/or leaflet provides detailed product information for investigators in the European Union and/or in other regions.

Drug: Remdesivir
Detailed information about the formulation, packaging and labelling, storage, and manufacturer is provided in the current country-specific product information. The summary of product characteristics (SmPC) and/or leaflet provides detailed product information for investigators in the European Union and/or in other regions.

Drug: Favipiravir
Detailed information about the formulation, packaging and labelling, storage, and manufacturer is provided in the current country-specific product information. The summary of product characteristics (SmPC) and/or leaflet provides detailed product information for investigators in the European Union and/or in other regions.




Primary Outcome Measures :
  1. Percentage of patients who achieve complete recovery: [ Time Frame: Day 8 (±1) ]

    (i) meeting categories 0 to 2 on 11-point World Health Organization (WHO) Clinical Progression Scale, (ii) Barthel Index >90/100 at the time of discharge, and (iii) with no re-admission for COVID-19-related signs or symptoms through Day 31.

    11-category WHO Clinical Progression Scale: 0. uninfected, no viral RNA detected; 1. asymptomatic, viral RNA detected and 2; symptomatic, independent



Secondary Outcome Measures :
  1. Time to complete recovery [ Time Frame: From administration date to Day 31 ]
  2. Clinical status assessed by 11-category WHO Clinical Progression Scale: [ Time Frame: Once daily while the patient is hospitalized, Day 8 (±1), 4, 15, 31 ]

    0: uninfected, no viral RNA detected

    1. asymptomatic, viral RNA detected
    2. symptomatic, independent
    3. symptomatic, assistance needed
    4. hospitalised, no oxygen therapy (if hospitalised for isolation only, record status as for ambulatory patient)
    5. hospitalised, oxygen by mask or nasal prongs
    6. hospitalised, oxygen by noninvasive ventilation (NIV) or high flow
    7. intubation and mechanical ventilation. pO2/FIO2 ≥150 or SpO2/FIO2 ≥200
    8. mechanical ventilation pO2/FIO2 <150 (SpO2/FIO2 <200) or vasopressors
    9. mechanical ventilation pO2/FIO2 <150 and vasopressors, dialysis, or ECMO
    10. dead

  3. Proportion of patients with treatment-emergent adverse events (TEAEs) [ Time Frame: From administration date to Day 31 ]
  4. Proportion of patients with Grade ≥3 TEAEs [ Time Frame: From administration date to Day 31 ]
  5. Proportion of patients with serious adverse events (SAEs) [ Time Frame: From administration date to Day 31 ]
  6. Proportion of patients with serious adverse reactions (SARs) [ Time Frame: From administration date to Day 31 ]
  7. Proportion of patients with adverse events (AEs) of special interest [ Time Frame: From administration date to Day 31 ]
  8. Number and severity of treatment emergent adverse events as per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 criteria (CTCAE v5.0) [ Time Frame: From administration date to Day 31 ]
  9. Proportion of patients requiring re-admission for COVID-19 signs or symptoms [ Time Frame: From administration date to Day 31 ]
  10. Duration of oxygen therapy (in days) [ Time Frame: From administration date to day 31 ]
  11. Proportion of patients requiring high-flow oxygen [ Time Frame: Days 4, 8, 15, and 31 ]
  12. Proportion of patients requiring noninvasive mechanical ventilation [ Time Frame: Days 4, 8, 15, and 31 ]
  13. Proportion of patients requiring invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) [ Time Frame: Days 4, 8, 15, and 31 ]
  14. Proportion of patients requiring admission to Intensive Care Unit (ICU) [ Time Frame: Days 4, 8, 15, and 31 ]
  15. Duration of hospitalization in ICU [ Time Frame: From administration date to Day 31 ]
  16. Proportion of patients receiving subsequent antiviral therapies or immunomodulatory drugs [ Time Frame: Days 4, 8, 15, and 31 ]
  17. Proportion of patients with nosocomial infection [ Time Frame: From administration date to Day 31 ]
  18. Mortality [ Time Frame: Days 4, 8, 15, and 31 ]
  19. Change in SARS-CoV-2 viral, as measured by quantitative polymerase chain reaction (qPCR) from samples of oro-nasopharyngeal exudate [ Time Frame: Day 8(+/- 1) ]
  20. Proportion of patients with undetectable SARS-CoV-2 viral load, as measured by qPCR from samples of oro-nasopharyngeal exudate [ Time Frame: Day 8(+/- 1) ]
  21. Change in inflammatory biomarker: C-reactive protein (CRP) [ Time Frame: Days 1, 2, 3, 4, 8, and 31 ]
  22. Change in inflammatory biomarker: ferritin [ Time Frame: Days 1, 2, 3, 4, 8, and 31 ]
  23. Change in inflammatory biomarker: IL-6, IL-1β, IL-10 [ Time Frame: Days 1, 2, 3, 4, 8, and 31 ]
  24. Change in inflammatory biomarker: tumour necrosis factor alpha (TNFα) [ Time Frame: Days 1, 2, 3, 4, 8, and 31 ]
  25. Proportion of patients with serologic response anti-SARS-CoV-2 [ Time Frame: Day 1 and 31 ]
  26. Time to therapy intensification (WHO >6 [intubation] or initiation of other antiviral/immunomodulating agent) [ Time Frame: From administration date to Day 31 ]
  27. Percentage of patients requiring increased oxygen therapy on study [ Time Frame: From administration date to Day 31 ]

Other Outcome Measures:
  1. Incidence of treatment emergent adverse events (TEAEs), Grade ≥3 TEAEs, serious adverse events (SAEs), deaths, TEAEs leading to premature discontinuation of study drug and adverse events (AEs) of special interest [ Time Frame: From administration date to Day 31 ]
  2. Change from baseline in clinical chemistry parameter: alanine transaminase (ALT) [U/L] [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  3. Change from baseline in clinical chemistry parameter: aspartate transaminase (AST) [U/L] [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  4. Change from baseline in clinical chemistry parameter: alkaline phosphatase [U/L] [ Time Frame: Days 1, 2, 3, 4, 8, and 31 ]
  5. Change from baseline in clinical chemistry parameter: gamma glutamyl transferase (GGT) [U/L] [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  6. Change from baseline in clinical chemistry parameter: lactate dehydrogenase (LDH) [U/L] [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  7. Change from baseline in clinical chemistry parameter: total bilirubin [mg/dL] [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  8. Change from baseline in clinical chemistry parameter: direct bilirubin [mg/dL] [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  9. Change from baseline in clinical chemistry parameter: lipase [U/L] [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  10. Change from baseline in clinical chemistry parameter: amylase [U/L] [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  11. Change from baseline in clinical chemistry parameter: glucose (fasting) (mg/dL) [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  12. Change from baseline in clinical chemistry parameter: sodium [mEq/L] [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  13. Change from baseline in clinical chemistry parameter: potassium [mEq/L] [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  14. Change from baseline in clinical chemistry parameter: calcium (albumin adjusted calculation) [mEq/L] [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  15. Change from baseline in clinical chemistry parameter: magnesium [mEq/L] [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  16. Change from baseline in clinical chemistry parameter: blood urea nitrogen (BUN) [mg/dL] [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  17. Change from baseline in clinical chemistry parameter: creatinine [mg/dL] [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  18. Change from baseline in clinical chemistry parameter: calculated creatinine clearance (Cockcroft-Gault equation) [ml/min] [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  19. Change from baseline in clinical chemistry parameter: albumin [g/dL] [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  20. Change from baseline in clinical chemistry parameter: creatine-phosphokinase (CPK) [U/L] [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  21. Change from baseline in Troponin (I or T according to local practice for screening) [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  22. Change from baseline in Troponin T (high sensitivity) [ Time Frame: Screening (Day 0-1), Days 1, 8, and 31 ]
  23. Change from baseline in N-terminal pro b-type natriuretic peptide (NT-pro BNP) [ Time Frame: Screening (Day 0-1), Days 1, 8, and 31 ]
  24. Change from baseline in Procalcitonin [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  25. Change from baseline in coagulation: D dimer [ Time Frame: Days 1, 2, 3, 4, 8, and 31 ]
  26. Change from baseline in serological SARS CoV 2 testing: immunoglobulin [Ig]G) [ Time Frame: Day 1 and 31(+/- 3) ]
  27. Change from baseline in hematology laboratory parameter: red blood cell (RBC) [cells10^6/µL] [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  28. Change from baseline in hematology laboratory parameter: haemoglobin [g/dL] [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  29. Change from baseline in hematology laboratory parameter: haematocrit [%] [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  30. Change from baseline in hematology laboratory parameter: white blood cell (WBC) with differential [cells10^3/µL] [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  31. Change from baseline in hematology laboratory parameter: platelet count [cells10^3/µL] [ Time Frame: Screening (Day 0-1), Days 1, 2, 3, 4, 8, and 31 ]
  32. Change from baseline in vital sign: temperature [°C or °F] [ Time Frame: Screening (Day 0-1), Once daily while the patient is hospitalized, and on Days 8 and 31 ]
  33. Change from baseline in vital sign: sitting blood pressure [mmHg] [ Time Frame: Screening (Day 0-1), Once daily while the patient is hospitalized, and on Days 8 and 31 ]
  34. Change from baseline in vital sign: heart rate [beats per minute] [ Time Frame: Screening (Day 0-1), Once daily while the patient is hospitalized, and on Days 8 and 31 ]
  35. Change from baseline in vital sign: respiratory rate [breaths per minute] [ Time Frame: Screening (Day 0-1), Once daily while the patient is hospitalized, and on Days 8 and 31 ]
  36. Change from baseline in vital sign: saturation of oxygen (SpO2) at room air [%]by pulse oximetry or arterial blood gas analyses and its respective FiO2 [%] [ Time Frame: Screening (Day 0-1), Once daily while the patient is hospitalized, and on Days 8 and 31 ]
  37. Change from baseline in electrocardiogram (ECG) findings: QTcF prolongation [ Time Frame: Screening (Day 0-1), Day, 1, Day 3 (postinfusion) and Day 31 ]
  38. Change from baseline in electrocardiogram (ECG) findings: any QTcF values >500 msec [ Time Frame: Screening (Day 0-1), Day, 1, Day 3 (postinfusion) and Day 31 ]
  39. Change from baseline in electrocardiogram (ECG) findings: QTcF interval >30 msec [ Time Frame: Screening (Day 0-1), Day, 1, Day 3 (postinfusion) and Day 31 ]
  40. Substudy only: Change from baseline in electrocardiogram (ECG) findings: heart rate [ Time Frame: 0, 1, 2.5, 5, 24, 25, 26.5, 29, 48, and 49 hours ]
  41. Substudy only: Change from baseline in ECG findings: QTc [ Time Frame: 0, 1, 2.5, 5, 24, 25, 26.5, 29, 48 and 49 hours ]
  42. Substudy only: Change from baseline in ECG findings: QRS [ Time Frame: 0, 1, 2.5, 5, 24, 25, 26.5, 29, 48, and 49 hours ]
  43. Substudy only: Change from baseline in ECG findings: waveform morphology-related measurements [ Time Frame: 0, 1, 2.5, 5, 24, 25, 26.5, 29, 48, and 49 hours ]
  44. Substudy only: Change from baseline in ECG findings: QTc for whole blood concentrations of plitidepsin (ng/ml) [ Time Frame: 0, 1, 2.5, 5, 24, 25, 26.5, 29, 48, and 49 hours ]
  45. Substudy only: Whole blood clearance of plitidepsin [ Time Frame: 0, 1, 2.5, 5, 24, 25, 26.5, 29, 48, 49 and 72 hours ]
  46. Substudy only: Whole blood area under curve (AUC) of plitidepsin [ Time Frame: 0, 1, 2.5, 5, 24, 25, 26.5, 29, 48, 49 and 72 hours ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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:

  1. Signed informed consent obtained prior to initiation of any study-specific procedures and study treatment
  2. Documented diagnosis of SARS-CoV-2 infection, determined by either qualitative polymerase chain reaction (PCR) or antigen test by local laboratory, from oro nasopharyngeal exudate collected no more than 72 hours prior to study treatment on Day 1
  3. Patient meets category 5 on the 11-point WHO Clinical Progression Scale: requires hospitalization and oxygen by mask or nasal prongs/cannula
  4. A maximum of 10 days from onset of COVID-19 symptoms to initiation of study treatment on Day 1
  5. Male or female aged ≥18 years
  6. Adequate bone marrow, liver, kidney, and metabolic function, defined by the following tests performed at local laboratory:

    • Absolute neutrophil count ≥1000/mm^3 (1.0 x 10^9/L)
    • Lymphocyte count ≥500/mm^3 (0.5 x 10^9/L)
    • Platelet count ≥100 000/mm^3 (100 x 10^9/L)
    • Haemoglobin >9.0 g/dL
    • Alanine transaminase (ALT), aspartate transaminase (AST) ≤3 x upper limit of normal (ULN)
    • Serum bilirubin ≤1 x ULN
    • Calculated creatinine clearance ≥30 mL/min (Cockcroft and Gault formula)
    • Creatine phosphokinase ≤2.5 x ULN except if the patient has had recent (ie, in the last week) shivering episodes or trauma. In that case, the level of creatine phosphokinase (CPK) should be ≤5 x ULN).
  7. Agree not to participate in another interventional clinical trial through Day 31
  8. Females of reproductive capacity must have a negative serum or urine pregnancy test by local laboratory at study enrolment and must be non-lactating
  9. Females and males with partners of child-bearing potential must use effective contraception while on study treatment and for 6 months after last dose of plitidepsin. Patients in the control arm must use effective contraception at the time indicated in the approved product information (summary of product characteristics [SmPC] or leaflet). If no information is available in the approved product information, patients in the control arm must use effective contraception for at least one week after the study completion or the time indicated based on the investigator's discretion.

Exclusion Criteria:

  1. Subjects with a pre-baseline (ie, in the prior month) impairment in general health condition for whatever reason except COVID 19, requiring either assistance for daily living activities (Barthel index <90/100) or chronic oxygen therapy
  2. Having received treatment for COVID 19 in another clinical trial in the prior 4 weeks, except documented allocation in a placebo arm.
  3. Evidence of respiratory failure at the time of randomisation, based on resource utilisation requiring at least one of the following: endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula, noninvasive positive pressure ventilation, ECMO, or clinical diagnosis of respiratory failure (ie, clinical need for one of the preceding therapies, but preceding therapies not able to be administered in setting of resource limitation)
  4. Patients with severe COVID 19, meeting score >5 on the 11 point WHO Clinical Progression Scale or presenting during the screening any of clinical signs indicative of severe systemic illness, such as respiratory rate ≥30 per minute, heart rate ≥125 per minute, or PaO2/FiO2 <300
  5. Patients receiving treatment with antiviral therapy against SARS-CoV-2 (either small molecules or antibodies, convalescent plasma, monoclonal antibodies, IL 6 receptor inhibitor, or immunomodulatory drugs) within 2 weeks before enrolment. Prior administration of dexamethasone or equivalent glucocorticoid might be acceptable if:

    1. The total daily dose is not higher than 6 mg of dexamethasone base (equivalent to dexamethasone phosphate 7.2 mg/day) or equivalent glucocorticoid
    2. The duration of the treatment does not exceed 72 hours prior to study treatment Day 1
  6. History of live vaccination within the last 4 weeks prior to study enrolment. Regulatory approved, nonreplicative viral vector based vaccines are allowed if given not earlier than 1 week previous to Day 1.
  7. Patients receiving treatment with chloroquine or derivatives within 8 weeks before enrolment or during the study
  8. Patients receiving treatment with strong cytochrome P450 3A4 ( CYP3A4) inhibitors or inducers
  9. Viral illness (other than COVID 19) requiring therapy, except for patients with treated and adequately controlled (undetectable) human immunodeficiency virus infection
  10. Patients with uncontrolled known primary or secondary immunodeficiency, including chronic treatment with glucocorticoids (ie, prednisone at a daily dose of >10 mg for >1 month, or other glucocorticoid at equipotent dose)
  11. Any of the following cardiac conditions or risk factors:

    • Sinus bradycardia (<50 beats/min), sinus nodal dysfunction (sick sinus disease), atrioventricular block of any degree (PR >200 msec), or any other bradyarrhythmia (<50 beats/min), except for patients with permanent pacemakers;
    • Cardiac infarction, cardiac surgery or cardiac insufficiency episode within the last 6 months;
    • Known abnormal value of left ventricular ejection fraction (LVEF < LLN), unless documented confirmation of recovery (LVEF > LLN) in the previous month;
    • QT interval corrected using Fridericia's formula (QTcF) >450 msec for males or >470 msec for females, based on triplicate 12-lead ECG at screening
    • History of known congenital or acquired QT prolongation
    • Uncorrected hypokalaemia, hypocalcaemia (adjusted), and/or hypomagnesemia at screening
    • Concomitant treatments with drugs known to be associated with a risk of QT prolongation or cardiac arrhythmia
    • Troponin test performed at local laboratory > 1.5 x ULN
  12. Pre-existing neuropathies of any type Grade ≥2 according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0
  13. Hypersensitivity to the active ingredient or any of the excipients (mannitol, macrogolglycerol hydroxystearate, and ethanol)
  14. Females who are pregnant (negative serum or urine pregnancy test required for all females of child-bearing potential at screening) or breast feeding
  15. Females and males with partners of child-bearing potential (females who are not surgically sterile or postmenopausal defined as amenorrhoea for >12 months) who are not using at least 1 protocol-specified method of contraception
  16. Any other clinically significant medical condition or laboratory abnormality that, in the opinion of the investigator, would jeopardise the safety of the patient or potentially impact patient compliance or the safety/efficacy observations in the study.

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): NCT04784559


Contacts
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Contact: José Jimeno Doñaque, MD, PhD +34918466000 clinicaltrials@pharmamar.com

Locations
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Sponsors and Collaborators
PharmaMar
Investigators
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Principal Investigator: José Jimeno Doñaque, MD, PhD PharmaMar
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Responsible Party: PharmaMar
ClinicalTrials.gov Identifier: NCT04784559    
Other Study ID Numbers: APL-D-003-20
2020-005951-19 ( EudraCT Number )
First Posted: March 5, 2021    Key Record Dates
Last Update Posted: November 22, 2021
Last Verified: November 2021

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Remdesivir
Infections
Communicable Diseases
COVID-19
Disease Attributes
Pathologic Processes
Respiratory Tract Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases
Favipiravir
Dexamethasone
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antimetabolites