Clinical trial NCT04898322: SY-005 （Recombinant Human Annexin A5）in Patients With Sepsis
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Sepsis
Lead sponsor: Suzhou Yabao Pharmaceutical R&D Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2021-05-24
Enrollment: 96
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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:

  1. Human immunodeficiency virus (HIV) infection
  2. Patients undergoing active radiation or chemotherapy treatment within the past 3 months
  3. Any organ or bone marrow transplant and related immunosuppressive therapy
  4. 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:

  1. Recent surgery \<72 hours, or a planned surgical procedure in the next 24h
  2. Severe thrombocytopenia (\< 30 x 10\^9/L, before platelet transfusion)
  3. Recent trauma \<72 hours
  4. History of gastrointestinal bleeding or intracranial hemorrhage in the past 6 weeks.
  5. Stroke or head injury in the past 3 months
  6. On-going therapeutic anticoagulants that could not be interrupted (except prophylactic heparin treatment that can be continued）
  7. Any history of Chronic liver disease with a Child score B or C
  8. Any condition at risk of bleeding, as appreciated by the physician in charge of the patient
* Severe anemia (hemoglobin \<5.9 g/dL)

Primary outcomes:
measure: Safety and Tolerability Parameters of SY-005
timeFrame: From Day 0 to Day 28
Secondary outcomes:
measure: Change From Baseline in Sequential Organ Failure Assessment (SOFA) Score at Day 1, Day3, Day5, Day7
timeFrame: Baseline, Day 1, Day3, Day5, Day7
measure: Vasopressin Free Days From Day 0 to Day 28
timeFrame: From Day 0 to Day 28
measure: Assessment of ICU-Free Days From Day 0 to Day 28
timeFrame: From Day 0 to Day 28
measure: Ventilator-Free Days From Day 0 to Day 28
timeFrame: From Day 0 to Day 28
measure: 7-Day and 28-Day Mortality
timeFrame: Over 7/28 Days Following First Dose
measure: Change From Baseline in IL-1β at Day 3，Day5
timeFrame: Baseline, Day 3，Day5
measure: Change From Baseline in IL-6 at Day 3，Day5
timeFrame: Baseline, Day 3，Day5
measure: Change From Baseline in Procalcitonin at Day 3，Day5
timeFrame: Baseline, Day 3，Day5
measure: Change From Baseline in Prothrombin Time at Day 3，Day5
timeFrame: Baseline, Day 3，Day5
measure: Change From Baseline in Thrombin Time at Day 3，Day5
timeFrame: Baseline, Day 3，Day5
measure: Change From Baseline in Activated Partial Thromboplastin Time at Day 3，Day5
timeFrame: Baseline, Day 3，Day5
measure: Change From Baseline in Fibrinogen at Day 3，Day5
timeFrame: Baseline, Day 3，Day5
measure: Change From Baseline in Chemokine(C-C motif) Ligand 2 at Day 3，Day5
timeFrame: Baseline, Day 3，Day5
measure: Change From Baseline in Anti-drug Antibodies at Day7，Day14，Day28
timeFrame: Baseline, Day7，Day14，Day28
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Zhongda Hospital，Affiliated to Southeast University
state: Jiangsu
Study officials:
References: