The Clinical Trial of the Anti Hepatitis B Placenta Transfer Factor Injection

Study Overview
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Brief Summary
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Asses the efficacy and safety of the Anti hepatitis B placenta transfer factor injection in the treatment of HBeAg positive chronic hepatitis B.

Detailed Description
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This study using entecavir tablets as basic therapy, is a randomized, double-blind, placebo-controlled multi center study, including the screening period (-4 weeks), baseline and treatment period (96 weeks). The treatment period of first 48 weeks, using entecavir tablets as basic treatment, placebo-controlled trials; the second 48 weeks, taking entecavir tablets alone, continue observation experiment.

Official Title
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The Efficacy and Safety of the Anti Hepatitis B Placenta Transfer Factor Injection in the Treatment of HBeAg Positive Chronic Hepatitis B, Randomized, Double Blind, Placebo Controlled, Multi Center Clinical Trial

Conditions
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HBeAg Positive Chronic Hepatitis B

Intervention / Treatment
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* Drug: Anti-HBV placenta transfer factor injection
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: aged 18-65, sex not limited; patients with HBeAg positive chronic hepatitis B: Screening HBsAg positive for more than 6 months; screening HBeAg positive; screening serum HBV DNA≥1.0×105U/ml； 2 * ULN (2 times the upper limit of normal value) < ALT <10 * ULN (10 times the upper limit of normal value);; total bilirubin <51μmol/L; hepatitis B virus resistance gene sequencing negative; agree in the process of the study, do not participate in any other clinical studies or other anti HBV therapy; before the beginning of the study, understand and sign the informed consent form approved by the ethics committee, and cooperate to conduct clinical research according to the requirements for the study. Exclusion Criteria: by the following evidences prompt suspected hepatocellular carcinoma: B ultrasound or imaging examination discover occupying lesion;B ultrasound normal but serum alpha fetoprotein (AFP) level has a continuous increasing trend; AFP > 100ng/ml, and after review, still so. with liver disease acute exacerbation cause a transient liver function decompensation disease or baseline with clinical performance of decompensated liver disease; serum creatinine ≥1.5mg/dl (≥130μmol/l); the serum amylase > 2 times the normal reference upper limit value; hemoglobin (male <100g/L, female <90g/L), white blood cell< 3.5* 109/L, platelet< 60 * 109/L; combined with infection of HCV (anti -HCV positive), HIV, anti -HAV IgM positive, anti -HDV IgM positive, anti -HEV IgM positive, anti -EBV IgM positive, anti -CMV IgM positive, autoimmune hepatitis(such as the titer of anti nuclear antibody> 1:160) or activite liver disease caused by other known or unknown reason; investigators consider that may interfere with the treatment,evaluation or compliance of the subjects, including any uncontrolled clinical significance of kidneys, heart, lungs, blood vessels, neurogenic, digestive system, metabolic diseases (diabetes, hyperthyroidism, adrenal disease), immune function disorder or tumor; subjects with a history of alcoholism or drug abuse,investigators consider the subjects cannot comply with this protocol or affect the results analysis; pregnancy,lactation or female subjects plan to conceive or the companions of male subjects plan to conceive during the study 6 months before the study medication used immunosuppressants,immunomodulators(thymosin alpha), cytotoxic drugs; 6 months before the study medication used anti HBV drug therapy (interferon, Lamivudine, Adefovir, Entecavir and Telbivudine, Tenofovir,etc); plan or have had liver transplantation; received other study drug treatment within 3 months prior to screening; drug allergy history or allergic for Nucleoside or Nucleotide drug; the subjects non compliance with the protocol or subjects exist any situation which investigators considered not suitable for participation in this study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Experimental Group<br>Anti-HBV Placenta Transfer Factor Injection: 2mg/4ml, intramuscular injection, the 0-24 week, once every other day; week 24-48, 2 times / week; entecavir tablets: 0.5mg/ tablet / time, daily bedtime fasting oral once, treatment course 96 weeks | Drug: Anti-HBV placenta transfer factor injection<br>* Anti-HBV Placenta Transfer Factor Injection: 2mg/4ml, intramuscular injection, the 0-24 week, once every other day; week 24-48, 2 times / week; entecavir tablets: 0.5mg/ tablet / time, daily bedtime fasting oral once, treatment course 96 weeks<br>|
| Placebo Comparator: Comparator Group<br>Physiological saline injection: 2mg/4ml, intramuscular injection,the 0-24 week, once every other day, week 24-48, 2 times / week; entecavir tablets: 0.5mg/ tablet / time, daily bedtime fasting oral once, treatment course 96 weeks | Other: Placebo<br>* Physiological saline injection: 2mg/4ml, intramuscular injection,the 0-24 week, once every other day, week 24-48, 2 times / week; entecavir tablets: 0.5mg/ tablet / time, daily bedtime fasting oral once, treatment course 96 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBeAg serum conversion rate | The HBeAg serum conversion rate of the Test Group and the Control Group after 48 weeks treatment | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBeAg serum conversion rate | The HBeAg serum conversion rate of the Test Group and the Control Group for treatment week 24, week 72 | Week 24, 72 | 
| HBeAg disappearance rate | The HBeAg disappearance rate of the Test Group and the Control Group for treatment week 24, week 48 and week 72 | Week 24, 48 and 72 | 
| HBV DNA titer | The proportion of subjects for each observation point in HBV DNA titer decreased 2 logarithmic | Week-4, 0,12,24,48,72 and 96 | 
| The proportion of subjects for the HBV DNA can not be detected | The proportion of subjects for the HBV DNA can not be detected in treatment week 24, week 48 and week 72 | Week 24, 48 and 72 | 
| HBeAg and HBsAg titer | The changes of HBeAg and HBsAg titer at each observation point | Week-4, 0,12,24,48,72 and 96 | 
| The quantitative changes of anti -HBc | The quantitative changes of anti -HBc in each observation point | Week-4, 0,12,24,48,72 and 96 | 
| The variation of ALT | The variation of ALT in each observation point | Week-4,24,48,72 and 96 | 
| The seroconversion rate of HBsAb and HBeAb | The seroconversion rate of HBsAb and HBeAb in each observation point | Week-4, 0,12,24,48,72 and 96 | 
| The resistance mutation rate of HBsAb and HBeAb | The resistance mutation ncidence of HBsAb and HBeAb in each observation point | Week-4, 0,12,24,48,72 and 96 | 
| The cumulative incidence of virologic breakthroughrate of HBsAb and HBeAb | The cumulative incidence of virologic breakthroughrate of HBsAb and HBeAb in each observation point | Week-4, 0,12,24,48,72 and 96 | 
| The changes of relative immune parameters of the transfer factor in peripheral blood(the number of T lymphocytes and the expression levels of cytokines) | The changes of relative immune parameters of the transfer factor in peripheral blood | Week 0, 12, 24, 48, 72, 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HBeAg positive chronic hepatitis B, HBeAg serum conversion rate, HBeAg serum disappearance rate, HBeAg and HBsAg titer