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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Sepsis
• Intervention / Treatment: Drug: Placebo; Drug: SY-005; Drug: SY-005; Drug: SY-005

• Study Type: Interventional
• Enrollment (Anticipated): 96
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yi Yang; Phone Number: +86 025-83272015; Email: yiyiyang2004@163.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Recruiting
      • Zhongda Hospital,Affiliated to Southeast University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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	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

Collaborators and Investigators

• Sponsor: Suzhou Yabao Pharmaceutical R&D Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): January 2, 2022
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): July 1, 2023

Study Registration Dates

• First Submitted: May 11, 2021
• First Submitted That Met QC Criteria: May 20, 2021
• First Posted (Actual): May 24, 2021

Study Record Updates

• Last Update Posted (Actual): March 14, 2022
• Last Update Submitted That Met QC Criteria: February 27, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Sepsis; Toxemia
• Other Study ID Numbers: SY005002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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