Therapeutic Hepatitis B Vaccine (Synthesized Peptide) in Treating Chronic Hepatitis B Patients

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2012 by Chongqing Jiachen Biotechnology Ltd..
Recruitment status was  Active, not recruiting
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: June 14, 2012
Last verified: June 2012
  Purpose

The purpose is to evaluate efficacy and safety of therapeutic HBV vaccine (synthesized peptide) 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: The therapeutic (synthesized peptide) HBV vaccine (εPA-44)
Biological: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
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 (Synthesized Peptide) in Treating Chronic Hepatitis B Patients

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Primary efficacy assessment is the proportion of patients about HBeAg / anti-HBe seroconversion at the end of the follow-up period. [ Time Frame: week 76, week 144 ] [ Designated as safety issue: Yes ]
    First stage: the primary assessment is at week 76, and in second stage is at week 144.


Secondary Outcome Measures:
  • Secondary efficacy parameters include serology response at week 12, 28, 32, 40, 52, 64,76, 95,108, 120, 144. [ Time Frame: week 12, 28, 32, 40, 52, 64, 76, 95,108, 120, 144 ] [ Designated as safety issue: Yes ]
    1. The proportion of patients about HBeAg / anti-HBe Serological conversion;
    2. The proportion of patients that HBeAg is negative, but anti-HBe is still negative;
    3. The proportion of patients that anti-HBe is positive;
    4. Change of HBeAg titer.

  • Virological response at each observation time point at week 12, 28, 32, 40, 52, 64, 76. [ Time Frame: week 12, 28, 32, 40, 52, 64, 76 ] [ Designated as safety issue: Yes ]
    1. The proportion of patients with serum HBV DNA load decrease epual or greater than 1 log scale;
    2. The proportion of patients with serum HBV DNA load decrease epual or greater than 2 log scales;
    3. The proportion of patients with serum HBV DNA level < 2.93 × 104 IU / ml;
    4. Decreased amount of serum HBV DNA compared with the baseline value.

  • Biochemistry response at every observation point. [ Time Frame: week 12, 28, 32, 40, 52, 64, 76 ] [ Designated as safety issue: Yes ]
    1. The proportion of patients with ALT reyurned to normal;
    2. The chang of ALT at every observation point.

  • Virological response at each observation time point at week 95, 108, 120, 144. [ Time Frame: Week 95, 108, 120, 144 ] [ Designated as safety issue: Yes ]
    1. The proportion of patients with serum HBV DNA level unable to be detected or lower than limit;
    2. Decreased amount of serum HBV DNA compared with the baseline value;
    3. The proportion of patients with serum HBV DNA decrease equal or greater 2 log scales or level < 2.93 × 104 IU / ml.


Enrollment: 360
Study Start Date: June 2009
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: εPA-44 900μg Biological: The therapeutic (synthesized peptide) HBV vaccine (εPA-44)
The therapeutic (synthesized peptide) HBV vaccine (εPA-44)
Other Name: εPA-44
Experimental: εPA-44 600μg Biological: The therapeutic (synthesized peptide) HBV vaccine (εPA-44)
The therapeutic (synthesized peptide) HBV vaccine (εPA-44)
Other Name: εPA-44
Placebo Comparator: Placebo Biological: Placebo
Placebo
Other Name: Placebo

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):

According to this follow-up stage, open designed, the subjects completed the first stage study(0-76 weeks):

  1. If no virological response and no serological response, and refuse to continue the follow-up study, will be provided domestic Adefovir Dipivoxil for one year freely;
  2. If have virological response but no serological response/have serological response but no virological response/neither virological nor serological response, and be willing to continue the follow-up study, will be treated by εPA-44 900 μg;
  3. If have both virological and serological response, will be observed to 144 weeks.

The definition of response as below:

  1. Virological response: HBV DNA<2.93×103IU/ml at 76 weeks;
  2. Serological response: HBeAg appears to serological conversion at 76 weeks.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
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 (Thymopeptides, 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
Hepatitis Institute of Peking University People's Hospital
Beijing, China
Sponsors and Collaborators
Chongqing Jiachen Biotechnology Ltd.
Third Military Medical University
  More Information

No publications provided

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
Last Updated: June 14, 2012
Health Authority: China: Food and Drug Administration

Keywords provided by Chongqing Jiachen Biotechnology Ltd.:
HBeAg positive Chronic Hepatitis B

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

ClinicalTrials.gov processed this record on July 26, 2014