Back to resultsPhase 2 Trial of Therapeutic Hepatitis B Vaccine (Mimogen-based) for Chronic Hepatitis B
Primary Purpose
Chronic Hepatitis B
Status
Completed
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
εPA-44
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis B focused on measuring Chronic Hepatitis B, HBeAg positive, Therapeutic HBV Vaccine, HBV-specific Cytotoxic T Lymphocyte
Eligibility Criteria
Inclusion Criteria:
- Aged 18-65 years, male or female
- 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 100000 copies/ml;HBeAg (+),HBsAb(-); Alanine aminotransferase（ALT） within 2 to 10 times of ULN (upper limit of normal)
- HLA-A2 positive
- 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; prothrombin time(PT) elongation≤3 sec; Activated partial thromboplastin time（APTT） within normal value; Fasting blood glucose≤7.0mmol/L
- TSH within normal value
- AFP ≤20ng/ml
- Uses effective contraception for subject with child-bearing potential (including females and female partners of males)
- Understands and signs ICF approved by EC
- Willing to comply with the study procedures and complete the study
Exclusion Criteria:
- Antibody of HAV IgM, HCV, HDV IgM or HEV IgM is positive
- Antibody of CMV IgM, EBV IgM or HIV is positive
- Antinuclear antibody titer>1:160
- Hepatocarcinoma, suspected hepatocarcinoma or hepatic cirrhosis
- 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.
- 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
- Has participated in any other drug clinical investigations within the past 3 months
- Has allergy habitus or has suspected allergy to study drug
- Female who is in pregnancy, in lactation or planning to become pregnant during the course of the study
- 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
- Has a history of organ transplant (except external corneal transplantation and hair transplantation)
- Any other factors inappropriate for enrollment in the study or study completion in the view of the investigator
Sites / Locations
- The PLA Beijing Military General Hospital
- The 2nd Affiliated Hosptial of Harbin Medical University
- Renmin Hosptial of Wuhan University
- The Second Xiangya Hospital of Central South University
- The Third Xiangya Hospital of Central South University
- Xiangya Hospital Central South University
- 81th Hospital of PLA
- Jilin University First Hospital
- The First Affiliated Hospital of Xi'An JiaoTong University
- TangDu Hospital
- West China Hospital,SiChuan University
- The First Affiliated Hospital of Wenzhou Medical University
- 302 Militray Hosptial of China
- Hepatitis Institute of Peking University People's Hospital
- Southwest Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
εPA-44 900μg
εPA-44 600μg+Placebo 300μg
Placebo 900μg
Arm Description
Inject εPA-44 900μg at week 0, 4, 8, 12, 20, 28.
Inject εPA-44 600μg+Placebo 300μg at week 0, 4, 8, 12, 20, 28.
Inject Placebo 900μg at week 0, 4, 8, 12, 20, 28.
Outcomes
Primary Outcome Measures
Percentage of Participants With HBeAg Seroconversion at 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
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;
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76
The Proportion of Patients With Both Negative HBeAg and HBeAb;
The Proportion of Patients With Positive Anti-HBe
Change From Baseline by Visit for HBeAg Titer
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;
The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;
Change From Baseline by Visit for Serum HBV DNA
Measuring the change in value of each visit viewpoints HBV DNA titers decreased compared with baseline values
Full Information
NCT ID
NCT00869778
First Posted
March 25, 2009
Last Updated
September 17, 2019
Sponsor
Chongqing Jiachen Biotechnology Ltd.
Collaborators
Third Military Medical University
1. Study Identification
Unique Protocol Identification Number
NCT00869778
Brief Title
Phase 2 Trial of Therapeutic Hepatitis B Vaccine (Mimogen-based) for Chronic Hepatitis B
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
Study Type
Interventional
2. Study Status
Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
April 2009 (Actual)
Primary Completion Date
November 2011 (Actual)
Study Completion Date
May 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Chongqing Jiachen Biotechnology Ltd.
Collaborators
Third Military Medical University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose is to evaluate efficacy and safety of therapeutic Hepatitis B Virus（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.
Detailed Description
First stage(0-76 weeks):
Eligible subjects are enrolled and assigned to 3 groups randomly in a 1:1:1 ratio：
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.
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.
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):
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;
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；
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:
Virological response: HBV DNA<2.93×10∧3IU/ml at 76 weeks;
Serological response: serological conversion of HBeAg at 76 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B
Keywords
Chronic Hepatitis B, HBeAg positive, Therapeutic HBV Vaccine, HBV-specific Cytotoxic T Lymphocyte
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
360 (Actual)
8. Arms, Groups, and Interventions
Arm Title
εPA-44 900μg
Arm Type
Experimental
Arm Description
Inject εPA-44 900μg at week 0, 4, 8, 12, 20, 28.
Arm Title
εPA-44 600μg+Placebo 300μg
Arm Type
Experimental
Arm Description
Inject εPA-44 600μg+Placebo 300μg at week 0, 4, 8, 12, 20, 28.
Arm Title
Placebo 900μg
Arm Type
Placebo Comparator
Arm Description
Inject Placebo 900μg at week 0, 4, 8, 12, 20, 28.
Intervention Type
Biological
Intervention Name(s)
εPA-44
Other Intervention Name(s)
Therapeutic HBV vaccine
Intervention Description
subcutaneously injection of εPA-44 at week 0, 4, 8, 12, 20, 28.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
subcutaneously injection of Placebo at week 0, 4, 8, 12, 20, 28.
Primary Outcome Measure Information:
Title
Percentage of Participants With HBeAg Seroconversion at Endpoint .
Description
Primary endpoint data were summarised under "End of Study",using the last available post-baseline observation(Last Observation Carried Forward,LOCF)
Time Frame
Endpoint(LOCF), up to 76 Weeks
Secondary Outcome Measure Information:
Title
Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76
Description
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
Time Frame
serology response at week 12, 28, 32, 40, 52, 64, 76
Title
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
Title
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
Title
The Proportion of Patients With Both Negative HBeAg and HBeAb;
Time Frame
at week 12, 28, 32, 40, 52, 64, 76.
Title
The Proportion of Patients With Positive Anti-HBe
Time Frame
at week 12, 28, 32, 40, 52, 64, 76.
Title
Change From Baseline by Visit for HBeAg Titer
Description
Measuring the change in value of each visit viewpoints HBeAg titers decreased compared with baseline values
Time Frame
at week 12, 28, 32, 40, 52, 64, 76.
Title
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
Title
The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;
Time Frame
week 12, 28, 32, 40, 52, 64, 76
Title
Change From Baseline by Visit for Serum HBV DNA
Description
Measuring the change in value of each visit viewpoints HBV DNA titers decreased compared with baseline values
Time Frame
week 12, 28, 32, 40, 52, 64, 76
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Aged 18-65 years, male or female
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 100000 copies/ml;HBeAg (+),HBsAb(-); Alanine aminotransferase（ALT） within 2 to 10 times of ULN (upper limit of normal)
HLA-A2 positive
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; prothrombin time(PT) elongation≤3 sec; Activated partial thromboplastin time（APTT） within normal value; Fasting blood glucose≤7.0mmol/L
TSH within normal value
AFP ≤20ng/ml
Uses effective contraception for subject with child-bearing potential (including females and female partners of males)
Understands and signs ICF approved by EC
Willing to comply with the study procedures and complete the study
Exclusion Criteria:
Antibody of HAV IgM, HCV, HDV IgM or HEV IgM is positive
Antibody of CMV IgM, EBV IgM or HIV is positive
Antinuclear antibody titer>1:160
Hepatocarcinoma, suspected hepatocarcinoma or hepatic cirrhosis
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.
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
Has participated in any other drug clinical investigations within the past 3 months
Has allergy habitus or has suspected allergy to study drug
Female who is in pregnancy, in lactation or planning to become pregnant during the course of the study
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
Has a history of organ transplant (except external corneal transplantation and hair transplantation)
Any other factors inappropriate for enrollment in the study or study completion in the view of the investigator
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lai Wei, Ph.D.
Organizational Affiliation
Hepatitis Institute of Peking University People's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
The PLA Beijing Military General Hospital
City
BeiJing
State/Province
Beijing
Country
China
Facility Name
The 2nd Affiliated Hosptial of Harbin Medical University
City
Harbin
State/Province
Heilongjiang
Country
China
Facility Name
Renmin Hosptial of Wuhan University
City
WuHan
State/Province
Hubei
Country
China
Facility Name
The Second Xiangya Hospital of Central South University
City
Changsha
State/Province
Hunan
Country
China
Facility Name
The Third Xiangya Hospital of Central South University
City
ChangSha
State/Province
Hunan
Country
China
Facility Name
Xiangya Hospital Central South University
City
ChangSha
State/Province
Hunan
Country
China
Facility Name
81th Hospital of PLA
City
NanJing
State/Province
Jiangsu
Country
China
Facility Name
Jilin University First Hospital
City
ChangChun
State/Province
Jilin
Country
China
Facility Name
The First Affiliated Hospital of Xi'An JiaoTong University
City
Xi'An
State/Province
Shanxi
Country
China
Facility Name
TangDu Hospital
City
XiAn
State/Province
Shanxi
Country
China
Facility Name
West China Hospital,SiChuan University
City
ChengDu
State/Province
Sichuan
Country
China
Facility Name
The First Affiliated Hospital of Wenzhou Medical University
City
WenZhou
State/Province
Zhejiang
Country
China
Facility Name
302 Militray Hosptial of China
City
Beijing
Country
China
Facility Name
Hepatitis Institute of Peking University People's Hospital
City
Beijing
Country
China
Facility Name
Southwest Hospital
City
ChongQing
Country
China
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
34396571
Citation
Wei L, Zhao T, Zhang J, Mao Q, Gong G, Sun Y, Chen Y, Wang M, Tan D, Gong Z, Li B, Niu J, Li S, Gong H, Zou L, Zhou W, Jia Z, Tang Y, Fei L, Hu Y, Shang X, Han J, Zhang B, Wu Y. Efficacy and safety of a nanoparticle therapeutic vaccine in patients with chronic hepatitis B: A randomized clinical trial. Hepatology. 2022 Jan;75(1):182-195. doi: 10.1002/hep.32109. Epub 2021 Dec 8.
Results Reference
derived
Learn more about this trial
Phase 2 Trial of Therapeutic Hepatitis B Vaccine (Mimogen-based) for Chronic Hepatitis B
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