Investigating the Efficacy and Safety ICATIBANT For The Treatment of Patients With SARS-CoV-2 (COVID-19) Infection

Study Overview
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Brief Summary
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To study the efficacy and safety of icatibant in adult patients admitted to hospitalization units for pneumonia caused by COVID-19, without mechanical ventilation, 10±1 days after starting treatment or discharge from hospital if this occurs before 10 days.

Official Title
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Randomized, Open, Multicenter Phase II Clinical Trial, Proof of Concept, to Evaluate Efficacy and Safety of Icatibant in Hospitalized Patients With SARS-COV-2 (COVID-19) Without Assisted Ventilation Compared With Standard Care

Conditions
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COVID-19 Pneumonia

Intervention / Treatment
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* Drug: Firazyr
* Other: SoC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult patients (18 years or older), both sexes Sars-CoV-2 infection confirmed by PCR less than 4 days before randomization hospitalized with a diagnosis of SARS-CoV-2 pneumonia radiographic evidence of pulmonary infiltrates grade 4 or 5 on the ordinal scale for the evaluation of the patient's clinical condition pO2/FiO2 <380 men and women of childbearing age who have heterosexual relations must be agreement to use the safe method(s) of contraception obtaining the informed consent of the patient or the legal representative. Exclusion Criteria: imminent death (life expectancy less than 72h) known hypersensitivity or known adverse reactions to the study drug, or its metabolites or excipients of the formulation invasive mechanical ventilation participation in any other clinical trial ALT or AST > 5 x ULN creatinine clearance <50 mL/min using the Cockcroft-Gault formula for participants '18 years old [Cockcroft 1976] patients with recent acute coronary syndrome (<1 month) patients with a history of stroke positive pregnancy test pregnant or lactating woman

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard of Care (SoC)<br> | Other: SoC<br>* The SoC could include respiratory support measures, fluid therapy, antipyretic treatment, postural measures, low-molecular-weight-heparins, corticosteroids, such as dexamethasone, remdesivir and other therapeutic options<br>|
| Experimental: SoC + Icatibant<br> | Drug: Firazyr<br>* Icatibant 10 MG/ML Prefilled Syringe<br>Other: SoC<br>* The SoC could include respiratory support measures, fluid therapy, antipyretic treatment, postural measures, low-molecular-weight-heparins, corticosteroids, such as dexamethasone, remdesivir and other therapeutic options<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of experimental treatment | Number of patients reaching grade 2 (inpatient, no longer requiring supplemental oxygen and no longer requiring care or grade 1 (hospital discharge) of the ordinal scale of the clinical state of the patient for 48 hours. | up to 10 days | 
| Safety of experimental treatment | Number of patients without an adverse reaction scoring 3, 4 or 5 according to the Criteria of Adverse Event Terminology (CTC-AE). | up to 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long-term efficacy | Number (percentage) of patients who reach grade 2 or grade 1 during the 10 days of to have initiated treatment. | up to 10 days | 
| Time to achive a clinical response | period time (days) between visit 1 (treatment start visit) and the day of gathering sustained 48-hour grade 2, grade 1 or grade 0 classification on the WHO 8-point ordinal scale for clinical status assessment The patient must be discharged from the hospital by the 28th day without a relapse or comorbidity related to COVID-19 | up to 40 days | 
| Time to achive an afebrile state | period time (days) to reach a 48-hour sustained afebrile state (i.e., body temperature ≤ 37.5ºC) without antipyretic medication. | up to 40 days | 
| time from symptom onset to treatment | period time (days) between the first COVID-19-related symptom and visit 1 (treatment start visit). | up to day 1 | 
| Responders | Number (percentage) of patients considered as responders based on National Early Warning Score 2 (NEWS 2) | up to 40 days | 
| COVID-19 related relapse | number (and percentage) of patients discharged who presents any COVID-19-related relapse or comorbidity | up to 40 days | 
| Patients with Adverse Events | number of patients with Any Adverse Events | up to 40 days | 
| Adverse Events | Number of Adverse Events | up to 40 days | 
| Serious Adverse Events | Number of Serious Adverse Events | up to 40 days | 
| Overall mortality | number of patients who died | up to 40 days | 
| COVID-19 related mortality | number of patients who died due to COVID-19 | up to 40 days | 
| Time until death | number of days from visit 1 until death | up to 40 days | 
| COVID-19-related complications | number of patients who had any COVID-19 related complications | up to 40 days | 
| Patients requiring intensive care | number of patients who require intensive care | up to 40 days | 
| patients requiring intensive care and invasive mechanical ventilation | number of patients who require intensive care and invasive mechanical ventilation | up to 40 days | 
| patients requiring oxygen supplementation | number of patients who require oxygen supplementation from hospital discharge up until visit 7 | up to 40 days | 
| Patients with nonsocomial infection | number (and percentage) of patients diagnosed with another nosocomial infection | up to 40 days | 
| Rehospitalizations | number (and percentage) of patients who requires hospital readmission within 28 (± 3) days from hospital discharge | up to 40 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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icatibant