Phase Ib of Recombinant Human Albumin Injection

Study Overview
=================
Brief Summary
-----------------
A Randomized, Multicenter,Open-label, positive-controlled, Multi-dose Phase 1 Study to Evaluate the Safety, Tolerance,Efficacy, Pharmacokinetics and Immunogenicity of recombinant human albumin injection in Patients With Hepatic Cirrhosis

Detailed Description
-----------------
This study was to evaluate the safety, tolerability,efficacy, pharmacokinetics and immunogenicity of recombinant human albumin injection in Patients With Hepatic Cirrhosis. The study design consists of two phases: Screening and treatment phase(dose increasing stage).Following the Screening phase, all eligible subjects will be randomized to receive recombinant human albumin injection or HumanAlbumin, study medication in a 3:1 ratio.Dose increasing stage (including 3 dose groups with increasing dose, and each group was set with HumanAlbumin control).The initial dose was 10g. The highest dose group was set at 30g.

Official Title
-----------------
Phase Ib Study of Recombinant Human Albumin Injection for the Treatment of Ascites in Patients With Hepatic Cirrhosis

Conditions
-----------------
Ascites

Intervention / Treatment
-----------------
* Drug: Recombinant Human Albumin Injection
* Drug: HumanAlbumin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18-75 years of age; No less than 45 kg. Diagnosed with ascites due to cirrhosis. Exclusion Criteria: Allergy to biological products; West-Haven HE ≥ III ; Uncontrolled severe infections; HRS. Serum creatinine (Cr)>2×ULN, or Cr increase>50% during the screening period; Combined with other serious underlying diseases. Organ transplant recipients; Child-bearing females. Pregnancy test positive. Refusing to take contraceptive measures; (8) Participation in other clinical trials. Using study drugs within three month; (9) With the following laboratory test abnormality: PLT<30×109/L, HGB<70 g/L; ALT and (or) AST> 5×ULN, TBIL>3×ULN; Prothrombin activity <40%, PT prolonged>5s; LVEF <50%; The 24h urine volume exceeds 1500 mL/day ; 10) Other subjects by investigator's opinion.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: active comparator：HumanAlbumin<br>Participants received HumanAlbumin 10g/d | Drug: HumanAlbumin<br>* Participants will receive HumanAlbumin of intravenous infusion<br>* Other names: Intravenous infusion of recombinant human albumin injection;|
| Experimental: Experimental:Recombinant Human Albumin Injection 10g<br>Participants received Recombinant Human Albumin Injection 10g/d | Drug: Recombinant Human Albumin Injection<br>* Participants will receive Recombinant Human Albumin Injection of intravenous infusion<br>* Other names: Intravenous infusion of human albumin injection;|
| Experimental: Experimental:Recombinant Human Albumin Injection 20g<br>Participants received Recombinant Human Albumin Injection 20g/d | Drug: Recombinant Human Albumin Injection<br>* Participants will receive Recombinant Human Albumin Injection of intravenous infusion<br>* Other names: Intravenous infusion of human albumin injection;|
| Experimental: Experimental:Recombinant Human Albumin Injection 30g<br>Participants received Recombinant Human Albumin Injection 30g/d | Drug: Recombinant Human Albumin Injection<br>* Participants will receive Recombinant Human Albumin Injection of intravenous infusion<br>* Other names: Intravenous infusion of human albumin injection;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerance | Incidence and severity of adverse events | Day 1-Day 14（approximately，After the treatment） | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major efficacy character: Albumin concentration change | Albumin concentration change from baseline to Day 14（approximately，After the treatment） | Day 1-Day 14（approximately，After the treatment） | 
| Efficacy：Ascites regression rate | Ascites regression rate from baseline at Day 14（approximately，After the treatment） | Day 1-Day 14（approximately，After the treatment） | 
| Efficacy：Ascites resolution time | Ascites resolution time | Day 1-Day 14（approximately，After the treatment） | 
| Efficacy： HRS (hepato-renal syndrom) | Incidence of HRS | Day 1-Day 14（approximately，After the treatment） | 
| Efficacy： OHE(overt hepatic encephalopathy) | Incidence of OHE | Day 1-Day 14（approximately，After the treatment） | 
| Efficacy： abdominal circumference | Change of abdominal circumference from baseline at Day 14（approximately，After the treatment） | Day 1-Day 14（approximately，After the treatment） | 
| Efficacy：Weight | Change of Weight from baseline at Day 14（approximately，After the treatment） | Day 1-Day 14（approximately，After the treatment） | 
| Pharmacodynamic parameters | Plasma colloidal osmotic pressure change from baseline | Day 1-Day 29 | 
| PK parameters | Maximum Plasma Concentration（Cmax）of ALB as Recombinant Human Albumin administration occur | Day 1-Day 29 | 
| PK parameters | Time to Maximum Plasma Concentration（Tmax）of ALB as Recombinant Human Albumin administration occur | Day 1-Day 29 | 
| PK parameters | Half life (t1/2）as Recombinant Human Albumin administration occur | Day 1-Day 29 | 
| PK parameters | Area under the curve(AUC) as Recombinant Human Albumin administration occur | Day 1-Day 29 | 
| Immunogenicity | Percentage of patients with positive reaction against human albumin | Day 1-Day 29 |