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 (Neptuno)

  • STATUS
    Recruiting
  • days left to enroll
    30
  • participants needed
    609
  • sponsor
    PharmaMar
Updated on 27 October 2022

Summary

Treatment of patients hospitalised for management of moderate COVID-19 infection

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

Details
Condition COVID-19 Infection
Treatment Dexamethasone, Plitidepsin, Favipiravir, Remdesivir
Clinical Study IdentifierNCT04784559
SponsorPharmaMar
Last Modified on27 October 2022

Eligibility

Yes No Not Sure

Inclusion Criteria

Signed informed consent obtained prior to initiation of any study-specific procedures and study treatment
Documented diagnosis of SARS-CoV-2 infection, determined by either qualitative polymerase chain reaction (PCR), antigen test by local laboratory, or any other validated method approved by the local health authority, from appropriate biological samples collected no more than 72 hours prior to study treatment on Day 1
Patient meets category 5 on the 11-point WHO Clinical Progression Scale: requires hospitalisation and oxygen by mask or nasal prongs/cannula
A maximum of 14 days from onset of COVID-19 symptoms to initiation of study treatment on Day 1
Male or female aged ≥18 years
Absolute neutrophil count ≥500/mm^3 (0.5 x 10^9/L)
Platelet count ≥75,000/mm^3 (75 x 10^9/L)
Adequate bone marrow, liver, kidney, and metabolic function, defined by the following tests performed at local laboratory
Serum bilirubin ≤1 x ULN (or direct bilirubin <1 x ULN when total bilirubin is above ULN)
Alanine transaminase (ALT), aspartate transaminase (AST) ≤3 x upper limit of normal (ULN)
Calculated creatinine clearance ≥30 mL/min (Cockcroft-Gault equation)
Creatine phosphokinase (CPK) ≤2.5 x ULN except if the patient has had recent (i.e., in the last week) shivering episodes or trauma. In that case, the level of CPK should be ≤5 x ULN
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 during 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
Females of reproductive capacity must have a negative serum or urine pregnancy test by local laboratory at study enrolment and must be non-lactating
Agree not to participate in another interventional clinical trial through Day 31

Exclusion Criteria

Subjects with a pre-baseline (i.e., in the month preceding the current COVID-19 infection) impairment in general health condition for whatever reason except COVID-19, with a severe dependency for daily living activities (Barthel index ≤ 60/100) or chronic oxygen therapy
Having received treatment for COVID-19 in another clinical trial in the prior 4 weeks, except documented allocation in a placebo arm
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, non-invasive positive pressure ventilation, ECMO, or clinical diagnosis of respiratory failure (i.e., clinical need for one of the aforementioned therapies, which could not be administered in a resource-limited setting)
Patients with severe COVID-19, meeting score >5 on the 11-point WHO Clinical Progression Scale or presenting, after an initial stabilisation prior to randomisation, 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\. In case a direct measure of PaO2 has not been obtained, it should be imputed according to a referenced formula. For sites located over 1000 m above sea level, PaO2/FiO2 ratio will be adjusted
Patients receiving, at randomisation, treatment with antiviral therapy against SARS-CoV-2 or requiring anti-inflammatory/immunomodulating drugs beyond glucocorticoids with the exceptions listed below
Prior administration of dexamethasone or equivalent glucocorticoid might be acceptable if
The total daily dose is not higher than 10 mg of dexamethasone phosphate (equivalent to dexamethasone base 8.25 mg/day) or equivalent glucocorticoids
The duration of the treatment does not exceed 72 hours prior to study treatment Day 1
Prior administration of dexamethasone or equivalent glucocorticoid might be
acceptable if
The total daily dose is not higher than 10 mg of dexamethasone phosphate (equivalent to dexamethasone base 8.25 mg/day) or equivalent glucocorticoids
The duration of the treatment does not exceed 72 hours prior to study treatment Day 1
Prior administration of an antiviral might be acceptable in the following
circumstances
For small molecules (e.g., remdesivir, molnupiravir, nirmaltrevir/ritonavir), they must have been given for an earlier stage of the disease, outside a clinical trial, and there should be a documentation of objective clinical deterioration plus evidence of persisting positivity for SARS-CoV-2 in appropriate biological samples. Last dose of previous antiviral drugs should have been administered at least 24 h before randomisation
Any of the following cardiac conditions or risk factors
For antiviral monoclonal antibodies, they must have been given for an earlier stage of the disease (including pre-exposure prophylaxis), outside a clinical trial, and there should be a documentation of objective clinical deterioration plus evidence of persisting positivity for SARS-CoV-2 in appropriate biological samples. Last dose of antiviral monoclonal antibodies should have been administered at least 1 week before randomisation
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
Patients receiving treatment with chloroquine or derivatives within 8 weeks before
Cardiac infarction, cardiac surgery or cardiac insufficiency episode within the last 6 months
enrolment or during the study
Patients receiving treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers
Viral illness (other than COVID-19) requiring therapy, except for patients with treated and adequately controlled (undetectable) human immunodeficiency virus infection
History of known congenital or acquired QT prolongation
Patients with uncontrolled known primary or secondary immunodeficiency, including chronic treatment with glucocorticoids (i.e., prednisone at a daily dose of >10 mg for >1 month, or another glucocorticoid at equipotent dose)
Known abnormal value of left ventricular ejection fraction (LVEF <low limit of normal (LLN)), unless documented confirmation of recovery (LVEF >LLN) in the previous month
Females who are pregnant (negative serum or urine pregnancy test required for all females of child-bearing potential at screening) or breast feeding
QT interval corrected using Fridericia's formula (QTcF) >450 msec for males or >470 msec for females
Uncorrected hypokalaemia, hypocalcaemia (adjusted) and/or hypomagnesemia at screening
Troponin test performed at local laboratory >1.5 x ULN; or
Need for an unreplaceable drug that prolongs QT and it is clearly associated with a known risk for torsades de pointes (TdP); in case of being already on treatment with these aforementioned drugs, a minimum of 4 half-lives of the drug is required before replacement (if feasible)
Hypersensitivity to the active ingredient or any of the excipients (mannitol
macrogolglycerol hydroxystearate, and ethanol) or patients for whom
dexamethasone, antihistamine H1/H2 or antiserotoninergic agents are
contraindicated
Females and males with partners of child-bearing potential (females who are not surgically sterile or postmenopausal defined as amenorrhea for >12 months) who are not using at least 1 protocol specified method of contraception
Any other clinically significant medical condition (including major surgery within the last 3 weeks before screening) or laboratory abnormality that, in the opinion of the investigator, would jeopardise the safety of the patient or potentially impact on patient compliance or the safety/efficacy observations in the study
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