This trial adopts a randomized, double-blind, positive drug-controlled, dose-escalated phase Ib clinical study evaluating the safety, tolerability, pharmacokinetic characteristics and preliminary effectiveness of recombinant human serum albumin in patients with liver cirrhosis and ascites subjects (both male and female) were screened and enrolled to the three dose levels of 10g, 20 g,and 30 g according to the principle of dose escalation, and 8 out of 12 subjects in each dose group One patient received the test drug, and 4 received a positive drug.
In this Phase Ib clinical trial, randomized, double-blind, positive-controlled, dose-increasing design was employed to enroll cirrhosis ascites patients and evaluate safety, tolerability, PK characteristics, PD characteristics and preliminary efficacy at different dose levels of recombinant human serum albumin. Three dose groups (10 g/day, 20 g/day, 30 g/day) were set up in this study, and they were escalated from the lowest to the highest dosage. It is planned to enroll 12 subjects in each dose group, with 8 of 12 subjects in each dose group receiving the investigational product and 4 of 12 subjects receiving the comparator product intravenously once a day for 14 days or up to serum albumin ≥ 35 g/L ( whichever occurs first ), to investigate the safety, tolerability, immunogenicity, PK characteristics, PD characteristics and preliminary efficacy in repeated usage of recombinant human serum albumin.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
36
10 g/bottle (20%, 50 mL)
10 g/bottle (20%, 50 mL)
Shenzheng Protgen Ltd
Guangdong, Shenzheng, China
TEAE
Adverse events will be coded using MedDRA (International Dictionary of Medical Terms)., TEAEs related to test drugs were summarized and analyzed according to SOC and PT, and the number of occurrences and the incidence were calculated.
Time frame: 57 days
SAE
Adverse events will be coded using MedDRA (International Dictionary of Medical Terms). SAEs related to test drugs were summarized and analyzed according to SOC and PT, and the number of occurrences and the incidence were calculated.
Time frame: 57 days
AUC0-last
Within 1 hour before administration of D1, immediately after administration (+1 min), 2 hours (±5 minutes), 10 hours (±30 minutes); If subject has completed 14 days of treatment, then: Within 1 hour before administration of D2\~D13, immediately after administration (+1 min); D14: within 1 hour before administration, immediately after administration (+1 min), 2 hours (±5 minutes), 10 hours (±30 minutes); D15, D16, D17, D29 (±3 days), D57 (±5 days). If the 14-day treatment has not been completed, then: Before drug withdrawal: receive 2 PK blood sample collections within 1 hour before administration and immediately after administration (+1 min) each day; After drug withdrawal: from the day of drug withdrawal, collect PK blood samples once for 3 consecutive days.
Time frame: 57 days
Pharmacokinetic characteristics
Within 1 hour before administration of D1, immediately after administration (+1 min), 2 hours (±5 minutes), 10 hours (±30 minutes); If subject has completed 14 days of treatment, then: Within 1 hour before administration of D2\~D13, immediately after administration (+1 min); D14: within 1 hour before administration, immediately after administration (+1 min), 2 hours (±5 minutes), 10 hours (±30 minutes); D15, D16, D17, D29 (±3 days), D57 (±5 days). If the 14-day treatment has not been completed, then: Before drug withdrawal: receive 2 PK blood sample collections within 1 hour before administration and immediately after administration (+1 min) each day; After drug withdrawal: from the day of drug withdrawal, collect PK blood samples once for 3 consecutive days.
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Time frame: 57 day
Albumin concentration of D15
Collect blood samples on the fifteenth day and determine the albumin concentration on the fifteenth day.
Time frame: 1 day
Albumin concentration of D29
Collect blood samples on the 29th day(±3 days) and determine the albumin concentration on the 29th day.
Time frame: 1 day
Albumin concentration of D57
Collect blood samples on the 57th day(±5 days) and determine the albumin concentration on the 57th day.
Time frame: 1 day
t1/2
Within 1 hour before administration of D1, immediately after administration (+1 min), 2 hours (±5 minutes), 10 hours (±30 minutes); If subject has completed 14 days of treatment, then: Within 1 hour before administration of D2\~D13, immediately after administration (+1 min); D14: within 1 hour before administration, immediately after administration (+1 min), 2 hours (±5 minutes), 10 hours (±30 minutes); D15, D16, D17, D29 (±3 days), D57 (±5 days). If the 14-day treatment has not been completed, then: Before drug withdrawal: receive 2 PK blood sample collections within 1 hour before administration and immediately after administration (+1 min) each day; After drug withdrawal: from the day of drug withdrawal, collect PK blood samples once for 3 consecutive days.
Time frame: 57 days
CL
Within 1 hour before administration of D1, immediately after administration (+1 min), 2 hours (±5 minutes), 10 hours (±30 minutes); If subject has completed 14 days of treatment, then: Within 1 hour before administration of D2\~D13, immediately after administration (+1 min); D14: within 1 hour before administration, immediately after administration (+1 min), 2 hours (±5 minutes), 10 hours (±30 minutes); D15, D16, D17, D29 (±3 days), D57 (±5 days). If the 14-day treatment has not been completed, then: Before drug withdrawal: receive 2 PK blood sample collections within 1 hour before administration and immediately after administration (+1 min) each day; After drug withdrawal: from the day of drug withdrawal, collect PK blood samples once for 3 consecutive days.
Time frame: 57 days
Cpost-Cpre
Calculate the ratio of serum albumin concentration to C0 at each time point, and calculate the difference of albumin concentration before and after each intravenous administration
Time frame: 14 days
Plasma colloid osmotic pressure
D1 within 1 hour before administration, immediately after administration (+1 min), 2 hours (±5 minutes), 10 hours (±30 minutes); If the 14-day treatment cycle is completed, then: Within 1 hour before administration of D2\~D13, immediately after administration (+1 min); D14: within 1 hour before administration, immediately after administration (+1 min), 2 hours (±5 minutes), 10 hours (±30 minutes); D15, D16, D17. If discontinuation of 14-day treatment cycle is not completed, then: Before drug withdrawal: 2 blood samples were collected within 1 hour before each administration and immediately after the administration (+1 min); After drug withdrawal: From the day of drug withdrawal, collect PD blood samples once for 3 consecutive days.
Time frame: 17 days
the Anti-Drug antibody (ADA) of rHSA
All subjects in this trial who received at least 1 intravenous dose, regardless of when they ended treatment, were required to visit D1 before intravenous administration of the investigational drug, D8, D15, D29, D57, and at the early withdrawal visit (if any). ADA blood samples were collected, and the sample collection time window was the same as the time window of the current visit. Immunogenicity was assessed by assessing the incidence and titers of anti-rHSA, if applicable.
Time frame: 57 days
the Anti-Drug antibody (ADA) of HCP
All subjects in this trial who received at least 1 intravenous dose, regardless of when they ended treatment, were required to visit D1 before intravenous administration of the investigational drug, D8, D15, D29, D57, and at the early withdrawal visit (if any). ADA blood samples were collected, and the sample collection time window was the same as the time window of the current visit. Immunogenicity was assessed by assessing the incidence and titers of anti-host protein (HCP) ADAs, if applicable.
Time frame: 57 days