Chronic Hepatitis B
Conditions
Keywords
Therapeutic HBV Vaccine, Chronic Hepatitis B, HBeAg positive, HBV-specific Cytotoxic T Lymphocyte
Brief summary
The purpose is to evaluate efficacy and safety of therapeutic hepatitis B virus (HBV) vaccine (mimogen-based)) Joint entecavir treatment in chronic hepatitis B patients.
Detailed description
Eligible subjects are enrolled and assigned into 2 groups randomly with a 1:1 ratio： 1. Therapeutic HBV vaccine Joint Entecavir group：Inject εPA-44 900μg at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48 + Oral intake entecavir 0.5mg per day ； 2. Empty liposome Joint Entecavir group：Inject empty liposome at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48 + Oral intake entecavir 0.5mg per day. The study cycle consists of screening and enrollment period (week -4～0), treatment and follow-up period (week 0-96).
Interventions
BIOLOGICALTherapeutic HBV vaccine
Inject εPA-44 900μg at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48.
DRUGentecavir
0.5mg,per day,oral intake.
OTHERplacebo
Inject placebo 900μg at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48.
Sponsors
Third Military Medical University
Chongqing Jiachen Biotechnology Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Aged 18-65 years, male or female; 2. Conforming 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), never have systemic treatment of anti-HBV viral ,and * HBV-DNA ≥ 1.72×10\^4 IU/ml； * HBeAg (+), HBeAb (-)； * 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 parameters: * WBC ≥ 3.5×10\^9/L; * ANC ≥ 1.5×10\^9/L; * PLT ≥ 80×10\^9/L; * Hb ≥ 100g/L; * TBil ≤ 1.5 ULN; * ALB not lower than low limit of normal value; * BUN no more than high limit of normal value; * Cr ≤ 1.5 ULN high limit of normal value; * PT elongation ≤ 3 sec, APTT in normal value; * Fasting blood glucose ≤ 7.0mmol/L; 5. TSH in normal value; 6. AFP test result no more than high limit of normal value; 7. Take effective contraception for subject with child-bearing potential (including females and female partners of males); 8. Understand and sign ICF approved by EC; 9. Willing to comply with the study procedures and complete the study.
Exclusion criteria
1. Antibodies of HCV, HDV or HIV is positive; 2. ANA titer \> 1:100; 3. Decompensated liver disease (such as gullet and pylorus varicose veins, hepatic encephalopathy); 4. Have the following illness or with severe disease inappropriate to participate in the study in the view of the investigator, in 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: bronchiectasia, 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, metal, acute or chronic pancreatitis illness history, etc. 5. Have used anti-HBV drug ( Interferon, Lamivudine, Adefovir Dipivoxil, Entecavir and Telbivudine ) and immunomodulator ( Thymic peptide, etc ) to the administration of study medication; 6. Have allergic diathesis or have suspected allergy to εPA-44; 7. Female in pregnancy, lactation or those who plan to pregnancy during the course of the study; 8. Have 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; 9. Have history of organ transplantation (except corneal transplantation and hair transplantation); 10. Have participated in any other drug clinical investigations within 3 months; 11. Any other factors inappropriate for enroll in the study or study completion in the view of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HBeAg Seroconversion at Week 48 | 48 weeks | Primary endpoint data were summarised under End of Study,using the last available post-baseline observation(Last Observation Carried Forward,LOCF) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serological Response | 96 weeks | Serological response at every observation time: serological conversion rate of HBeAg, negative conversion rate of HBeAg, and change of HBeAg. |
| Virological Response | 96 weeks | Virological response at every observation time: the proportion of patients with serum HBV DNA level reduction to undetectable level, decreased amount of serum HBV DNA compared with the baseline value, and HBV DNA load decrease 2 log scales or HBV DNA level \<1.72×104 IU/ml. |
| Biochemistry Response | 96 weeks | Biochemistry response at every observation time, mean the ALT level reduce to normal. |
| Histological Response | 72 weeks | Histological response at week 72, mean histological score limited reduce 2 (reduced score 2-5), and no fiber deterioration compare with before treatment. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Therapeutic HBV Vaccine+Entecavir Inject εPA-44 900μg at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48 and Oral intake entecavir 0.5mg per day.
Therapeutic HBV vaccine: Inject εPA-44 900μg at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48.
entecavir: 0.5mg,per day,oral intake. | 189 |
| Placebo+Entecavir Placebo comparator: Inject placebo 900μg at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48 and Oral intake entecavir 0.5mg per day.
entecavir: 0.5mg,per day,oral intake.
placebo: Inject placebo 900μg at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48. | 188 |
| Total | 377 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 8 | 7 |
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Protocol Violation | 3 | 4 |
| Overall Study | Withdrawal by Subject | 5 | 1 |
Baseline characteristics
| Characteristic | Therapeutic HBV Vaccine+Entecavir | Placebo+Entecavir | Total |
|---|---|---|---|
| Age, Continuous | 29.2 years STANDARD_DEVIATION 9.52 | 28.3 years STANDARD_DEVIATION 7.91 | 28.7 years STANDARD_DEVIATION 8.75 |
| BMI | 21.61 kg/m^2 STANDARD_DEVIATION 2.707 | 21.78 kg/m^2 STANDARD_DEVIATION 3.014 | 21.7 kg/m^2 STANDARD_DEVIATION 2.861 |
| Sex: Female, Male Female | 41 Participants | 46 Participants | 87 Participants |
| Sex: Female, Male Male | 148 Participants | 142 Participants | 290 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 189 | 0 / 189 |
| other Total, other adverse events | 38 / 189 | 54 / 189 |
| serious Total, serious adverse events | 1 / 189 | 0 / 189 |
Outcome results
Primary
Percentage of Participants With HBeAg Seroconversion at Week 48
Primary endpoint data were summarised under End of Study,using the last available post-baseline observation(Last Observation Carried Forward,LOCF)
Time frame: 48 weeks
Population: Intention-To-Treat Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Therapeutic HBV Vaccine+Entecavir | Percentage of Participants With HBeAg Seroconversion at Week 48 | 21 Participants |
| Placebo+Entecavir | Percentage of Participants With HBeAg Seroconversion at Week 48 | 23 Participants |
Secondary
Biochemistry Response
Biochemistry response at every observation time, mean the ALT level reduce to normal.
Time frame: 96 weeks
Secondary
Histological Response
Histological response at week 72, mean histological score limited reduce 2 (reduced score 2-5), and no fiber deterioration compare with before treatment.
Time frame: 72 weeks
Secondary
Serological Response
Serological response at every observation time: serological conversion rate of HBeAg, negative conversion rate of HBeAg, and change of HBeAg.
Time frame: 96 weeks
Secondary
Virological Response
Virological response at every observation time: the proportion of patients with serum HBV DNA level reduction to undetectable level, decreased amount of serum HBV DNA compared with the baseline value, and HBV DNA load decrease 2 log scales or HBV DNA level \<1.72×104 IU/ml.
Time frame: 96 weeks