Hepatitis B virus (HBV) infection is a worldwide health problem. It has been proved that the persistence of HBV is associated with the failure to stimulate an efficient HBV-specific immune response. T101, the Chinese counterpart of TG1050, is a replication-defective adenovirus serotype 5 (Ad5) expressing multiple HBV-specific antigens (core, polymerase and envelope) and is used as therapeutic vaccine for chronic hepatitis B patients. The application of T101 aims at inducing a broad HBV-specific cellular immune response and ultimately eliminating HBV infection.
This study is a randomized, double-blind, placebo-controlled, single dose (SD) and multiple dose (MD) administration study. Primary Objective: Safety and tolerability; Secondary Objective: 1. Antiviral activity of T101 (HBsAg levels). 2. Cellular (HBV-specific) and humoral (AD5 neutralizing antibodies, NAd5) immune responses to T101. Key Inclusion Criteria: 1. Chronic hepatitis B patients with positive HBsAg. 2. Patients must be receiving antiviral treatment with nucleoside analogs and have negative HBV DNA (defined as HBV DNA \<20 IU/mL).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
36
Single Dose (SD) Cohort: In each group, 3 of chronic hepatitis B patients will be subcutaneously injected with different dose level of T101 at 1.0E+9VP (Group1)/1.0E+10VP (Group2)/1.0E+11VP (Group 3) on D1. Multiple Dose (MD) Cohort: In each group, 9 of chronic hepatitis B patients will be subcutaneously injected with different dose level of T101 at 1.0E+10VP (Group1)/1.0E+11VP (Group2) on D1, D8, D15.
Single Dose (SD) Cohort: 3 of chronic hepatitis B patients will be subcutaneously injected with placebo on D1. Multiple Dose (MD) Cohort: 6 of chronic hepatitis B patients will be subcutaneously injected with placebo on D1, D8, D15.
The First Hospital of Jilin University
Changchun, China
Adverse events
Observe all the adverse events of all patients, record their clinical features, severity, time of occurence, end time, duration, treatment measures, recovery and determine their correlation with T101
Time frame: through study completion, an average of 1 year
Vital signs index
vital signs measure: include body temperature, pulse rate, respiratory rate and blood pressure, to observe whether there are abnormal index, especially whether there are abnormal index caused by acute allergic reaction.
Time frame: Single Dose Group: baseline, Day-1, Day1, Day8, Day15, Day2ine9; Multiple Dose Group: baseline, Day-1, Day7, Day8, Day14, Day15, Day22, Day29, Day43, Day71, Day99.
Routine blood test
Observe the blood routine tests results of all patients, compare the change of each index before and after the treatment, and determine their correlation with T101 if abnormal index occur.
Time frame: Single Dose Group: baseline, Day-1, Day8, Day15, Day29; Multiple Dose Group: baseline, Day-1, Day7, Day14, Day22, Day29, Day43, Day71, Day99, Day 197, Day379.
Blood biochemical test
Observe the blood biochemical tests results of all patients, compare the change of each index before and after the treatment, and determine their correlation with T101 if abnormal index occur.
Time frame: Single Dose Group: baseline, Day-1, Day8, Day15, Day29; Multiple Dose Group: baseline, Day-1, Day7, Day14, Day22, Day29, Day43, Day71, Day99, Day 197, Day379.
Coagulation function test
Observe the coagulation function tests results of all patients, compare the change of each index before and after the treatment, and determine their correlation with T101 if abnormal index occur.
Time frame: Single Dose Group: baseline, Day-1, Day8, Day15, Day29; Multiple Dose Group: baseline, Day-1, Day7, Day14, Day22, Day29, Day43, Day71, Day99, Day 197, Day379.
Routine urinalysis
Observe the routine urinalysis tests results of all patients, compare the change of each index before and after the treatment, and determine their correlation with T101 if abnormal index occur.
Time frame: Single Dose Group: baseline, Day-1, Day8, Day15, Day29; Multiple Dose Group: baseline, Day-1, Day7, Day14, Day22, Day29, Day43, Day71, Day99, Day 197, Day379.
HBsAg quantitative levels
Evaluate the efficacy of T101
Time frame: Single Dose Group: Day1, Day29; Multiple Dose Group: Day1, Day29, Day43, Day71, Day99, Day197, Day379.
HBeAg quantitative levels
Evaluate the efficacy of T101
Time frame: Single Dose Group: Day1, Day29; Multiple Dose Group: Day1, Day29, Day43, Day71, Day99, Day197, Day379.
Ad5 neutralizing antibodies
Use Analysis of luciferase Ad5 neutralizing antibody method to evaluate the changes of NAd5 titers after T101 administration
Time frame: Single Dose Group: Day1, Day15, Day29; Multiple Dose Group: Day1, Day29, Day43, Day71, Day99, Day197, Day379.
Cellular and humoral immune responses
Detect the T-cell responses by interferon-γ(INF-γ) ELISPOT
Time frame: Single Dose Group: Day1, Day15, Day29; Multiple Dose Group: Day1, Day29, Day43, Day71, Day99, Day197, Day379.
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