Efficacy of Thymosin Alpha 1 on Improving Monocyte Function for Sepsis

Study Overview
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Brief Summary
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The purpose of this study is to determine whether thymosin alpha 1 is effective on improving monocyte function and has the desired pharmacologic activity for sepsis

Detailed Description
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Part 1: To observe the function of thymosin alpha 1 in sepsis patients via improving phagocytosis, bacteria eradication and antigen-presenting on monocyte Part 2: Pharmacokinetics of thymosin alpha 1 for sepsis

Official Title
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Efficacy of Thymosin Alpha 1 on Improving Monocyte Function for Sepsis

Conditions
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Sepsis

Intervention / Treatment
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* Drug: thymosin alpha 1
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent from the patients or their next of kin for patients unable to consent Age ≥18 yrs Presence of sepsis/ septic shock according to sepsis 3.0 Exclusion Criteria: Pregnant or lactation period. Age <18 yrs Receiving immunosuppressive therapy such as cyclosporine, azathioprine or cancer chemotherapy within one month. History of bone marrow, lung, liver, kidney, pancreas or small bowel transplantation; Acute pancreatitis with no established source of infection. Not expected to survive 28 days because of end-stage diseases. Participation in another clinical trial.

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: thymosin alpha 1<br>Subcutaneous injections of 1.6 mg thymosin alpha 1 twice per day for seven days, the lyophilized powder is to be reconstituted with 1 ml of the provided diluent. | Drug: thymosin alpha 1<br>* Subcutaneous injections of 1.6 mg thymosin alpha 1 twice per day for seven days, prior to administration, the lyophilized powder is to be reconstituted with 1 ml of the provided diluent.<br>* Other names: thymalfasin;|
| Placebo Comparator: Placebo<br>Subcutaneous injections of placebo (saline) twice per day for seven days | Other: Placebo<br>* Subcutaneous injections of placebo (saline) twice per day for seven days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ta 1 improving immune function of monocyte for sepsis, used by flow cytometric to measure phagocytosis(CD11b, CD64), antigen presenting(HLA-DR, CD86 and PD-L1), and apoptosis(active caspase 3) on monocyte, | Phagocytosis was measured by expression of monocyte surface antigen CD64 and CD11b, as well as pHrodo™ BioParticles® Phagocytosis Kits to assessing phagocytic activity on monocyte; antigen presenting was measured by HLA-DR, costimulatory molecule CD86 and inhibitory molecule PD-L1 on monocyte; apoptosis was measured by active caspase 3 on monocyte | 28days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relationship between concentration of Ta 1 and prognosis of sepsis patients, measured by concentration of Ta 1, 28-day all-cause mortality, 28-day clearance rate of pathogenic microorganism, ICU stays and hospital stays | Concentration of Ta 1 was measured on day 0, 3 and 7 after injection drug or placebo | 28 days | 
| Maximum observed serum concentration (Cmax) of Ta 1 |  | 7 days | 
| Area under the serum concentration-time curve from time zero to time of last quantifiable concentration (AUC(0-T)) of Ta 1 |  | 7 days | 
| Terminal serum half-life (T-HALF) of Ta 1 |  | 7 days | 
| Time of maximum observed serum concentration (Tmax) of Ta 1 |  | 7 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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thymosin alpha 1; sepsis; monocyte; pharmacokinetics