A Clinical Study on Therapeutic Double-plasmid Hepatitis B Virus (HBV) DNA Vaccine in Patients With HBeAg-positive Chronic Hepatitis B

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2009 by The 458 Hospital of Chinese PLA.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
Guangzhou Baidi Biotechnology Co., Ltd
Guangzhou Pharmaceucal Company Limited
Information provided by:
The 458 Hospital of Chinese PLA
ClinicalTrials.gov Identifier:
NCT01189656
First received: August 25, 2010
Last updated: August 26, 2010
Last verified: February 2009
  Purpose

To preliminarily evaluate the efficiency and safety of therapeutic double- plasmid HBV DNA vaccine on HBeAg-positive, chronic hepatitis B patients, and provide evidence for the next dosing regimen.


Condition Intervention Phase
Chronic Hepatitis B Patients With HBeAg-positive
Biological: HBV DNA Vaccine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Study on Specific-Population to Evaluate the Safety and Efficacy of Therapeutic Double-plasmid HBV DNA Vaccine in HBeAg-positive Patients With Chronic Hepatitis B

Resource links provided by NLM:


Further study details as provided by The 458 Hospital of Chinese PLA:

Primary Outcome Measures:
  • The change of HBV DNA load at Week 72 [ Time Frame: 72 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The rate of subjects with HBV DNA titer reducing > 2 logarithms . [ Time Frame: Every 12 weeks ] [ Designated as safety issue: Yes ]
  • The change of HBeAg and HBsAg titer. [ Time Frame: Every 12 weeks ] [ Designated as safety issue: Yes ]
  • The change of ALT. [ Time Frame: Every 12 weeks ] [ Designated as safety issue: Yes ]
  • HBsAg/HBeAg serum conversion rate. [ Time Frame: Every 12 weeks ] [ Designated as safety issue: Yes ]
  • The INF-gamma expression level in peripheral blood mononuclear cells (PBMC). [ Time Frame: Every 12 weeks ] [ Designated as safety issue: Yes ]
  • The amount of HBV-specific CTL. [ Time Frame: Every 12 weeks ] [ Designated as safety issue: Yes ]
  • The change of expression level of peripheral cytokines (IL-4、IL-10、IL-12 and INF-gamma) against the baseline level. [ Time Frame: Every 12 weeks ] [ Designated as safety issue: Yes ]
  • The different occurence rates of HBV Drug Resistance Gene (YMDD) between the 2 arms. [ Time Frame: 72 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 33
Study Start Date: January 2009
Estimated Study Completion Date: December 2010
Estimated Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Vaccine+Lamivudine group
Subjects assigned into the experimental and the controlled groups with randomization and double-blindness by a ratio of 2:1
Biological: HBV DNA Vaccine
HBV DNA Vaccine, 1mg/ml/syringe, formulation
Other Name: Therapeutic Double-plasmid HBV DNA Vaccine
Placebo Comparator: Placebo+Lamivudine group Biological: HBV DNA Vaccine
HBV DNA Vaccine, 1mg/ml/syringe, formulation
Other Name: Therapeutic Double-plasmid HBV DNA Vaccine

Detailed Description:

The current study is a multicenter, randomized, double-blind, placebo- controlled clinical trial. The eligible subjects are assigned randomly into 2 arms, the Vaccine + Lamivudine group and the Placebo + Lamivudine group, respectively, by a ratio of 2:1. The efficacy variables include the change of HBV DNA load at Week 72, and at each visits the rate of subjects with HBV DNA titer reducing > 2 logarithms ,the change of HBeAg and HBsAg titer, the change of ALT, HBsAg/HBeAg serum conversion rate, the INF-gamma expression level in peripheral blood mononuclear cells (PBMC), the amount of HBV-specific CTL, the change of expression level of peripheral cytokines (IL-4,IL-10,IL-12 and INF-gamma) against the baseline level.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

The following conditions must be met for all enrolled subjects:

  1. Aged 18-65 years with either sex;
  2. HBV serology meet the following criteria:

    • HBsAg-positive lasting for at least 6 months at the time of screening;
    • HBeAg-positive at the time of screening;
    • Serum HBV DNA≥1.0×10E5 copies/ml at the time of screening
  3. 80U/L<ALT<400U/L;
  4. TBIL<40μmol/L;
  5. No YMDD mutation of the HBV drug resistance gene
  6. Subjects agree not to participate in any other clinical trial or take any other anti-HBV therapeutics during the study;
  7. Subjects understand and sign the ICF which approved by EC, and are able to comply with the study procedures and complete the study.

Exclusion Criteria:

Subjects meeting the following conditions will not be enrolled in the study:

  1. Was suspected with HCC by the following evidence:

    • B-Ultrasound or imaging which shows occupying lesions;
    • Continuingly elevating serum AFP level even if the B-Ultrasound is normal;
    • AFP >100ng/ml;
  2. With acute hepatic decompensation caused by liver disease aggravation or with clinical symptoms of decompensated liver disease at baseline;
  3. Serum Cr≥1.5mg/dl (≥130μmol/l) at the time of screening;
  4. Serum amylase > two-fold of the upper limit of the normal reference value;
  5. Hb (male<100g/ L, female<90g/L), WBC<3.5×10E9/L,PLT<60×10E9/L (except hypersplenism and cirrhosis);
  6. Co-infection with HCV (anti-HCV positive), HIV and anti-HAV IgM positive, anti-HDV IgM positive, anti-HEV IgM positive, anti-CMV IgM positive and autoimmune hepatitis (e.g. antinuclear antibody titer>1:160 ) or other active liver disease caused by known or unknown factors;
  7. Any other serious disease or active diseases other than hepatitis B that are considered by investigators to be potential factors that may interfere with the therapy, assessment or compliance with the protocol, including any uncontrolled diseases with clinical significance, e.g. kidney, heart, lung, blood vessel, neurogenic, digestive system and metabolic diseases (diabetes, hyperthyroidism, adrenal gland diseases), autoimmune dysfunctions, and tumors, etc;
  8. History of alcohol or drug abuse that is considered by investigators that could affect subject's compliance with the protocol or could influence the result of the analysis;
  9. Pregnant or breast-feeding female subjects, or those who plan to be pregnant during the course of the study or male subjects' companions who plan to be pregnant during the course of the study;
  10. Having used immunosuppressive agents, immunomodulators (thymosin), cytotoxic drugs within 6 months or transaminase-decreasing drugs within one month prior to the initiation of this study;
  11. Having used anti-HBV drugs (Lamivudine, interferon, adefovir, entecavir, or sebivo, etc.) within 6 months prior to the initiation of this study;
  12. Had or planning to have liver transplantation;
  13. Having received experimental drug treatment from any other study within 3 months prior to the screening;
  14. Allergic to nucleoside drugs or nucleoside analogues;
  15. Not agreeing to the study protocol or any other factors considered not eligible for this study by investigators.
  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: NCT01189656

Locations
China, Beijing
Department of Infections Disease of Peking University First Hospital
Beijing, Beijing, China, 100034
Sponsors and Collaborators
The 458 Hospital of Chinese PLA
Guangzhou Baidi Biotechnology Co., Ltd
Guangzhou Pharmaceucal Company Limited
Investigators
Principal Investigator: Yu Yanyan, Professor SFDA
  More Information

No publications provided

Responsible Party: Guangming Chen, The 458 Hospital of Chinese PLA
ClinicalTrials.gov Identifier: NCT01189656     History of Changes
Other Study ID Numbers: 71007.02
Study First Received: August 25, 2010
Last Updated: August 26, 2010
Health Authority: China: Food and Drug Administration

Keywords provided by The 458 Hospital of Chinese PLA:
Chronic hepatitis B patients

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Chronic
Digestive System Diseases
DNA Virus Infections
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases

ClinicalTrials.gov processed this record on October 23, 2014