A Study to Evaluate the Safety and Effect of STC314 Injection Continuous Infusion in Subjects With Acute Respiratory Distress Syndrome
Study Details
Study Description
Brief Summary
This study is a Randomized, Double-blinded, Placebo-controlled Phase Ib Study to Evaluate the Safety, Tolerability and Pharmacokinetics of STC314 Injection Administered as Continuous Intravenous Infusion in Chinese Patients with ARDS (Acute Respiratory Distress Syndrome).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Cohort 1 Drug: STC314/Placebo injection Continuous infusion at rate 58.3mg/hr up to 3 days (72 hours) N=8(Randomization-STC314/Placebo injection=3:1) |
Drug: STC314 injection or Placebo(rate=58.3 mg/hr)
To receive continuous infusion of STC314/Placebo injection at rate 58.3mg/hr up to 3 days (72hours). Also to receive appropriate standard of care.
|
| Experimental: Cohort 2 Drug: STC314/Placebo injection Continuous infusion at rate 87.5mg/hr up to 3 days (72 hours) N=8(Randomization-STC314/Placebo injection=3:1) |
Drug: STC314 injection or Placebo(rate=87.5 mg/hr)
To receive continuous infusion of STC314/Placebo injection at rate 87.5mg/hr up to 3 days (72hours). Also to receive appropriate standard of care.
|
Outcome Measures
Primary Outcome Measures
- To evaluate the safety of STC314 injection in patients with ARDS. [Within 28 days after the start of treatment]
The incidence of adverse event (AE) and serious adverse event (SAE);
- To evaluate the safety of STC314 injection in patients with ARDS. [Within 28 days after the start of treatment]
Rates of Treatment Discontinuation Due to Adverse Events;
- To evaluate the pharmacokinetic of STC314 injection in patients with ARDS. [Through 0 to144 hours after the start of treatment]
maximum concentration (Cmax)
- To evaluate the pharmacokinetic of STC314 injection in patients with ARDS. [Through 0 to144 hours after the start of treatment]
area under the plasma concentration-time curve (AUC0-t, AUC0-inf)
- To evaluate the pharmacokinetic of STC314 injection in patients with ARDS. [Through 0 to144 hours after the start of treatment]
time to peak (Tmax)
- To evaluate the pharmacokinetic of STC314 injection in patients with ARDS. [Through 0 to144 hours after the start of treatment]
elimination half Decay (t1/2)
- To evaluate the pharmacokinetic of STC314 injection in patients with ARDS. [Through 0 to144 hours after the start of treatment]
elimination rate constant(Kel)
- To evaluate the pharmacokinetic of STC314 injection in patients with ARDS. [Through 0 to144 hours after the start of treatment]
clearance (CL)
Secondary Outcome Measures
- To evaluate the efficacy of STC314 injection in patients with ARDS. [Within 28 days after the start of treatment]
Changes of the value of blood lactate from baseline after dosing
- To evaluate the efficacy of STC314 injection in patients with ARDS. [Within 28 days after the start of treatment]
Change of Oxygenation Index (PaO2/FiO2) from baseline after dosing
- To evaluate the efficacy of STC314 injection in patients with ARDS. [Within 28 days after the start of treatment]
Change of Murray Lung Injury Score from baseline.(range 0-4, higher score means more severe lung injury)
- To evaluate the efficacy of STC314 injection in patients with ARDS. [Within 28 days after the start of treatment]
Change of the value of serum creatinine from baseline after dosing
- To evaluate the efficacy of STC314 injection in patients with ARDS. [Within 28 days after the start of treatment]
Change of the value of bilirubin from baseline after dosing
- To evaluate the efficacy of STC314 injection in patients with ARDS. [Within 28 days after the start of treatment]
Change of the value of Alanine Transaminase(ALT) from baseline after dosing
- To evaluate the efficacy of STC314 injection in patients with ARDS. [Within 28 days after the start of treatment]
Change of Sequential Organ Failure Assessment score from baseline after dosing.(range 0-4, higher score means a worse prognosis)
- To evaluate the efficacy of STC314 injection in patients with ARDS. [Within 28 days after the start of treatment]
all-cause mortality within 28 days
- To evaluate the efficacy of STC314 injection in patients with ARDS. [Within 28 days after the start of treatment]
Ventilator-free survival time within 28 days
- To evaluate the efficacy of STC314 injection in patients with ARDS. [Within 28 days after the start of treatment]
Hospitalization time within 28 days
- To evaluate the efficacy of STC314 injection in patients with ARDS. [Within 28 days after the start of treatment]
length of ICU stay within 28 days
Other Outcome Measures
- As an exploratory objective, the change in biomarkers from baseline following STC314 injection treatment in subjects with Acute Respiratory Distress Syndrome will be evaluated. [Through 0 to144 hours after the start of treatment]
Change of the level of Histone in plasma after dosing
- As an exploratory objective, the change in biomarkers from baseline following STC314 injection treatment in subjects with Acute Respiratory Distress Syndrome will be evaluated. [Through 0 to144 hours after the start of treatment]
Change of the level of Neutrophil extracellular traps(NETs)-related variables in plasma after dosing [myelinated Oxidase (MPO), citrullinated histone H3 (CitH3), circular free DNA (cfDNA)]
- As an exploratory objective, the change in biomarkers from baseline following STC314 injection treatment in subjects with Acute Respiratory Distress Syndrome will be evaluated. [Through 0 to144 hours after the start of treatment]
Change of the level of inflammatory factor interleukin-6 (IL-6) after dosing
Eligibility Criteria
Criteria
Inclusion Criteria:
-
18 ≤ age ≤ 70 years, male or female;
-
Voluntarily participate in the study and sign the informed consent form;
-
Diagnosis of ARDS for no more than 48 hours (starting at the time of diagnosis recorded in the medical record)；
-
The following 2012 Berlin definition criteria for mild to moderate ARDS were met:
-
From known clinical impairment and new or worsening of respiratory symptoms to fulfillment of diagnostic criteria is less than 7 days(inclusive).
-
Chest imaging suggests bilateral infiltrates. The effusion, lobar/atelectasis, or nodules cannot completely explain the phenomenon.
-
Respiratory failure cannot be completely explained by heart failure or fluid overload;
-
When PEEP or CPAP ≥5 cm H2O, 100 mmHg≤PaO2/FiO2≤300 mmHg;
-
Male subjects agree to use an effective contraceptive method from the start of the study until 7 days after the end of treatment; Female subjects of childbearing age agree to use an effective contraceptive method from the start of the study until 3 months after the end of treatment.
Exclusion Criteria:
-
Positive serum pregnancy test before dosing for women of childbearing potential, pregnant women, or lactating women;
-
Terminal phase of chronic disease with an expected survival of no more than 6 months;
-
Combined with one of the following chronic organ damage or immunosuppressive diseases:
-
Heart: New York Heart Association functional class IV;
-
Lung: severe lung disease, including pulmonary hypertension, oxygen therapy or ventilator dependence for more than one month cumulatively within the first six months of screening, end-stage lung disease, or severe exercise limitation caused by chest wall malformations;
-
Kidney: ongoing long-term dialysis treatment;
-
Liver: biopsy confirmed cirrhosis and portal hypertension, or previous upper gastrointestinal bleeding caused by portal hypertension; Liver failure, hepatic encephalopathy, or hepatic coma;
-
Immunosuppression: with lymphoma, leukemia or acquired immunodeficiency; Received anti-tumor chemotherapy in the last 3 months, or ongoing immunosuppressive therapy due to organ transplantation, immune diseases, etc.; Has undergone allogeneic bone marrow transplantation or hematopoietic stem cell transplantation; Steroid hormone therapy in the last 3 months (equivalent to > 0.5 mg/kg/day prednisone continued 1 month);
-
History of one of the following within 4 weeks prior to screening:
-
Acute pulmonary embolism;
-
Cardiac arrest;
-
Acute myocardial infarction;
-
eGFR < 60 mL/min/BSA (calculated using CG formula);
-
ALT > 5 x ULN, or total bilirubin > 2 x ULN;
-
Severe anemia (hemoglobin < 7.0 g/dL);
-
Absolute neutrophil count < 1500/μL;
-
Platelet count < 50,000/μL;
-
aPTT > 1.5 × ULN;
-
Active bleeding that cannot be effectively controlled;
-
The subject required therapeutic doses of heparin or was taking anticoagulants;
-
ARDS caused by direct lung injury due to physical or chemical causes;
-
Severe or greater burns: the overall surface area of burns exceeds 30% or the III degree burn area exceeds 10%; or the total area is less than 30%, but the general condition is severe or has shock, combined injury, respiratory tract burn;
-
Allergic to the active ingredients or excipients of the study drug;
-
Subjects have participated in other clinical studies (other than those who have not received intervention) or are participating in other experimental treatments within 1 month prior to screening;
-
In the opinion of the investigator, the subject could not benefit from the study or was not suitable for participation in the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The Fourth Hospital of Hebei Medical University | Shijiazhuang | Hebei | China | |
| 2 | Wuhan Jinyintan Hospital | Wuhan | Hubei | China | |
| 3 | Wuhan Union Hospital | Wuhan | Hubei | China | |
| 4 | Xiangya Hospital Central South University | Changsha | Hunan | China | |
| 5 | Zhongda Hospital Southeast University | Nanjing | Jiangsu | China |
Sponsors and Collaborators
- Grand Medical Pty Ltd.
- Grand Pharmaceutical (China) Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GPHIP-0103