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

This study has been completed.
Sponsor:
Collaborator:
Shenzhen Kangtai Biological Products Co., LTD
Information provided by (Responsible Party):
Jiangsu Province Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier:
NCT01203319
First received: September 15, 2010
Last updated: April 21, 2012
Last verified: April 2012
  Purpose

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.


Condition Intervention Phase
Hepatitis b
Biological: 60mcg/1.0ml recombinant hepatitis B vaccine
Biological: 30mcg/1.0ml recombinant hepatitis B vaccine
Biological: 10mcg/1.0ml recombinant hepatitis B vaccine
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Prevention
Official Title: The Immunogenicity and Safety of 60mcg and 30mcg Recombinant Hepatitis B Vaccines in People Aged 16 and Older Who Failed to Respond to Routine Administration of 10mcg Recombinant Hepatitis B Vaccines

Resource links provided by NLM:


Further study details as provided by Jiangsu Province Centers for Disease Control and Prevention:

Primary Outcome Measures:
  • Immunogenicity of Recombinant Hepatitis B Vaccines in Nonresponders [ Time Frame: one month after the second vaccination ] [ Designated as safety issue: No ]
    Quantitative detection of anti-HBs using ratio-immunity method on serum obtained one month after second vaccination

  • Immunogenicity of Recombinant Hepatitis B Vaccines in Nonresponders [ Time Frame: one month after the third vaccination ] [ Designated as safety issue: No ]
    Quantitative detection of anti-HBs using ratio-immunity method on serum obtained one month after third vaccination


Secondary Outcome Measures:
  • Immunogenicity of Recombinant Hepatitis B Vaccines in Nonresponders [ Time Frame: one month after the first vaccination ] [ Designated as safety issue: No ]
    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 Nonresponders [ Time Frame: within the first 30 days after first vaccination ] [ Designated as safety issue: Yes ]
    assessment of the local and systemic adverse reaction within the first 30 days after first vaccination

  • the Safety of Recombinant Hepatitis B Vaccines in Nonresponders [ Time Frame: within the first 30 days after second vaccination ] [ Designated as safety issue: Yes ]
    assessment of the local and systemic adverse reaction within the first 30 days after second vaccination

  • the Safety of Recombinant Hepatitis B Vaccines in Nonresponders [ Time Frame: within the first 30 days after third vaccination ] [ Designated as safety issue: Yes ]
    assessment of the local and systemic adverse reaction within the first 30 days after third vaccination


Enrollment: 1091
Study Start Date: November 2006
Study Completion Date: March 2011
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 60mcg/1.0ml recombinant hepatitis B vaccine
600 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.
Biological: 60mcg/1.0ml recombinant hepatitis B vaccine
to receive 60mcg/1.0ml recombinant HBV vaccines on day 0, 30 and 60
Experimental: 30mcg/1.0ml recombinant hepatitis B vaccine
600 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.
Biological: 30mcg/1.0ml recombinant hepatitis B vaccine
to receive 30mcg/1.0ml recombinant hepatitis B vaccines on day 0, 30 and 60.
Placebo Comparator: 10mcg/1.0ml recombinant hepatitis B vaccine
300 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.
Biological: 10mcg/1.0ml recombinant hepatitis B vaccine
to receive 10mcg/1.0ml recombinant hepatitis B vaccines on day 0, 30 and 60

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.

  Eligibility

Ages Eligible for Study:   16 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria :

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

  • Healthy subjects aged 16 and older as established by medical history and clinical examination
  • The subjects or their guardians are able to understand and sign the informed consent
  • Had never received the hepatitis B vaccines
  • Subjects who can and will comply with the requirements of the protocol

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

  • Healthy subjects aged 16 and older as established by medical history and clinical examination
  • The subjects or their guardians are able to understand and sign the informed consent
  • After the routine administration of 10mcg hepatitis B vaccines, the peak period levels of anti-HBs is lower than 10mIU/ml
  • Subjects with temperature <37.1°C on axillary setting
  • Subjects who can and will comply with the requirements of the protocol

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
  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: NCT01203319

Sponsors and Collaborators
Jiangsu Province Centers for Disease Control and Prevention
Shenzhen Kangtai Biological Products Co., LTD
Investigators
Principal Investigator: Feng-Cai Zhu, Master Jiangsu Provincial Center for Diseases Control and Prevention
  More Information

No publications provided by Jiangsu Province Centers for Disease Control and Prevention

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Jiangsu Province Centers for Disease Control and Prevention
ClinicalTrials.gov Identifier: NCT01203319     History of Changes
Other Study ID Numbers: KT0003
Study First Received: September 15, 2010
Results First Received: March 29, 2012
Last Updated: April 21, 2012
Health Authority: China: Food and Drug Administration

Keywords provided by Jiangsu Province Centers for Disease Control and Prevention:
immunogenicity
safety
recombinant hepatitis B vaccine
nonresponders

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
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