Annexin A5 in Patients With Severe COVID-19 Disease

Study Overview
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Brief Summary
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Randomized, double-blind, placebo-controlled trial comparing 2 doses of SY-005 (recombinant human Annexin A5) to placebo in patients with severe coronavirus 2019 disease in a single hospital centre with 2 intensive care units

Official Title
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Annexin A5 in Patients With Severe COVID-19 Disease: A Single Centre, Randomized, Double-blind, Placebo-controlled Pilot Trial

Conditions
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Coronavirus Infection, Sepsis

Intervention / Treatment
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* Drug: recombinant human annexin A5
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 19 years Positive test for SARS-CoV-2 virus (anytime during current illness episode) Admitted to intensive care for organ failure support (at least one of vasopressor, non-invasive or invasive ventilation) Exclusion Criteria: Known allergy to any of the ingredients or components of the investigational product Known pregnancy Moribund and not expected to survive beyond 24 hours Known or suspected risk for serious bleeding complications (note that Disseminated Intravascular Coagulopathy (DIC) is an expected finding in patient with sepsis and COVID-19 disease and is not an exclusion criterion on its own) Acute or chronic renal failure (dialysis dependent)

Ages Eligible for Study
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Minimum Age: 19 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Normal saline, 50 ml infusion over 30 minutes every 12 hours for 7 days | Drug: Placebo<br>* Normal saline 50 ml<br>|
| Experimental: Low dose<br>50 microg/kg SY-005 in 50 ml saline infused over 30 minutes every 12 hours for 7 days | Drug: recombinant human annexin A5<br>* recombinant human annexin A5, manufactured as SY-005<br>* Other names: SY-005;|
| Experimental: High dose<br>100 microg/kg SY-005 in 50 ml saline infused over 30 minutes every 12 hours for 7 days | Drug: recombinant human annexin A5<br>* recombinant human annexin A5, manufactured as SY-005<br>* Other names: SY-005;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Enrollment | Participants enrolled per site per month with success defined as enrollment >= 50% of screened eligible patients | 12 months | 
| Protocol adherence | Delivery of investigational product within 1 hour of scheduled dose; success defined as >= 90% | 7 days | 
| Data completeness | Case Report Forms completed with <10% missing data after verification and monitoring | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Organ failure | Sequential Organ Failure Assessment (SOFA) at 30 days; range 0 (normal) to 24 | 30 days | 
| Organ function at end of treatment measured with SOFA | SOFA at end of treatment (EOT) | 7 days | 
| Organ function at end of treatment measured with Multiple Organ Dysfunction Score (MODS) | MODS at end of treatment (EOT); range 0 (normal) to 24 | 7 days | 
| Individual organ function scores at EOT measured with SOFA | SOFA for individual organ systems | 30 days | 
| Individual organ function scores at 30 days measured with SOFA | SOFA for individual organ systems | 30 days | 
| Individual organ function scores at EOT measured with MODS | MODS for individual organ systems | 30 days | 
| Individual organ function scores at 30 days measured with MODS | MODS for individual organ systems | 30 days | 
| Plasma annexin A5 levels daily days 1-8 (treatment period) and on day 14 | Annexin A5 will be measured daily during treatment and on day 14 | 14 days | 
| Mortality at 60 days | All cause mortality | 60 days | 
| Hospital mortality | Hospital mortality censored at 60 days | 60 days | 
| Ventilator-free days | Days alive and off ventilator at 30 days | 30 days | 
| ICU-free days | Days alive and not in ICU at 30 days | 30 days | 
| Number of participants with persistent organ dysfunction | MODS score greater or equal to 2 in any organ system at day 30 | 30 days | 
| Number of serious adverse events (SAE) | SAE | 60 days | 
| Maximum plasma concentration (Cmax) of annexin A5 (SY-005) | Pharmacokinetic profile on day 1 | 1 day | 
| Elimination half-life of annexin A5 (SY-005) | Pharmacokinetic profile on day 1 | 1 day | 
| Number of participants with anti-annexin A5 antibodies | Anti-annexin A5 antibodies | 21 days |