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Phase 2 Trial of Therapeutic Hepatitis B Vaccine (Mimogen-based) for Chronic Hepatitis B

This study has been completed.
Sponsor:
Collaborator:
Third Military Medical University
Information provided by (Responsible Party):
Chongqing Jiachen Biotechnology Ltd.
ClinicalTrials.gov Identifier:
NCT00869778
First received: March 25, 2009
Last updated: November 20, 2016
Last verified: November 2016
  Purpose
The purpose is to evaluate efficacy and safety of therapeutic HBV vaccine (mimogen-based) treatment in chronic hepatitis B patients and to explore the most effective dosage and provide the rational for optimal dosing schedule.

Condition Intervention Phase
Chronic Hepatitis B
Biological: εPA-44
Other: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Phase II Clinical Trial to Evaluate the Efficacy and Safety of Therapeutic Hepatitis B Vaccine (Mimogen-based) in Treating Chronic Hepatitis B Patients

Resource links provided by NLM:


Further study details as provided by Chongqing Jiachen Biotechnology Ltd.:

Primary Outcome Measures:
  • Percentage of Participants With HBeAg Seroconversion at Endpoint [ Time Frame: Endpoint ]
    Primary endpoint data were summarised under "End of Study",using the last available post-baseline observation(Last Observation Carried Forward,LOCF)


Secondary Outcome Measures:
  • Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76 [ Time Frame: serology response at week 12, 28, 32, 40, 52, 64, 76 ]
    HBeAg seroconversion=HBeAg loss and presence of hepatitis B e antibody (HBeAb). HBeAg is a hepatitis B viral protein and is an indicator of active viral replication

  • The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale; [ Time Frame: week 12, 28, 32, 40, 52, 64, 76 ]
  • Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76 [ Time Frame: week 12, 28, 32, 40, 52, 64, 76 ]
  • The Proportion of Patients With Both Negative HBeAg and HBeAb; [ Time Frame: at week 12, 28, 32, 40, 52, 64, 76. ]
  • The Proportion of Patients With Positive Anti-HBe [ Time Frame: at week 12, 28, 32, 40, 52, 64, 76. ]
  • Change From Baseline by Vist for HBeAg Titer [ Time Frame: at week 12, 28, 32, 40, 52, 64, 76. ]
    Measuring the change in value of each visit viewpoints HBeAg titers decreased compared with baseline values

  • The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale; [ Time Frame: week 12, 28, 32, 40, 52, 64, 76 ]
  • The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml; [ Time Frame: week 12, 28, 32, 40, 52, 64, 76 ]
  • Change From Baseline by Visit for Serum HBV DNA [ Time Frame: week 12, 28, 32, 40, 52, 64, 76 ]
    Measuring the change in value of each visit viewpoints HBV DNA titers decreased compared with baseline values


Enrollment: 360
Study Start Date: June 2009
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: εPA-44 900μg
Inject εPA-44 900μg at week 0, 4, 8, 12, 20, 28.
Biological: εPA-44
Subcutaneusly injection of εPA-44 at week 0, 4, 8, 12, 20, 28.
Other Name: Therapeutic HBV vaccine
Experimental: εPA-44 600μg+Placebo 300μg
Inject εPA-44 600μg+Placebo 300μg at week 0, 4, 8, 12, 20, 28.
Biological: εPA-44
Subcutaneusly injection of εPA-44 at week 0, 4, 8, 12, 20, 28.
Other Name: Therapeutic HBV vaccine
Other: Placebo
Subcutaneusly injection of Placebo at week 0, 4, 8, 12, 20, 28.
Placebo Comparator: Placebo 900μg
Inject Placebo 900μg at week 0, 4, 8, 12, 20, 28.
Other: Placebo
Subcutaneusly injection of Placebo at week 0, 4, 8, 12, 20, 28.

Detailed Description:

First stage(0-76 weeks):

Eligible subjects are enrolled and assigned to 3 groups randomly in a 1:1:1 ratio:

  1. εPA-44 600μg group:Subcutaneous inject εPA-44 600μg at week 0, 4, 8, 12, 20, 28;Polyene Phosphatidylcholine Capsules will be taken orally beginning in week 28.
  2. εPA-44 900μg group:Subcutaneous inject εPA-44 900μg at week 0, 4, 8, 12, 20, 28;Polyene Phosphatidylcholine Capsules will be taken orally beginning in week 28.
  3. Placebo control group:Subcutaneous inject empty liposome at week 0, 4, 8, 12, 20, 28;Polyene Phosphatidylcholine Capsules will be taken orally beginning in week 28.

The study cycle consists of screening and enrollment period (week -6-0), treatment period (week 0-28) and follow-up period (week 28-76).

Second stage(76-144 weeks):

In this follow-up stage the trial is open designed, and all the subjects completed the first stage study(0-76 weeks):

  1. Subjects with no virological response and no serological response in the first stage , and refuse to continue the this follow-up study, will be provided domestic Adefovir Dipivoxil for one year freely;
  2. Subjects with virological response but no serological response/with serological response but no virological response/neither virological nor serological response in the first stage, and be willing to continue the this follow-up study, will be treated by εPA-44 900 μg;
  3. Subjects with both virological and serological response, will be followed-up to 144 weeks with no Adefovir Dipivoxil or εPA-44 900 μg treatment.

The definition of response is defined as below:

  1. Virological response: HBV DNA<2.93×10∧3IU/ml at 76 weeks;
  2. Serological response: serological conversion of HBeAg at 76 weeks.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Aged 18-65 years, male or female
  2. Conforms to diagnosis standard of chronic hepatitis B according to"2005 Guideline for Prevention and Treatment of Hepatitis B", (with positive HBsAg for more than 6 months), and HBV-DNA more than 1.0E+5 copies/ml;HBeAg (+),HBsAb(-); ALT within 2 to 10 times of ULN (upper limits of normal)
  3. HLA-A2 positive
  4. Compensatory liver disease having following hematological and biochemical indicators:WBC≥3.5E+9/L; ANC≥1.5E+9/L; PLT≥80E+9/L; Hb≥110g/L; TBil≤1.5ULN; ALB ≥ lower limit of normal value; BUN (Urea)≤upper limit of normal value; Cr≤upper limit of normal value; PT elongation≤3 sec; APTT within normal value; Fasting blood glucose≤7.0mmol/L
  5. TSH within normal value
  6. AFP ≤20ng/ml
  7. Uses effective contraception for subject with child-bearing potential (including females and female partners of males)
  8. Understands and signs ICF approved by EC
  9. Willing to comply with the study procedures and complete the study

Exclusion Criteria:

  1. Antibody of HAV IgM, HCV, HDV IgM or HEV IgM is positive
  2. Antibody of CMV IgM, EBV IgM or HIV is positive
  3. Antinuclear antibody titer>1:160
  4. Hepatocarcinoma, suspected hepatocarcinoma or hepatic cirrhosis
  5. Has any of the following illnesses or has a severe disease inappropriate for participation in the study based on the investigator's judgment, such as: Cardiovascular system: instable or significant cardiovascular illness such as angina pectoris, heart attack of myocardial infarction, congestive heart failure, severe hypertension, significant arrhythmia or abnormal ECG etc.; Respiratory system: bronchiectasis, bronchial asthma, chronic obstructive pulmonary disease, respiratory failure, etc.; Endocrine, metabolism diseases: diabetes mellitus, uncontrolled thyroid diseases, etc.; Others: autoimmune disorder, active tuberculosis, malignancies (e.g.tumor), neuropathic or metal illness history,etc.
  6. Has used anti-HBV drug (Interferon, Lamivudine, Adefovir Dipivoxil, Entecavir and Telbivudine) and immunomodulator (Thymic peptide,etc ) 6 months prior to the administration of study medication
  7. Has participated in any other drug clinical investigations within the past 3 months
  8. Has allergy habitus or has suspected allergy to study drug
  9. Female who is in pregnancy, in lactation or planning to become pregnant during the course of the study
  10. Has a history of alcohol abuse (Alcohol consumption for more than 5 years, with daily consumption over 40g for males and over 20g for females) and known drug dependence
  11. Has a history of organ transplant (except external corneal transplantation and hair transplantation)
  12. Any other factors inappropriate for enrollment in the study or study completion in the view of the investigator
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00869778

Locations
China, Beijing
The PLA Beijing Military General Hospital
BeiJing, Beijing, China
China, Heilongjiang
The 2nd Affiliated Hosptial of Harbin Medical University
Harbin, Heilongjiang, China
China, Hubei
Renmin Hosptial of Wuhan University
WuHan, Hubei, China
China, Hunan
The Second Xiangya Hospital of Central South University
Changsha, Hunan, China
The Third Xiangya Hospital of Central South University
ChangSha, Hunan, China
Xiangya Hospital Central South University
ChangSha, Hunan, China
China, Jiangsu
81th Hospital of PLA
NanJing, Jiangsu, China
China, Jilin
Jilin University First Hospital
ChangChun, Jilin, China
China, Shanxi
The First Affiliated Hospital of Xi'An JiaoTong University
Xi'An, Shanxi, China
TangDu Hospital
XiAn, Shanxi, China
China, Sichuan
West China Hospital,SiChuan University
ChengDu, Sichuan, China
China, Zhejiang
The First Affiliated Hospital of Wenzhou Medical University
WenZhou, Zhejiang, China
China
302 Militray Hosptial of China
Beijing, China
Hepatitis Institute of Peking University People's Hospital
Beijing, China
Southwest Hospital
ChongQing, China
Sponsors and Collaborators
Chongqing Jiachen Biotechnology Ltd.
Third Military Medical University
Investigators
Principal Investigator: Lai Wei, Ph.D. Hepatitis Institute of Peking University People's Hospital
  More Information

Responsible Party: Chongqing Jiachen Biotechnology Ltd.
ClinicalTrials.gov Identifier: NCT00869778     History of Changes
Other Study ID Numbers: 71006.01 
Study First Received: March 25, 2009
Results First Received: November 20, 2016
Last Updated: November 20, 2016
Individual Participant Data  
Plan to Share IPD: Undecided

Keywords provided by Chongqing Jiachen Biotechnology Ltd.:
Chronic Hepatitis B
HBeAg positive
Therapeutic HBV Vaccine
HBV-specific Cytotoxic T Lymphocyte

Additional relevant MeSH terms:
Hepatitis B
Hepatitis B, Chronic
Hepatitis
Hepatitis A
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Vaccines
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 20, 2017