Annexin A5 in Patients With Severe COVID-19 Disease

Phase 2

Completed

• Conditions: Coronavirus Infection; Sepsis
• Interventions: Drug: Placebo; Drug: recombinant human annexin A5

• Registration Number: NCT04748757
• Lead Sponsor: Lawson Health Research Institute

Brief Summary

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-02-02
• Study First Submitted QC: 2021-02-09
• Study First Posted: 2021-02-10
• Study Start: 2021-04-20
• Primary Completion: 2022-04-03
• Study Completion: 2022-12-01
• Status Verified: 2023-03
• Last Update Submitted: 2023-03-07
• Last Update Posted: 2023-03-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

1. Age ≥ 19 years
2. Positive test for SARS-CoV-2 virus (anytime during current illness episode)
3. Admitted to intensive care for organ failure support (at least one of vasopressor, non-invasive or invasive ventilation)

Exclusion Criteria

1. Known allergy to any of the ingredients or components of the investigational product
2. Known pregnancy
3. Moribund and not expected to survive beyond 24 hours
4. 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)
5. Acute or chronic renal failure (dialysis dependent)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Normal saline, 50 ml infusion over 30 minutes every 12 hours for 7 days
Low dose	recombinant human annexin A5	50 microg/kg SY-005 in 50 ml saline infused over 30 minutes every 12 hours for 7 days
High dose	recombinant human annexin A5	100 microg/kg SY-005 in 50 ml saline infused over 30 minutes every 12 hours for 7 days

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

London Health Sciences Centre; 🇨🇦 London, Ontario, Canada