Senicapoc in COVID-19 Patients With Severe Respiratory Insufficiency

Study Overview
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Brief Summary
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SARS-CoV-2, one of a family of human coronaviruses, was initially identified in December 2019 in Wuhan city. This new coronavirus causes a disease that has now been named COVID-19. The virus has subsequently spread throughout the world and was declared a pandemic by the World Health Organisation on 11th March 2020. As of April 1, 2020, there are 874.081 numbers of confirmed cases with 43.290 fatalities. There is no approved therapy for COVID-19 and the current standard of care is supportive treatment. Key markers implying a fatal outcome are acute respiratory distress syndrome (ARDS)-like disease with pronounced dyspnea, hypoxia and radiological changes in the lung. Senicapoc improves oxygenation and reduces fluid retention, inflammation, and bleeding in the lungs of mice with ARDS-like disease. In cells, there is an antiviral effect of senicapoc.

Detailed Description
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The investigators discovered that in an animal model with a knockout of a potassium channel with intermediate conductance (KCa3.1), the knockout protected against lung damage and accumulation of liquid in the lung. In subsequent studies, the investigators have developed a mouse model showing that genetic deletion of the KCa3.1 channels and senicapoc, a blocker of KCa3.1 channels, protects against the accumulation of liquid in the lung. Moreover, senicapoc treatment possesses anti-inflammatory effects illustrated as lower leukocyte accumulation inside the lungs after injury. Importantly, it also increases the FiO2/PaO2 ratio (ratio of inhaled to blood oxygen), hence preserving lung function in mice with an ARDS-like disease. In addition, there is evidence that senicapoc has antiviral properties. Aarhus University has patented senicapoc for use in the treatment of acute respiratory disease. In this case, respiratory disease is caused by an infection with a coronavirus. Senicapoc has been developed for the treatment of sickle cell disease and has been administered to 500 patients without observation of major treatment-related adverse effects.

Official Title
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Senicapoc in COVID-19 Patients With Severe Respiratory Insufficiency - A Randomized, Open-Label, Phase II Trial

Conditions
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ARDS, Human, COVID

Intervention / Treatment
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* Drug: Senicapoc


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: COVID-19 positive Age ≥18 years Respiratory insufficiency ICU admission Exclusion Criteria: Severe heart failure (ejection fraction < 30%) Severe renal insufficiency (eGFR < 30 mL/min/1.73m2) Severe hemodynamic instability (noradrenalin dose > 0.3 μg/kg/min) Prior enrollment in the trial Pregnancy Allergy to senicapoc Inability to take enteral medication More than 24 hours since ICU admission Limitations of care Anticipated death within 24 hours

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
Interventional Model Description: A Randomized, Open-Label, Phase II Trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Standard treatment<br>Standard intensive care | |
| Active Comparator: Senicapoc<br>Senicapoc | Drug: Senicapoc<br>* The intervention will consist of 50 mg enteral senicapoc administered as soon as possible after randomization and again after 24 hours<br>* Other names: ICA-17043;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PaO2/FiO2 ratio | The PaO2/FiO2 ratio will be calculated based on the arterial gas closest to the time-point of Day 3 after randomization | Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilator-free days | Ventilator-free days will be defined as the number of days (or proportion of days) within the first 28 days after randomization where the patient is alive and not on invasive mechanical ventilation | Day 28 | 
| Mortality | Assessment of mortality is considered a core outcome for trials within acute respiratory failure | Day 28 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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senicapoc, severe acute respiratory distress syndrome, SARS-COV2, corona virus infection