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The Immunogenicity and Safety of 60mcg/30mcg Recombinant Hepatitis B Vaccines in People Who Failed to Respond to Routine Administration of Hepatitis B Vaccines

Phase 2
Completed
Conditions
Hepatitis b
Interventions
Biological: 60mcg/1.0ml recombinant hepatitis B vaccine
Biological: 30mcg/1.0ml recombinant hepatitis B vaccine
Biological: 10mcg/1.0ml recombinant hepatitis B vaccine
Registration Number
NCT01203319
Lead Sponsor
Jiangsu Province Centers for Disease Control and Prevention
Brief Summary

This study is an expanded Phase 2/Phase 3 clinical trial base on the safety data obtained from the phase 1 clinical trial. The purpose of this study is to further evaluate the immunogenicity and safety of 60mcg/30mcg recombinant hepatitis B vaccines in people aged 16 and older who failed to respond to routine administration of 10mcg recombinant hepatitis B vaccines and to explore the optimizing immunizing dose and immune procedure.

Detailed Description

The most effective method to prevent hepatitis B virus infection is to receive the vaccination of hepatitis b vaccine to get the protective antibody anti-HBs. Both the blood-derived hepatitis B vaccine and the recombinant hepatitis B vaccines have been proved to be effective and safe since the application in 1981 and 1989 respectively. Previous passive or active immunization testes indicated that the lowest effective level of anti-HBs for prevention of infection is 10mIU/ml. However there are still some recipients can't generate expected level of anti-HBs after the vaccinations. In adults, there are 5% to 10% recipients will failed to respond to routine administration of 10mcg recombinant hepatitis B vaccines, and those nonresponders are susceptible population even after the vaccinations. In this study, a recipient whose peak period (1 month after vaccination) levels of anti-HBs is lower than 10mIU/ml after finishing the vaccinations of 3 dose 10mcg hepatitis b vaccines is called nonresponders.

Nowadays, a lot tests are conducted on nonresponders to help them generate the protective antibody anti-HBs, including increase the antigen dosage of vaccines, increase the injections of vaccines, change the route of inoculation and the use of adjuvant. Unfortunately, these previous studies can not get coincident and persuasive outcomes due to the small sample size and poor representativeness. This study is plan to evaluate the immunogenicity and safety of 60mcg/30mcg recombinant hepatitis B vaccines in people aged 16 and older who failed to respond to routine administration of 10mcg recombinant hepatitis B vaccines and to provide the scientific evidences for the revaccination strategy in China.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1091
Inclusion Criteria

Not provided

Exclusion Criteria

Filter period: The subjects to receive first 10mcg recombinant hepatitis B vaccines:

  • Subject that has a medical history of any of the following: allergic history, or allergic to any ingredient of vaccine
  • Family history of seizures or progressive neurological disease
  • Family history of congenital or hereditary immunodeficiency
  • Women of pregnancy, lactation or about to be pregnant in 60 days
  • Autoimmune disease or immunodeficiency
  • Bleeding disorder diagnosed by a doctor or significant bruising or bleeding difficulties with IM injections or blood draws
  • Any prior administration of administration of immunoglobulins

Filter period: The subjects to receive second or/and third 10mcg recombinant hepatitis B vaccines:

  • Any reaction or hypersensitivity to the recombinant hepatitis B vaccines after the vaccinations
  • Serious adverse reactions to vaccines
  • Active infections
  • Subjects who want to quit the study
  • Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives

Revaccination period: The nonresponders to receive first 60mcg recombinant hepatitis B vaccines:

  • Qualitative test of Anti-HBs, HBsAg or Anti-HBc on serum is positive
  • Any reaction or hypersensitivity to the recombinant hepatitis B vaccines after the vaccinations
  • Family history of seizures or progressive neurological disease
  • Family history of congenital or hereditary immunodeficiency
  • Women of pregnancy, lactation or about to be pregnant in 60 days
  • Autoimmune disease or immunodeficiency
  • Bleeding disorder diagnosed by a doctor or significant bruising or bleeding difficulties with IM injections or blood draws
  • Any prior administration of immunoglobulins, any other vaccines or experimental drugs in the last 7days
  • Any active infections and received any antibiotic or anti-virus treatments in the last 7 days
  • Had a fever in the last 3 days, with temperature ≥37.1°C
  • Participate in another clinical trials
  • Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives

Revaccination period: The nonresponders to receive second or/and third 60mcg recombinant hepatitis B vaccines:

  • Any reaction or hypersensitivity to the recombinant hepatitis B vaccines after the vaccinations
  • Serious adverse reactions to vaccines
  • Active infections
  • Subjects who want to quit the study
  • Any condition that in the opinion of the investigator, may interfere with the evaluation of study objectives

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
60mcg/1.0ml recombinant hepatitis B vaccine60mcg/1.0ml recombinant hepatitis B vaccine600 participants aged 16 and older who failed to respond to routine administration of 10mcg recombinant hepatitis B vaccines to receive 60mcg/1.0ml recombinant hepatitis B vaccines on day 0, 30 and 60.
30mcg/1.0ml recombinant hepatitis B vaccine30mcg/1.0ml recombinant hepatitis B vaccine600 participants aged 16 and older who failed to respond to routine administration of 10mcg recombinant hepatitis B vaccines to receive 30mcg/1.0ml recombinant hepatitis B vaccines on day 0, 30 and 60.
10mcg/1.0ml recombinant hepatitis B vaccine10mcg/1.0ml recombinant hepatitis B vaccine300 participants aged 16 and older who failed to respond to routine administration of 10mcg recombinant hepatitis B vaccines to receive 10mcg/1.0ml recombinant hepatitis B vaccines on day 0, 30 and 60.
Primary Outcome Measures
NameTimeMethod
Immunogenicity of Recombinant Hepatitis B Vaccines in Nonrespondersone month after the third vaccination

Quantitative detection of anti-HBs using ratio-immunity method on serum obtained one month after third vaccination

Secondary Outcome Measures
NameTimeMethod
Immunogenicity of Recombinant Hepatitis B Vaccines in Nonrespondersone month after the first vaccination

Quantitative detection of anti-HBs using ratio-immunity method on serum obtained one month after first vaccination

the Safety of Recombinant Hepatitis B Vaccines in Nonresponderswithin the first 30 days after third vaccination

assessment of the local and systemic adverse reaction within the first 30 days after third vaccination

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