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

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

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

Study Overview

• Status: Unknown
• Conditions: HBeAg Positive Chronic Hepatitis B
• Intervention / Treatment: Drug: Anti-HBV placenta transfer factor injection; Other: Placebo

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 Type: Interventional
• Enrollment (Anticipated): 288
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental Group; 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; 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
Placebo Comparator: Comparator Group; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Shineway Pharmaceutical Co.,Ltd
• Investigators: Study Chair: Guiqiang Wang, Doctor, Peking University First Hospital; Principal Investigator: Maorong Wang, Doctor, China People's Liberation Army No. Eight One Hospital; Principal Investigator: Zheling Wang, Doctor, Qingdao Infectious Diseases Hospital; Principal Investigator: Zhiqiang zou, Doctor, Yantai Infectious Diseases Hospital; Principal Investigator: Peili Zhao, Doctor, The Third Hospital of Qinhuangdao City; Principal Investigator: Dexing Jia, Doctor, Weifang people's Hospital; Principal Investigator: Zhenghua Zhao, Doctor, Tai'an Central Hospital; Principal Investigator: Feng Gao, Doctor, Linyi People's Hospital; Principal Investigator: Sikui Wang, Doctor, Liaocheng People's Hospital; Principal Investigator: lingdao Huo, Doctor, The Third People's Hospital of Taiyuan; Principal Investigator: Yuping Ma, Doctor, Xi'an Eighth Hospital; Principal Investigator: Hongxu Zhang, Doctor, Luohe Central Hospital; Principal Investigator: Xu Zhang, Doctor, General Hospital of Ningxia Medical University

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Anticipated): December 1, 2016
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: March 10, 2015
• First Submitted That Met QC Criteria: April 5, 2015
• First Posted (Estimate): April 9, 2015

Study Record Updates

• Last Update Posted (Estimate): April 9, 2015
• Last Update Submitted That Met QC Criteria: April 5, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Keywords: HBeAg positive chronic hepatitis B; HBeAg serum conversion rate; HBeAg serum disappearance rate; HBeAg and HBsAg titer
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: SW002