Prevention of Severe SARS-CoV-2 Infection in Hospitalized Patients With COVID-19

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate if adding rhC1-INH to standard of care (SOC) in patients admitted for stage II COVID-19 infection may reduce the risk of disease progression, i.e. ALI requiring mechanical ventilation, or increase the chance of a faster clinical improvement compared to SOC alone.

Detailed Description
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Patients fulfilling all eligibility criteria will be randomized in a 2:1 ratio in an open-label controlled design to treatment with rhC1-INH in addition to SOC or SOC only starting on day 0. The first rhC1-INH treatment will be administered on the same day and continued for a total of 4 days.

Official Title
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Recombinant Human C1 Esterase Inhibitor (Ruconest®) in the Prevention of Severe SARS-CoV-2 Infection in Hospitalized Patients With COVID-19: a Randomized, Parallel-group, Open-label, Multi-center Pilot Trial in the United States (PROTECT-COVID-19-US)

Conditions
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Confirmed Coronavirus Disease

Intervention / Treatment
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* Drug: Ruconest


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-85 years, Admitted to the hospital because of confirmed positive SARS-CoV-2 (COVID-19 infection). Evidence of pulmonary involvement on CT scan or X-Ray of the chest, Symptom onset within the previous 10 days AND at least one additional risk factor for progression to mechanical ventilation: 1) arterial hypertension, 2) >50 years, 3) obesity (BMI>30.0 kg/m2), 4) history of cardiovascular disease, 5) chronic pulmonary disease, 7) chronic renal disease, 6) C-reactive protein of >35mg/L, 7) oxygen saturation at rest in ambient air of <94% Exclusion Criteria: Contraindications to the class of drugs under study (C1 esterase inhibitor); History or suspicion of allergy to rabbits; Women who are of childbearing potential and not using methods of contraception during the entire study period; Pregnant or breastfeeding females or has a positive serum β-human chorionic gonadotropin (hCG) pregnancy test at screening; Chronic liver disease (any Child-Pugh score B or C); Currently admitted to an ICU or expected admission within the next 24 hours; and Currently receiving invasive or non-invasive ventilation

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ruconest<br>Patients receive (150 U/ml) of Ruconest at a 50 U/kg dose (max dose of 4200 U) as a slow intravenous injection via a peripheral every 12 hours; for 4 days. A total of 8 doses will be administered. | Drug: Ruconest<br>* Patients will be randomized to Ruconest or Standard of Care<br>* Other names: SOC;|
| Other: Standard of Care<br>SOC | Drug: Ruconest<br>* Patients will be randomized to Ruconest or Standard of Care<br>* Other names: SOC;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Severity on the 7-Point WHO Ordinal Scale | The primary endpoint will be the disease severity on the 7-point WHO Ordinal Scale on day 7. This endpoint has been suggested by WHO for clinical trials in patients with COVID-19 | Assessed on each day after enrollment (worst status) with the use of the WHO Ordinal Scale and the score on day 7 will be analyzed stratified by its baseline value | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical improvement | at least 2 points Ordinal Scale for Clinical Improvement, clinical severity will be assessed. | Daily until day 14 | 
| Invasive or non-invasive ventilation | Admission to ICU with invasive or non-invasive ventilation or death will be assessed. | Daily until day 14. | 
| Acute Lung Injury | Patients with ALI within 14 days after enrollment, PaO2/FiO2 will be determined daily. This is only relevant for patients with arterial blood gas sampling performed in the ICU or rarely in the medical unit. | Daily until day 14. |