Annexin A5 in Patients With Severe COVID-19 Disease (AX-COVID)

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

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

Study Overview

• Status: Recruiting
• Conditions: Coronavirus Infection; Sepsis
• Intervention / Treatment: Drug: Placebo; Drug: recombinant human annexin A5

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Eileen Campbell; Phone Number: 5196858090; Email: eileen.campbell@lhsc.on.ca

Study Locations

• Canada
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Recruiting
      • London Health Sciences Centre
      • Contact: Eileen Campbell; Phone Number: 55664 519-685-8500; Email: Eileen.Campbell@lhsc.on.ca
      • Contact: Claudio Martin, MD, MSc; Phone Number: 58090 519-685-8500; Email: cmartin1@uwo.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Lawson Health Research Institute
• Collaborators: London Health Sciences Foundation; Ontario Ministry of Colleges and Universities
• Investigators: Principal Investigator: Claudio Martin, MD, MSc, Lawson Health Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 20, 2021
• Primary Completion (Anticipated): March 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: February 2, 2021
• First Submitted That Met QC Criteria: February 9, 2021
• First Posted (Actual): February 10, 2021

Study Record Updates

• Last Update Posted (Actual): April 27, 2021
• Last Update Submitted That Met QC Criteria: April 23, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Coronavirus Infections; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Annexin A5
• Other Study ID Numbers: REDA-10122

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Information and data sharing will be considered on individual basis at conclusion of the study.
• IPD Sharing Time Frame: To be evaluated on individual basis
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No