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

Phase 4

• Conditions: HBeAg Positive Chronic Hepatitis B
• Interventions: Other: Placebo; Drug: Anti-HBV placenta transfer factor injection

• Registration Number: NCT02412319
• Lead Sponsor: Shineway Pharmaceutical Co.,Ltd

Brief Summary

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

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.

Study Timeline

• Study Start: 2014-10
• Study First Submitted: 2015-03-10
• Status Verified: 2015-04
• Study First Submitted QC: 2015-04-05
• Last Update Submitted: 2015-04-05
• Study First Posted: 2015-04-09
• Last Update Posted: 2015-04-09
• Primary Completion: 2016-12
• Study Completion: 2017-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 288

Inclusion Criteria

1. aged 18-65, sex not limited;
2. 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；
3. 2 * ULN (2 times the upper limit of normal value) < ALT <10 * ULN (10 times the upper limit of normal value);;
4. total bilirubin <51μmol/L;
5. hepatitis B virus resistance gene sequencing negative;
6. agree in the process of the study, do not participate in any other clinical studies or other anti HBV therapy;
7. 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

1. 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.
2. with liver disease acute exacerbation cause a transient liver function decompensation disease or baseline with clinical performance of decompensated liver disease;
3. serum creatinine ≥1.5mg/dl (≥130μmol/l);
4. the serum amylase > 2 times the normal reference upper limit value;
5. hemoglobin (male <100g/L, female <90g/L), white blood cell< 3.5* 109/L, platelet< 60 * 109/L;
6. 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;
7. 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;
8. subjects with a history of alcoholism or drug abuse,investigators consider the subjects cannot comply with this protocol or affect the results analysis;
9. pregnancy,lactation or female subjects plan to conceive or the companions of male subjects plan to conceive during the study
10. 6 months before the study medication used immunosuppressants,immunomodulators(thymosin alpha), cytotoxic drugs;
11. 6 months before the study medication used anti HBV drug therapy (interferon, Lamivudine, Adefovir, Entecavir and Telbivudine, Tenofovir,etc);
12. plan or have had liver transplantation;
13. received other study drug treatment within 3 months prior to screening;
14. drug allergy history or allergic for Nucleoside or Nucleotide drug;
15. the subjects non compliance with the protocol or subjects exist any situation which investigators considered not suitable for participation in this study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Comparator Group	Placebo	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
Experimental Group	Anti-HBV placenta transfer factor injection	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

Primary Outcome Measures

Name	Time	Method
HBeAg serum conversion rate	Week 48	The HBeAg serum conversion rate of the Test Group and the Control Group after 48 weeks treatment

Secondary Outcome Measures

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