Clinical trial NCT00869778: 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
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis B
Keywords: Chronic Hepatitis B
HBeAg positive
Therapeutic HBV Vaccine
HBV-specific Cytotoxic T Lymphocyte
Lead sponsor: Chongqing Jiachen Biotechnology Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Third Military Medical University
First posted: 2009-03-26
Enrollment: 360
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: 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：

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 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 100000 copies/ml;HBeAg (+),HBsAb(-); Alanine aminotransferase（ALT） within 2 to 10 times of ULN (upper limit 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; prothrombin time(PT) elongation≤3 sec; Activated partial thromboplastin time（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

Primary outcomes:
measure: Percentage of Participants With HBeAg Seroconversion at Endpoint .
timeFrame: Endpoint(LOCF), up to 76 Weeks
Secondary outcomes:
measure: Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76
timeFrame: serology response at week 12, 28, 32, 40, 52, 64, 76
measure: The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;
timeFrame: week 12, 28, 32, 40, 52, 64, 76
measure: Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76
timeFrame: week 12, 28, 32, 40, 52, 64, 76
measure: The Proportion of Patients With Both Negative HBeAg and HBeAb;
timeFrame: at week 12, 28, 32, 40, 52, 64, 76.
measure: The Proportion of Patients With Positive Anti-HBe
timeFrame: at week 12, 28, 32, 40, 52, 64, 76.
measure: Change From Baseline by Visit for HBeAg Titer
timeFrame: at week 12, 28, 32, 40, 52, 64, 76.
measure: The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;
timeFrame: week 12, 28, 32, 40, 52, 64, 76
measure: The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;
timeFrame: week 12, 28, 32, 40, 52, 64, 76
measure: Change From Baseline by Visit for Serum HBV DNA
timeFrame: week 12, 28, 32, 40, 52, 64, 76
Other outcomes:
Locations:
city: BeiJing
country: China
facility: The PLA Beijing Military General Hospital
state: Beijing
city: Harbin
country: China
facility: The 2nd Affiliated Hosptial of Harbin Medical University
state: Heilongjiang
city: WuHan
country: China
facility: Renmin Hosptial of Wuhan University
state: Hubei
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: ChangSha
country: China
facility: The Third Xiangya Hospital of Central South University
state: Hunan
city: ChangSha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: NanJing
country: China
facility: 81th Hospital of PLA
state: Jiangsu
city: ChangChun
country: China
facility: Jilin University First Hospital
state: Jilin
city: Xi'An
country: China
facility: The First Affiliated Hospital of Xi'An JiaoTong University
state: Shanxi
city: XiAn
country: China
facility: TangDu Hospital
state: Shanxi
city: ChengDu
country: China
facility: West China Hospital,SiChuan University
state: Sichuan
city: WenZhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Beijing
country: China
facility: 302 Militray Hosptial of China
city: Beijing
country: China
facility: Hepatitis Institute of Peking University People's Hospital
city: ChongQing
country: China
facility: Southwest Hospital
Study officials:
affiliation: Hepatitis Institute of Peking University People's Hospital
name: Lai Wei, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
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.