Clinical trial NCT02412319: The Clinical Trial of the Anti Hepatitis B Placenta Transfer Factor Injection
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: HBeAg Positive Chronic Hepatitis B
Keywords: HBeAg positive chronic hepatitis B
HBeAg serum conversion rate
HBeAg serum disappearance rate
HBeAg and HBsAg titer
Lead sponsor: Shineway Pharmaceutical Co.,Ltd
Sponsor class: INDUSTRY
First posted: 2015-04-09
Enrollment: 288
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: HBeAg serum conversion rate
timeFrame: Week 48
Secondary outcomes:
measure: HBeAg serum conversion rate
timeFrame: Week 24, 72
measure: HBeAg disappearance rate
timeFrame: Week 24, 48 and 72
measure: HBV DNA titer
timeFrame: Week-4, 0,12,24,48,72 and 96
measure: The proportion of subjects for the HBV DNA can not be detected
timeFrame: Week 24, 48 and 72
measure: HBeAg and HBsAg titer
timeFrame: Week-4, 0,12,24,48,72 and 96
measure: The quantitative changes of anti -HBc
timeFrame: Week-4, 0,12,24,48,72 and 96
measure: The variation of ALT
timeFrame: Week-4,24,48,72 and 96
measure: The seroconversion rate of HBsAb and HBeAb
timeFrame: Week-4, 0,12,24,48,72 and 96
measure: The resistance mutation rate of HBsAb and HBeAb
timeFrame: Week-4, 0,12,24,48,72 and 96
measure: The cumulative incidence of virologic breakthroughrate of HBsAb and HBeAb
timeFrame: Week-4, 0,12,24,48,72 and 96
measure: The changes of relative immune parameters of the transfer factor in peripheral blood(the number of T lymphocytes and the expression levels of cytokines)
timeFrame: Week 0, 12, 24, 48, 72, 96
Other outcomes:
Locations:
Study officials:
affiliation: Peking University First Hospital
name: Guiqiang Wang, Doctor
role: STUDY_CHAIR
affiliation: China People's Liberation Army No. Eight One Hospital
name: Maorong Wang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Qingdao Infectious Diseases Hospital
name: Zheling Wang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Yantai Infectious Diseases Hospital
name: Zhiqiang zou, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Third Hospital of Qinhuangdao City
name: Peili Zhao, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Weifang People's Hospital
name: Dexing Jia, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Tai'an Central Hospital
name: Zhenghua Zhao, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Linyi People's Hospital
name: Feng Gao, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Liaocheng People's Hospital
name: Sikui Wang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: The Third People's Hospital of Taiyuan
name: lingdao Huo, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Xi'an Eighth Hospital
name: Yuping Ma, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: Luohe Central Hospital
name: Hongxu Zhang, Doctor
role: PRINCIPAL_INVESTIGATOR
affiliation: General Hospital of Ningxia Medical University
name: Xu Zhang, Doctor
role: PRINCIPAL_INVESTIGATOR
References: