SY-005 （Recombinant Human Annexin A5）in Patients With Sepsis

Study Overview
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Brief Summary
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This Phase IIa Randomized, Double-blind, Parallel Group, Placebo-controlled, multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics and Efficacy of Multiple Intravenous Injection of SY-005（recombinant human annexin A5） in Sepsis Subjects. 96 patients will be entered into the study and randomised in a 1:1:1:1 ratio to receive SY-005 2.5mg or SY-005 5mg or SY-005 10mg or placebo.

Official Title
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A Phase IIa Randomized, Double-blind, Parallel Group, Placebo-controlled, Multicenter Study to Evaluate Safety, Tolerability, Pharmacokinetics and Efficacy of Multiple Intravenous Injection of SY-005 in Sepsis Subjects

Conditions
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Sepsis

Intervention / Treatment
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* Drug: SY-005
* Drug: SY-005
* Drug: SY-005
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Patients are diagnosed with sepsis and receive study treatment within 48 hours Sepsis-related Organ Failure Assessment（SOFA）score range from 2 to 13 The informed consent form signed by the patient or the patient's legally acceptable representative Key Exclusion Criteria: Pregnant or breastfeeding women ; Women of childbearing potential (WOCBP) could not take effective method of contraception Moribund, and death is considered imminent within 24 hours or patient expected survival time is less than 6 months due to the underlying disease Absolute neutrophil count (ANC) <0.5 x 10^9/L New York Heart Association (NYHA) classification IV Patient with end-stage lung disease eGFR <60ml/min Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >3.0 times the upper limit of normal (ULN) Immunosuppressed patients with following situations: Human immunodeficiency virus (HIV) infection Patients undergoing active radiation or chemotherapy treatment within the past 3 months Any organ or bone marrow transplant and related immunosuppressive therapy High dose steroids (eg, > 0.5 mg/kg prednisone or a steroid with equivalent activity, daily for a month) within 3 months before provision of written informed consent for the study Patients with high bleeding risk: Recent surgery <72 hours, or a planned surgical procedure in the next 24h Severe thrombocytopenia (< 30 x 10^9/L, before platelet transfusion) Recent trauma <72 hours History of gastrointestinal bleeding or intracranial hemorrhage in the past 6 weeks. Stroke or head injury in the past 3 months On-going therapeutic anticoagulants that could not be interrupted (except prophylactic heparin treatment that can be continued） Any history of Chronic liver disease with a Child score B or C Any condition at risk of bleeding, as appreciated by the physician in charge of the patient Severe anemia (hemoglobin <5.9 g/dL)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2.5mg SY-005<br> | Drug: SY-005<br>* 2.5mg of SY-005 for each dose，doses to be given every 12 hours over a period of 5 days<br>|
| Experimental: 5mg SY-005<br> | Drug: SY-005<br>* 5mg of SY-005 for each dose，doses to be given every 12 hours over a period of 5 days<br>|
| Experimental: 10mg SY-005<br> | Drug: SY-005<br>* 10mg of SY-005 for each dose，doses to be given every 12 hours over a period of 5 days<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability Parameters of SY-005 | Number of patients with treatment-emergent adverse events over 28 days | From Day 0 to Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score at Day 1, Day3, Day5, Day7 |  | Baseline, Day 1, Day3, Day5, Day7 | 
| Vasopressin Free Days From Day 0 to Day 28 |  | From Day 0 to Day 28 | 
| Assessment of ICU-Free Days From Day 0 to Day 28 |  | From Day 0 to Day 28 | 
| Ventilator-Free Days From Day 0 to Day 28 |  | From Day 0 to Day 28 | 
| 7-Day and 28-Day Mortality |  | Over 7/28 Days Following First Dose | 
| Change From Baseline in IL-1β at Day 3，Day5 |  | Baseline, Day 3，Day5 | 
| Change From Baseline in IL-6 at Day 3，Day5 |  | Baseline, Day 3，Day5 | 
| Change From Baseline in Procalcitonin at Day 3，Day5 |  | Baseline, Day 3，Day5 | 
| Change From Baseline in Prothrombin Time at Day 3，Day5 |  | Baseline, Day 3，Day5 | 
| Change From Baseline in Thrombin Time at Day 3，Day5 |  | Baseline, Day 3，Day5 | 
| Change From Baseline in Activated Partial Thromboplastin Time at Day 3，Day5 |  | Baseline, Day 3，Day5 | 
| Change From Baseline in Fibrinogen at Day 3，Day5 |  | Baseline, Day 3，Day5 | 
| Change From Baseline in Chemokine(C-C motif) Ligand 2 at Day 3，Day5 |  | Baseline, Day 3，Day5 | 
| Change From Baseline in Anti-drug Antibodies at Day7，Day14，Day28 |  | Baseline, Day7，Day14，Day28 |