A Study Evaluating the Efficacy and Safety of CKD-314 (Nafabelltan) in Hospitalized Adult Patients Diagnosed With COVID-19 Pneumonia

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the efficacy of CKD-314 (Nafabelltan) compared to standard of care (SOC), with respect to clinical status assessed by a 7-point ordinal scale in hospitalized adult patients diagnosed with COVID-19 pneumonia

Official Title
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An Open-label, Randomized, Multicenter, Controlled Clinical Trial to Evaluate the Efficacy and Safety of CKD-314 (Nafabelltan) in Hospitalized Adult Patients Diagnosed With COVID-19 Pneumonia

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Nafamostat Mesilate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women Aged ≥18 years Hospitalized subjects who have confirmed COVID-19 infection and have evidence of pneumonia: Subjects who are eligible for diagnosis/evaluation to chest X-ray or chest CT Women of childbearing potential (including women in post menopause for less than 2 years) must use a medically acceptable forms of birth control and agree to continue its use during the study Subjects (or legally authorized representative) should be able to understand and agree to comply with the clinical trial and to provide a written consent document prior to initiation of any study procedure Exclusion Criteria: Subjects who have a record of HIV or AIDS Subject has a serious chronic disease Active bleeding or ongoing clinical condition deemed at high risk of bleeding contraindicating anticoagulant treatment Pregnant or lactating females Subjects with liver cirrhosis whose Child-Pugh score is B or C Subjects who have liver disease abnormalities with ALT or AST > 5 times ULN Estimated glomerular filtration rate (eGFR) < 30 ml/min (including patients receiving hemodialysis or hemofiltration) QTcB or QTcF >500ms Subjects who have clinically significant ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation) in medical history Subjects with rapidly deteriorating clinical condition or low likelihood to complete the study according to the investigator's opinion Subjects who are not appropriate for the study, as the investigator's opinion Subjects who have hypersensitivity to the investigational drug Subjects participated in any other clinical trial (including drugs for the treatment of COVID-19) 3 months prior to screening

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 |
| --- | --- |
| No Intervention: Standard of Care<br>Standard of Care Treatment for COVID-19 Infection | |
| Experimental: Nafamostat + Standard of Care<br>Nafamostat mesylate on top of standard of care | Drug: Nafamostat Mesilate<br>* Administered intravenously as a continuous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to clinical improvement | Time to clinical improvement (TTCI) was defined as time (days) from randomization to a decline of 2 categories on the seven-category ordinal scale of clinical status or live discharge from the hospital, whichever came first | up to 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to recovery | Day of recovery is defined as the first day on which the subject satisfies one of the following: 1) Not hospitalized with resumption of normal activities; 2) Not hospitalized, but unable to resume normal activities; 3) Hospitalization, not requiring supplemental oxygen- no longer required ongoing medical care | up to 28 days | 
| Proportion of patients with clinical improvement as defined by live discharge from hospital or a decline of 2 categories on the seven-category ordinal scale of clinical status |  | Day 4, 7, 11, 14 and 28 | 
| Proportion of patients with recovery as defined as the subject satisfies one of the following | 1) Not hospitalized with resumption of normal activities; 2) Not hospitalized, but unable to resume normal activities; 3) Hospitalization, not requiring supplemental oxygen- no longer required ongoing medical care | Day 4, 7, 11, 14 and 28 | 
| Change of clinical status assessed by 7-category ordinal scale |  | Day 4, 7, 11, 14 and 28 | 
| Change in National Early Warning Score (NEWS) |  | Day 4, 7, 11, 14 and 28 | 
| Time to National Early Warning Score (NEWS) of ≤ 2 which is maintained for 24 hours |  | up to 28 days | 
| Changes on CT scan/X-ray | Measured as proportion of patients with improved, not changed or worsened CT scan/X-ray | Day 5, 11, 14 and 28 | 
| Change from baseline of CRP |  | Day 4, 7, 11, 14 and 28 | 
| Time to normalize the CRP | Decrease to the level of <10 mg/l | up to 28 days | 
| Duration of hospitalization |  | up to 28 days | 
| Duration of non-invasive ventilation or high flow oxygen use |  | up to 28 days | 
| Incidence of non-invasive ventilation or high flow oxygen use | Proportion of patients of non-invasive ventilation or high flow oxygen use | up to 28 days | 
| Duration of supplement oxygen use |  | up to 28 days | 
| Incidence of supplement oxygen use | Proportion of patients of supplement oxygen use | up to 28 days | 
| Duration of invasive ventilation or extracorporeal membrane oxygenation (ECMO) use |  | up to 28 days | 
| Incidence of invasive ventilation or extracorporeal membrane oxygenation (ECMO) use | Proportion of patients of invasive ventilation or extracorporeal membrane oxygenation (ECMO) use | up to 28 days | 
| 28-Day mortality |  | up to 28 days |