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

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

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00869778

Enrollment

360

Registered

2009-03-26

Start date

2009-04-30

Completion date

2013-05-31

Last updated

2019-10-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Chronic Hepatitis B

Keywords

Chronic Hepatitis B, HBeAg positive, Therapeutic HBV Vaccine, HBV-specific Cytotoxic T Lymphocyte

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.

Interventions

BIOLOGICALεPA-44

subcutaneously injection of εPA-44 at week 0, 4, 8, 12, 20, 28.

OTHERPlacebo

subcutaneously injection of Placebo at week 0, 4, 8, 12, 20, 28.

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

Inclusion criteria

1. Aged 18-65 years, male or female 2. Conforms to diagnosis standard of chronic hepatitis B according to2005 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

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants With HBeAg Seroconversion at Endpoint .	Endpoint(LOCF), up to 76 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
The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;	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	week 12, 28, 32, 40, 52, 64, 76	—
The Proportion of Patients With Both Negative HBeAg and HBeAb;	at week 12, 28, 32, 40, 52, 64, 76.	—
The Proportion of Patients With Positive Anti-HBe	at week 12, 28, 32, 40, 52, 64, 76.	—
Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76	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 2 Log Scale;	week 12, 28, 32, 40, 52, 64, 76	—
The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;	week 12, 28, 32, 40, 52, 64, 76	—
Change From Baseline by Visit for Serum HBV DNA	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
Change From Baseline by Visit for HBeAg Titer	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

Countries

China

Participant flow

Recruitment details

Participants were enrolled at 15 sites in the China. The first participant was screened on 26 March 2009. The last participant observation for the Week 76 analysis was on 09 October 2011

Pre-assignment details

1218 participants were screened and 360 were randomized; 360 randomized participants received at least one dose of study drug, and comprise the Safety Analysis Set and the Full Analysis Set.

Participants by arm

Arm	Count
εPA-44 900μg Inject εPA-44 900μg at week 0, 4, 8, 12, 20, 28. εPA-44: Inject εPA-44 900μg/600μg at week 0, 4, 8, 12, 20, 28.	120
εPA-44 600μg+Placebo 300μg Inject εPA-44 600μg+Placebo 300μg at week 0, 4, 8, 12, 20, 28. εPA-44: Inject εPA-44 900μg/600μg at week 0, 4, 8, 12, 20, 28. Placebo: Inject Placebo 900μg at week 0, 4, 8, 12, 20, 28.	120
Placebo 900μg Inject Placebo 900μg at week 0, 4, 8, 12, 20, 28. Placebo: Inject Placebo 900μg at week 0, 4, 8, 12, 20, 28.	120
Total	360

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	2	0	0
Overall Study	Pregnancy	1	0	0
Overall Study	Protocol Violation	5	3	5
Overall Study	Unblinding	1	0	0
Overall Study	Withdrawal by Subject	3	4	5

Baseline characteristics

Characteristic	Placebo 900μg	Total	εPA-44 900μg	εPA-44 600μg+Placebo 300μg
Age, Continuous	27.4 years STANDARD_DEVIATION 7.3	26.8 years STANDARD_DEVIATION 7.93	26.7 years STANDARD_DEVIATION 7.28	26.9 years STANDARD_DEVIATION 8.56
Body Mass Index (BMI)	21.99 kg/m^2 STANDARD_DEVIATION 2.643	21.74 kg/m^2 STANDARD_DEVIATION 2.998	21.92 kg/m^2 STANDARD_DEVIATION 2.992	21.55 kg/m^2 STANDARD_DEVIATION 3.004
Sex: Female, Male Female	33 Participants	95 Participants	36 Participants	26 Participants
Sex: Female, Male Male	87 Participants	265 Participants	84 Participants	94 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	56 / 120	66 / 120	52 / 120
serious Total, serious adverse events	3 / 120	2 / 120	1 / 120

Outcome results

Primary

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)

Time frame: Endpoint(LOCF), up to 76 Weeks

Population: Intention-To-Treat Population

Arm	Measure	Value (NUMBER)
εPA-44 900μg	Percentage of Participants With HBeAg Seroconversion at Endpoint .	38.8 percentage of participants
εPA-44 600μg+Placebo 300μg	Percentage of Participants With HBeAg Seroconversion at Endpoint .	28.6 percentage of participants
Placebo 900μg	Percentage of Participants With HBeAg Seroconversion at Endpoint .	20.2 percentage of participants

Secondary

Change From Baseline by Visit for HBeAg Titer

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.

Population: Intent-to-treat population

Arm	Measure	Group	Value (MEAN)	Dispersion
εPA-44 900μg	Change From Baseline by Visit for HBeAg Titer	Week 28	-285.4 IU/mL	Standard Deviation 1343.17
εPA-44 900μg	Change From Baseline by Visit for HBeAg Titer	Week 76	-327.5 IU/mL	Standard Deviation 1286.44
εPA-44 900μg	Change From Baseline by Visit for HBeAg Titer	Week 40	-407.4 IU/mL	Standard Deviation 1523.68
εPA-44 900μg	Change From Baseline by Visit for HBeAg Titer	Week 64	-271.8 IU/mL	Standard Deviation 1267.02
εPA-44 900μg	Change From Baseline by Visit for HBeAg Titer	Week 12	11.5 IU/mL	Standard Deviation 1250.38
εPA-44 900μg	Change From Baseline by Visit for HBeAg Titer	Week 52	-410.0 IU/mL	Standard Deviation 1637.26
εPA-44 900μg	Change From Baseline by Visit for HBeAg Titer	Week 32	-339.3 IU/mL	Standard Deviation 1442.08
εPA-44 600μg+Placebo 300μg	Change From Baseline by Visit for HBeAg Titer	Week 52	-788.0 IU/mL	Standard Deviation 3015.94
εPA-44 600μg+Placebo 300μg	Change From Baseline by Visit for HBeAg Titer	Week 64	-822.8 IU/mL	Standard Deviation 3124.94
εPA-44 600μg+Placebo 300μg	Change From Baseline by Visit for HBeAg Titer	Week 76	-947.4 IU/mL	Standard Deviation 3231.94
εPA-44 600μg+Placebo 300μg	Change From Baseline by Visit for HBeAg Titer	Week 32	-768.3 IU/mL	Standard Deviation 2778.79
εPA-44 600μg+Placebo 300μg	Change From Baseline by Visit for HBeAg Titer	Week 28	-725.2 IU/mL	Standard Deviation 2774.22
εPA-44 600μg+Placebo 300μg	Change From Baseline by Visit for HBeAg Titer	Week 40	-737.6 IU/mL	Standard Deviation 2944.83
εPA-44 600μg+Placebo 300μg	Change From Baseline by Visit for HBeAg Titer	Week 12	-460.2 IU/mL	Standard Deviation 2650.77
Placebo 900μg	Change From Baseline by Visit for HBeAg Titer	Week 76	-629.3 IU/mL	Standard Deviation 1846.07
Placebo 900μg	Change From Baseline by Visit for HBeAg Titer	Week 28	-450.3 IU/mL	Standard Deviation 1673.79
Placebo 900μg	Change From Baseline by Visit for HBeAg Titer	Week 32	-471.3 IU/mL	Standard Deviation 1692.48
Placebo 900μg	Change From Baseline by Visit for HBeAg Titer	Week 40	-496.8 IU/mL	Standard Deviation 1721.17
Placebo 900μg	Change From Baseline by Visit for HBeAg Titer	Week 52	-458.9 IU/mL	Standard Deviation 1791.04
Placebo 900μg	Change From Baseline by Visit for HBeAg Titer	Week 64	-563.4 IU/mL	Standard Deviation 1800.32
Placebo 900μg	Change From Baseline by Visit for HBeAg Titer	Week 12	-278.7 IU/mL	Standard Deviation 1561.74

Secondary

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

Time frame: week 12, 28, 32, 40, 52, 64, 76

Population: Intent-to-treat population

Arm	Measure	Group	Value (MEAN)	Dispersion
εPA-44 900μg	Change From Baseline by Visit for Serum HBV DNA	Week 28	-213000000 IU/mL	Standard Deviation 919000000
εPA-44 900μg	Change From Baseline by Visit for Serum HBV DNA	Week 52	-219000000 IU/mL	Standard Deviation 917500000
εPA-44 900μg	Change From Baseline by Visit for Serum HBV DNA	Week 40	-229000000 IU/mL	Standard Deviation 917000000
εPA-44 900μg	Change From Baseline by Visit for Serum HBV DNA	Week 12	-176000000 IU/mL	Standard Deviation 927000000
εPA-44 900μg	Change From Baseline by Visit for Serum HBV DNA	Week 76	-276000000 IU/mL	Standard Deviation 870500000
εPA-44 900μg	Change From Baseline by Visit for Serum HBV DNA	Week 64	-229000000 IU/mL	Standard Deviation 932100000
εPA-44 900μg	Change From Baseline by Visit for Serum HBV DNA	Week 32	-226000000 IU/mL	Standard Deviation 925700000
εPA-44 600μg+Placebo 300μg	Change From Baseline by Visit for Serum HBV DNA	Week 40	-387000000 IU/mL	Standard Deviation 1236000000
εPA-44 600μg+Placebo 300μg	Change From Baseline by Visit for Serum HBV DNA	Week 12	-336000000 IU/mL	Standard Deviation 1195000000
εPA-44 600μg+Placebo 300μg	Change From Baseline by Visit for Serum HBV DNA	Week 28	-362000000 IU/mL	Standard Deviation 1217000000
εPA-44 600μg+Placebo 300μg	Change From Baseline by Visit for Serum HBV DNA	Week 32	-372000000 IU/mL	Standard Deviation 1218000000
εPA-44 600μg+Placebo 300μg	Change From Baseline by Visit for Serum HBV DNA	Week 52	-373000000 IU/mL	Standard Deviation 1263000000
εPA-44 600μg+Placebo 300μg	Change From Baseline by Visit for Serum HBV DNA	Week 64	-362000000 IU/mL	Standard Deviation 1045000000
εPA-44 600μg+Placebo 300μg	Change From Baseline by Visit for Serum HBV DNA	Week 76	-408000000 IU/mL	Standard Deviation 1303000000
Placebo 900μg	Change From Baseline by Visit for Serum HBV DNA	Week 52	-140000000 IU/mL	Standard Deviation 311600000
Placebo 900μg	Change From Baseline by Visit for Serum HBV DNA	Week 28	-172000000 IU/mL	Standard Deviation 299000000
Placebo 900μg	Change From Baseline by Visit for Serum HBV DNA	Week 76	-207000000 IU/mL	Standard Deviation 350200000
Placebo 900μg	Change From Baseline by Visit for Serum HBV DNA	Week 64	-168000000 IU/mL	Standard Deviation 340500000
Placebo 900μg	Change From Baseline by Visit for Serum HBV DNA	Week 40	-181000000 IU/mL	Standard Deviation 322700000
Placebo 900μg	Change From Baseline by Visit for Serum HBV DNA	Week 32	-172000000 IU/mL	Standard Deviation 308500000
Placebo 900μg	Change From Baseline by Visit for Serum HBV DNA	Week 12	-129000000 IU/mL	Standard Deviation 293200000

Secondary

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

Population: Intent-to-treat population

Arm	Measure	Group	Value (NUMBER)
εPA-44 900μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 28	32.8 percentage of participants
εPA-44 900μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 76	48.3 percentage of participants
εPA-44 900μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 40	39.7 percentage of participants
εPA-44 900μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 32	32.8 percentage of participants
εPA-44 900μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 4	9.5 percentage of participants
εPA-44 900μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 64	44 percentage of participants
εPA-44 900μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 12	19 percentage of participants
εPA-44 900μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 8	12.9 percentage of participants
εPA-44 900μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 52	36.2 percentage of participants
εPA-44 600μg+Placebo 300μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 32	29.4 percentage of participants
εPA-44 600μg+Placebo 300μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 4	4.2 percentage of participants
εPA-44 600μg+Placebo 300μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 8	8.4 percentage of participants
εPA-44 600μg+Placebo 300μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 12	10.9 percentage of participants
εPA-44 600μg+Placebo 300μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 28	20.2 percentage of participants
εPA-44 600μg+Placebo 300μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 40	31.9 percentage of participants
εPA-44 600μg+Placebo 300μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 52	33.6 percentage of participants
εPA-44 600μg+Placebo 300μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 64	38.7 percentage of participants
εPA-44 600μg+Placebo 300μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 76	37.8 percentage of participants
Placebo 900μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 12	13.4 percentage of participants
Placebo 900μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 4	6.7 percentage of participants
Placebo 900μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 52	21.8 percentage of participants
Placebo 900μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 8	11.8 percentage of participants
Placebo 900μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 76	34.5 percentage of participants
Placebo 900μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 32	18.5 percentage of participants
Placebo 900μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 28	20.2 percentage of participants
Placebo 900μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 64	26.9 percentage of participants
Placebo 900μg	Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76	Week 40	26.9 percentage of participants

Secondary

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

Time frame: serology response at week 12, 28, 32, 40, 52, 64, 76

Population: Intent-to-treat population

Arm	Measure	Group	Value (NUMBER)
εPA-44 900μg	Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76	Week 28	13.8 percentage of participants
εPA-44 900μg	Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76	Week 52	25.9 percentage of participants
εPA-44 900μg	Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76	Week 40	22.4 percentage of participants
εPA-44 900μg	Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76	Week 12	8.6 percentage of participants
εPA-44 900μg	Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76	Week 76	37.9 percentage of participants
εPA-44 900μg	Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76	Week 64	31.9 percentage of participants
εPA-44 900μg	Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76	Week 32	16.4 percentage of participants
εPA-44 600μg+Placebo 300μg	Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76	Week 40	20.2 percentage of participants
εPA-44 600μg+Placebo 300μg	Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76	Week 12	7.6 percentage of participants
εPA-44 600μg+Placebo 300μg	Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76	Week 28	12.6 percentage of participants
εPA-44 600μg+Placebo 300μg	Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76	Week 32	13.4 percentage of participants
εPA-44 600μg+Placebo 300μg	Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76	Week 52	22.7 percentage of participants
εPA-44 600μg+Placebo 300μg	Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76	Week 64	24.4 percentage of participants
εPA-44 600μg+Placebo 300μg	Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76	Week 76	28.6 percentage of participants
Placebo 900μg	Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76	Week 52	10.9 percentage of participants
Placebo 900μg	Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76	Week 28	7.6 percentage of participants
Placebo 900μg	Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76	Week 76	18.5 percentage of participants
Placebo 900μg	Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76	Week 64	14.3 percentage of participants
Placebo 900μg	Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76	Week 40	10.9 percentage of participants
Placebo 900μg	Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76	Week 32	9.2 percentage of participants
Placebo 900μg	Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76	Week 12	1.7 percentage of participants

Secondary

The Proportion of Patients With Both Negative HBeAg and HBeAb;

Time frame: at week 12, 28, 32, 40, 52, 64, 76.

Population: Intent-to-treat population

Arm	Measure	Group	Value (NUMBER)
εPA-44 900μg	The Proportion of Patients With Both Negative HBeAg and HBeAb;	Week 64	0 percentage of participants
εPA-44 900μg	The Proportion of Patients With Both Negative HBeAg and HBeAb;	Week 52	0 percentage of participants
εPA-44 900μg	The Proportion of Patients With Both Negative HBeAg and HBeAb;	Week 40	0 percentage of participants
εPA-44 900μg	The Proportion of Patients With Both Negative HBeAg and HBeAb;	Week 12	0 percentage of participants
εPA-44 900μg	The Proportion of Patients With Both Negative HBeAg and HBeAb;	Week 32	0 percentage of participants
εPA-44 900μg	The Proportion of Patients With Both Negative HBeAg and HBeAb;	Week 28	0 percentage of participants
εPA-44 900μg	The Proportion of Patients With Both Negative HBeAg and HBeAb;	Week 76	0.9 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Both Negative HBeAg and HBeAb;	Week 40	0 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Both Negative HBeAg and HBeAb;	Week 28	0 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Both Negative HBeAg and HBeAb;	Week 32	0 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Both Negative HBeAg and HBeAb;	Week 12	0 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Both Negative HBeAg and HBeAb;	Week 52	0 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Both Negative HBeAg and HBeAb;	Week 64	0 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Both Negative HBeAg and HBeAb;	Week 76	0.8 percentage of participants
Placebo 900μg	The Proportion of Patients With Both Negative HBeAg and HBeAb;	Week 52	0 percentage of participants
Placebo 900μg	The Proportion of Patients With Both Negative HBeAg and HBeAb;	Week 12	0 percentage of participants
Placebo 900μg	The Proportion of Patients With Both Negative HBeAg and HBeAb;	Week 76	0 percentage of participants
Placebo 900μg	The Proportion of Patients With Both Negative HBeAg and HBeAb;	Week 64	0 percentage of participants
Placebo 900μg	The Proportion of Patients With Both Negative HBeAg and HBeAb;	Week 40	0 percentage of participants
Placebo 900μg	The Proportion of Patients With Both Negative HBeAg and HBeAb;	Week 32	0 percentage of participants
Placebo 900μg	The Proportion of Patients With Both Negative HBeAg and HBeAb;	Week 28	0 percentage of participants

Secondary

The Proportion of Patients With Positive Anti-HBe

Time frame: at week 12, 28, 32, 40, 52, 64, 76.

Population: Intent-to-treat population

Arm	Measure	Group	Value (NUMBER)
εPA-44 900μg	The Proportion of Patients With Positive Anti-HBe	Week 52	31.0 percentage of participants
εPA-44 900μg	The Proportion of Patients With Positive Anti-HBe	Week 28	25.9 percentage of participants
εPA-44 900μg	The Proportion of Patients With Positive Anti-HBe	Week 64	36.2 percentage of participants
εPA-44 900μg	The Proportion of Patients With Positive Anti-HBe	Week 76	44.0 percentage of participants
εPA-44 900μg	The Proportion of Patients With Positive Anti-HBe	Week 12	15.5 percentage of participants
εPA-44 900μg	The Proportion of Patients With Positive Anti-HBe	Week 32	29.3 percentage of participants
εPA-44 900μg	The Proportion of Patients With Positive Anti-HBe	Week 40	31.0 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Positive Anti-HBe	Week 76	37.0 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Positive Anti-HBe	Week 52	34.5 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Positive Anti-HBe	Week 40	31.1 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Positive Anti-HBe	Week 32	27.7 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Positive Anti-HBe	Week 64	38.7 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Positive Anti-HBe	Week 28	26.1 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Positive Anti-HBe	Week 12	14.3 percentage of participants
Placebo 900μg	The Proportion of Patients With Positive Anti-HBe	Week 32	20.2 percentage of participants
Placebo 900μg	The Proportion of Patients With Positive Anti-HBe	Week 12	10.9 percentage of participants
Placebo 900μg	The Proportion of Patients With Positive Anti-HBe	Week 28	18.5 percentage of participants
Placebo 900μg	The Proportion of Patients With Positive Anti-HBe	Week 76	29.4 percentage of participants
Placebo 900μg	The Proportion of Patients With Positive Anti-HBe	Week 40	22.7 percentage of participants
Placebo 900μg	The Proportion of Patients With Positive Anti-HBe	Week 52	18.5 percentage of participants
Placebo 900μg	The Proportion of Patients With Positive Anti-HBe	Week 64	23.5 percentage of participants

Secondary

The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;

Time frame: week 12, 28, 32, 40, 52, 64, 76

Population: Intent-to-treat population

Arm	Measure	Group	Value (NUMBER)
εPA-44 900μg	The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;	Week 32	21.6 percentage of participants
εPA-44 900μg	The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;	Week 76	42.2 percentage of participants
εPA-44 900μg	The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;	Week 52	29.3 percentage of participants
εPA-44 900μg	The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;	Week 40	23.3 percentage of participants
εPA-44 900μg	The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;	Week 28	17.2 percentage of participants
εPA-44 900μg	The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;	Week 12	7.8 percentage of participants
εPA-44 900μg	The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;	Week 64	30.2 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;	Week 76	32.8 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;	Week 12	10.9 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;	Week 28	17.6 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;	Week 32	20.2 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;	Week 40	24.4 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;	Week 52	26.9 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;	Week 64	31.1 percentage of participants
Placebo 900μg	The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;	Week 12	5.9 percentage of participants
Placebo 900μg	The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;	Week 52	11.8 percentage of participants
Placebo 900μg	The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;	Week 28	11.8 percentage of participants
Placebo 900μg	The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;	Week 76	27.7 percentage of participants
Placebo 900μg	The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;	Week 64	19.3 percentage of participants
Placebo 900μg	The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;	Week 40	12.6 percentage of participants
Placebo 900μg	The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;	Week 32	10.1 percentage of participants

Secondary

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

Population: Intent-to-treat population

Arm	Measure	Group	Value (NUMBER)
εPA-44 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;	Week 12	29.3 percentage of participants
εPA-44 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;	Week 40	49.1 percentage of participants
εPA-44 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;	Week 32	50.0 percentage of participants
εPA-44 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;	Week 76	62.1 percentage of participants
εPA-44 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;	Week 64	54.3 percentage of participants
εPA-44 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;	Week 52	48.3 percentage of participants
εPA-44 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;	Week 28	42.2 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;	Week 32	55.5 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;	Week 76	64.7 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;	Week 12	33.6 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;	Week 28	48.7 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;	Week 40	55.5 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;	Week 52	53.8 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;	Week 64	61.3 percentage of participants
Placebo 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;	Week 40	47.9 percentage of participants
Placebo 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;	Week 12	27.7 percentage of participants
Placebo 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;	Week 64	43.7 percentage of participants
Placebo 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;	Week 52	36.1 percentage of participants
Placebo 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;	Week 32	45.4 percentage of participants
Placebo 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;	Week 28	39.5 percentage of participants
Placebo 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;	Week 76	55.5 percentage of participants

Secondary

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

Population: Intent-to-treat population

Arm	Measure	Group	Value (NUMBER)
εPA-44 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;	Week 28	29.3 percentage of participants
εPA-44 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;	Week 52	37.9 percentage of participants
εPA-44 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;	Week 40	35.3 percentage of participants
εPA-44 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;	Week 12	12.9 percentage of participants
εPA-44 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;	Week 76	50.0 percentage of participants
εPA-44 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;	Week 64	41.4 percentage of participants
εPA-44 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;	Week 32	28.4 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;	Week 40	40.3 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;	Week 12	19.3 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;	Week 28	31.1 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;	Week 32	33.6 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;	Week 52	42.9 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;	Week 64	47.9 percentage of participants
εPA-44 600μg+Placebo 300μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;	Week 76	48.7 percentage of participants
Placebo 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;	Week 52	23.5 percentage of participants
Placebo 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;	Week 28	24.4 percentage of participants
Placebo 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;	Week 76	40.3 percentage of participants
Placebo 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;	Week 64	31.1 percentage of participants
Placebo 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;	Week 40	26.1 percentage of participants
Placebo 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;	Week 32	24.4 percentage of participants
Placebo 900μg	The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;	Week 12	13.4 percentage of participants

Source: ClinicalTrials.gov · Data processed: Feb 14, 2026

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

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Percentage of Participants With HBeAg Seroconversion at Endpoint .

Change From Baseline by Visit for HBeAg Titer

Change From Baseline by Visit for Serum HBV DNA

Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76

Percentage of Participants With HBeAg Seroconversion 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

The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;

The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;

The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;