Phase II/III Clinical Trial of Recombinant Human Serum Albumin in Cirrhotic Patients With Ascites

Random, Double-blind, Parallel Group Phase II/III Clinical Trial to Evaluate the Effectiveness and Safety of Recombinant Human Serum Albumin Versus Human Serum Albumin in Hepatic Cirrhosis Patients With Ascites

This trial adopts random, double-blind, positive control, parallel group design to evaluate the effectiveness and safety of recombinant human serum albumin versus human serum albumin in hepatic cirrhosis patients with ascites.

Study Overview

• Status: Completed
• Conditions: Cirrhotic Ascites
• Intervention / Treatment: Drug: Recombinant Human Serum Albumin; Drug: Human Serum Albumin

Detailed Description

This trial adopts random, double-blind, positive control, parallel group design to evaluate the effectiveness and safety of recombinant human serum albumin versus human serum albumin in hepatic cirrhosis patients with ascites.

In this trial（phase III）, the efficacy of rHSA will be evaluated by the change in serum albumin concentration immediately after the last intravenous administration from baseline, and its safety, PD characteristics and immunogenicity will be further evaluated.

• Study Type: Interventional
• Enrollment (Actual): 390
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Xuancheng, Anhui, China, 242000
      • Xuancheng People's Hospital
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100000
      • Beijing Friendship Hospital, Capital Medical University
    • Beijing, Beijing Municipality, China, 100000
      • Beijing Youan Hospital, Capital Medical University
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 404100
      • Chongqing University Three Gorges Hospital
  • Guangdong
    • Foshan, Guangdong, China, 528000
      • Shunde Hospital of Southern Medical University
    • Guangzhou, Guangdong, China, 510000
      • Guangzhou Eighth People's Hospital, Guangzhou Medical University
    • Huizhou, Guangdong, China, 516000
      • Huizhou First Hospital
    • Huizhou, Guangdong, China, 516000
      • Huizhou Central People's Hospital
    • Shenzhen, Guangdong, China, 518000
      • ShenZhen People's Hospital
    • Shenzhen, Guangdong, China, 518000
      • Shenzhen Protgen Co., Ltd.
  • Guizhou
    • Guiyang, Guizhou, China, 550000
      • Guizhou Provincial People's Hospital
    • Zunyi, Guizhou, China, 563000
      • Affiliated Hospital of Zunyi Medical University
  • Hebei
    • Shijiangzhuang, Hebei, China, 050000
      • Shijiangzhuang Fifth Hospital
    • Shijiazhuang, Hebei, China, 050000
      • Hebei medical university third hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • The Fourth Affiliated Hospital of Harbin Medical University
  • Henan
    • Kaifeng, Henan, China
      • The First Affiliated Hospital of Henan University
    • Luoyang, Henan, China, 471000
      • Luoyang Central Hospital
    • Luoyang, Henan, China, 471000
      • Luoyang Third People's Hospital
    • Puyang, Henan, China, 457000
      • Puyang Oilfield General Hospital
    • Xinyang, Henan, China, 464000
      • Xinyang Central Hospital
    • Zhengzhou, Henan, China, 450000
      • People's Hospital of Zhengzhou
    • Zhengzhou, Henan, China, 450000
      • Zhengzhou Central Hospital
    • Zhengzhou, Henan, China, 450000
      • The Sixth People's Hospital of Zhengzhou
    • Zhoukou, Henan, China, 466000
      • Zhoukou Central Hospital
  • Hubei
    • Shiyan, Hubei, China, 442000
      • Taihe Hospital
    • Shiyan, Hubei, China, 442000
      • Sinopharm Dongfeng General Hospital
    • Wuhan, Hubei, China, 430000
      • The Central Hospital of Wuhan
    • Yichang, Hubei, China, 443000
      • Yichang Central People's Hospital
  • Hunan
    • Changde, Hunan, China, 415000
      • The First People's Hospital of Changde City
    • Changsha, Hunan, China, 410005
      • The First Hospital of Changsha
    • Changsha, Hunan, China, 410000
      • Changsha Central Hospital
    • Changsha, Hunan, China, 410000
      • The First Hospital of Hunan University of Chinese Medicine
    • Chenzhou, Hunan, China, 423000
      • First People's Hospital of Chenzhou
    • Hengyang, Hunan, China, 421000
      • The First Affiliated Hospital of University of South China
    • Hengyang, Hunan, China, 421000
      • Central Hospital of Hengyang
    • Huaihua, Hunan, China, 418000
      • Hunan University of Medicine General Hospital
    • Loudi, Hunan, China, 417000
      • Loudi Central Hospital
    • Xiangtan, Hunan, China, 411100
      • The Central Hospital of Xiangtan
    • Yiyang, Hunan, China, 413000
      • Yiyang Central Hospital
    • Yueyang, Hunan, China, 414000
      • The Third People's Hospital of Hunan Provincial
    • Zhuzhou, Hunan, China, 412000
      • ZhuZhou Central Hospital
  • Jiangxi
    • Ganzhou, Jiangxi, China, 341000
      • First Affiliated Hospital of Gannan Medical University
    • Jiujiang, Jiangxi, China, 332000
      • Jiujiang No.1 People's Hospital
    • Jiujiang, Jiangxi, China, 332000
      • Jiujiang Third People's Hospital
    • Nanchang, Jiangxi, China, 330000
      • The Second Affiliated Hospital of Nanchang University
    • Nanchang, Jiangxi, China, 330000
      • The First Affiliated Hospital of Nanchang University
    • Nanchang, Jiangxi, China, 330000
      • Jiangxi Provincial People's Hospital
    • Nanchang, Jiangxi, China, 330000
      • The Ninth Hospital of Nanchang
    • Pingxiang, Jiangxi, China, 337000
      • Pingxiang People's Hospital
    • Pingxiang, Jiangxi, China, 337000
      • Pingxiang No.2 People's Hospital
  • Jilin
    • Tonghua, Jilin, China, 135099
      • Meihekou Central Hospital
  • Shandong
    • Jinan, Shandong, China, 250000
      • Shandong Public Health Clinical Center
  • Sichuan
    • Yibin, Sichuan, China, 644000
      • The Second People's Hospital of Yibin
  • Yunnan
    • Kunming, Yunnan, China, 650000
      • The Second Affiliated Hospital of Kunming Medical University
    • Kunming, Yunnan, China, 650000
      • The First People's Hospital of Yunnan Province
    • Kunming, Yunnan, China, 650000
      • The Third People's Hospital of Kunming city
  • Zhejiang
    • Wenzhou, Zhejiang, China, 325000
      • The First Affiliated Hospital of Wenzhou Medical University
    • Wenzhou, Zhejiang, China, 325000
      • Wenzhou Central Hospital
    • Wenzhou, Zhejiang, China, 325000
      • The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University
    • Wenzhou, Zhejiang, China, 325000
      • The Third Affiliated Hospital of Wenzhou Medical University
    • Wenzhou, Zhejiang, China, 325000
      • Zhejiang Chinese Medical University Affiliated Wenzhou Hospital of Traditional Chinese Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Agree to follow the experimental treatment plan and visit schedule, voluntarily join the group, and sign a written informed consent form;
2. On the day of signing the informed consent form, the age is between 18 and 70 years old, and there is no gender limit; Body mass index (BMI) within the range of 17.0-29.0 kg/m² (including boundary values);
3. Patients diagnosed clinically with decompensated liver cirrhosis ascites, and confirmed by abdominal ultrasound examination during screening to have ascites grading of 1-2, while meeting the requirement of serum albumin (ALB)<30 g/L;
4. Men with fertility and women of childbearing age (women of childbearing age include premenopausal women and women within two years after menopause) are willing to take effective contraceptive measures (condoms, contraceptive sponges, contraceptive gel, contraceptive membranes, intrauterine devices, oral or injectable contraceptives, subcutaneous implants, etc.) within three months after the last administration of the trial drug from the date of signing the informed consent; Women of childbearing age must have a negative pregnancy test result within ≤ 7 days before the first trial drug administration.

Exclusion Criteria:

1. Individuals with a known history of allergies/allergic reactions to yeast or yeast derived products, or those who are allergic to any component of the study formulation; Individuals with an allergic constitution (multiple drug or food allergies) or a history of allergies to biological products, as well as a history of severe systemic allergic reactions caused by other reasons and deemed unsuitable for treatment with the investigational drug by the researcher;
2. During the screening process, there were serious digestive system diseases and complications that the researchers deemed unsuitable for participation in this study, including but not limited to malignant ascites, diagnosis of grade III or IV hepatic encephalopathy according to the West Haven grading criteria, portal vein cancer thrombus/thrombus, circulatory dysfunction after abdominal puncture, biliary obstructive disease determined by ultrasound or other imaging examinations, gastrointestinal bleeding that stopped bleeding after treatment for less than 10 days or endoscopic ligation could not effectively stop bleeding, or those assessed by the researchers as having a high risk of bleeding during the trial period (such as severe esophagogastric varices with positive red sign on gastroscopy within 3 months before screening);
3. When screening, there is a history of active cardiovascular disease or other conditions that researchers determine are not suitable for receiving human serum albumin treatment, including but not limited to hypertension (systolic blood pressure>140 mmHg or diastolic blood pressure>90 mmHg, except for those determined by researchers to have good medication control and stable condition), severe anemia, acute heart disease, severe cardiovascular or structural heart disease, severe arrhythmia, decompensated heart failure (normal blood volume or high blood volume), unstable angina pectoris, myocardial infarction in the past 6 months before screening, tachycardia/bradycardia requiring medication treatment, third degree atrioventricular block, etc;
4. Active metabolic system disease or medical history (except for diabetes patients with stable blood glucose control as judged by the investigator), or combined with renal function injury, which is not suitable for serum albumin treatment as judged by the investigator;
5. When screening, there were serious underlying diseases that the researchers deemed unsuitable for participation in this study, including but not limited to active malignant tumors (including hepatocellular carcinoma [HCC]), pulmonary edema, bleeding tendency or active bleeding disease, uncontrolled infections (including active spontaneous bacterial peritonitis [SBP1]), thyroid dysfunction (according to the National Cancer Institute's Common Terminology Criteria for Adverse Events INCICTCAEI 5.0 grade 3 or above), pleural effusion that the researchers determined may require treatment or have disease changes throughout the entire trial process, etc;
6. The patient has the following laboratory test abnormalities: (1) Bone marrow function: Absolute neutrophil count (ANC)<1.0x10 ^ 9/L; Platelets (PLT)<20x10 ^ 9/L; Hemoglobin (HGB)<70gL; (2) Liver function: Alanine aminotransferase (ALT)>5 × ULN (upper limit of normal); Aspartate aminotransferase (AST)>5 × ULN; Serum bilirubin (TBIL)>4 x upper limit of normal (ULN) or deemed unsuitable for participation in the trial by the researcher; (3) Renal function: serum creatinine>3 times the upper limit of normal (ULN), positive urine protein, and the researcher's judgment that it is not suitable to participate in the trial; (4) Coagulation function: prothrombin time (PT) prolonged>5s；
7. Individuals who have received human plasma preparations (including human albumin preparations) within 7 days prior to the first administration of the investigational drug; Individuals with a history of organ transplantation; Those who need to undergo or plan invasive invasive examinations or treatments during the research period;
8. Participated in or was participating in clinical trials of other new drugs or medical devices within 30 days prior to screening, and used the investigational drug/treatment provider;
9. Individuals who test positive for human immunodeficiency virus (HIV) antibodies;
10. Pregnant or lactating women;
11. Other reasons why researchers believe it is not suitable to participate in this study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; The experimental drug was administered at a dose of 20 g/ day for 7 days.	Drug: Recombinant Human Serum Albumin; The experimental drug was administered at a dose of 20 g/ day for 7 days.
Active Comparator: Group 2; The positive control drug was administered at a dose of 20 g/ day for 7 days.	Drug: Human Serum Albumin; The positive control drug was administered at a dose of 20 g/ day for 7 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of serum albumin concentration	The change in serum albumin concentration confirmed by albumin examination immediately after the completion of secondary intravenous administration compared to baseline (based on the results of central laboratory tests)	7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in serum albumin concentration immediately after completion of the last intravenous dose, as confirmed by albumin testing at the local laboratory	The change in serum albumin concentration confirmed by local laboratory albumin test immediately after the last intravenous administration compared to baseline	7 days
Changes in the depth of ascites	Changes in ascites depth from baseline upon completion of the last intravenous administration	7 days
The proportion of subjects with serum albumin concentration ≥ 35 g/L	The proportion of subjects whose serum albumin concentration confirmed by albumin examination at the completion of the last intravenous administration is ≥ 35 g/L	7 days
The time when serum albumin concentration reached ≥35 g/L	The time when serum albumin concentration reached ≥35 g/L	90 days
Changes in abdominal circumference	Changes in abdominal circumference compared to baseline at the completion of the last intravenous administration	7 days
Changes in body weight	Changes in body weight compared to baseline at the completion of the last intravenous administration	7 days
The change in serum albumin concentration during the re-treatment period	The change in serum albumin concentration confirmed by albumin examination immediately after the completion of the last intravenous administration during the re-treatment period compared to the baseline before the re-treatment	7 days
The improvement rate of ascites during the re-treatment period	The improvement rate of ascites at the completion of the last intravenous administration during the re-treatment period	7 days
Changes in the depth of ascites during the re-treatment period	Changes in ascites depth at the completion of the last intravenous administration during the re-treatment period compared to baseline before the re-treatment	7 days
The proportion of subjects with serum albumin concentration ≥ 35 g/L during the re-treatment period	Proportion of subjects with serum albumin concentration ≥ 35 g/L confirmed by albumin examination during the re-treatment period	7 days
The time when serum albumin concentration reached ≥35 g/L during the re-treatment period	The time when the serum albumin concentration confirmed by the albumin test during the re-treatment period reaches ≥ 35 g/L	7 days
Changes in abdominal circumference during the re-treatment period	Changes in abdominal circumference at the completion of the last intravenous administration during the re-treatment period compared to baseline before the re-treatment	7 days
Changes in body weight during the re-treatment period	Changes in body weight at the completion of the last intravenous administration during the re-treatment period compared to baseline before the re-treatment	7 days
Key Secondary Outcome Measures: The improvement rate of ascites	The improvement rate of ascites at the completion of the last intravenous administration	7 days

Collaborators and Investigators

• Sponsor: Protgen Ltd
• Investigators: Study Director: Jidong Jia, Ph.D, Beijing Friendship Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 19, 2024
• Primary Completion (Actual): May 14, 2025
• Study Completion (Actual): May 14, 2025

Study Registration Dates

• First Submitted: August 11, 2024
• First Submitted That Met QC Criteria: August 11, 2024
• First Posted (Actual): August 14, 2024

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: March 7, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Ascites; Amino Acids, Peptides, and Proteins; Proteins; Blood Proteins; Albumins; Serum Albumin; recombinant human serum albumin-heme; Serum Albumin, Human
• Other Study ID Numbers: rHSA 2020-3 (Phase Ⅲ)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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