Clinical trial NCT01203319: The Immunogenicity and Safety of 60mcg/30mcg Recombinant Hepatitis B Vaccines in People Who Failed to Respond to Routine Administration of Hepatitis B Vaccines
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Hepatitis b
Keywords: immunogenicity
safety
recombinant hepatitis B vaccine
nonresponders
Lead sponsor: Jiangsu Province Centers for Disease Control and Prevention
Sponsor class: NETWORK
Collaborators: name: Shenzhen Kangtai Biological Products Co., LTD
First posted: 2010-09-16
Enrollment: 1091
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: 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.

Eligibility 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

Primary outcomes:
measure: Immunogenicity of Recombinant Hepatitis B Vaccines in Nonresponders
timeFrame: one month after the second vaccination
measure: Immunogenicity of Recombinant Hepatitis B Vaccines in Nonresponders
timeFrame: one month after the third vaccination
Secondary outcomes:
measure: Immunogenicity of Recombinant Hepatitis B Vaccines in Nonresponders
timeFrame: one month after the first vaccination
measure: the Safety of Recombinant Hepatitis B Vaccines in Nonresponders
timeFrame: within the first 30 days after first vaccination
measure: the Safety of Recombinant Hepatitis B Vaccines in Nonresponders
timeFrame: within the first 30 days after second vaccination
measure: the Safety of Recombinant Hepatitis B Vaccines in Nonresponders
timeFrame: within the first 30 days after third vaccination
Other outcomes:
Locations:
Study officials:
affiliation: Jiangsu Provincial Center for Diseases Control and Prevention
name: Feng-Cai Zhu, Master
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pan HX, Zeng Y, Song XF, Zhang YJ, Xu K, Liang ZL, Zhu FC. Immune response to hepatitis B vaccine with high antigen content in non-responders after standard primary vaccination in Chinese adults. Vaccine. 2014 Jun 17;32(29):3706-12. doi: 10.1016/j.vaccine.2014.02.094. Epub 2014 Mar 27.