Clinical trial NCT02367664: A Clinical Trial for Inactivated Japanese Encephalitis Vaccine in Healthy Chinese Infants
Official title: A Single-centre Phase III Clinical Trial for Vero Cell-derived Inactivated Japanese Encephalitis Vaccine Produced by Shandong Hengye Biotech Co., Ltd. in Healthy Chinese Infants Aged 6-11 Months, Aimed to Evaluate Immunogenicity and Safety
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Encephalitis
Keywords: Japanese encephalitis
immunogenicity
safety
vaccine
Lead sponsor: Jiangsu Province Centers for Disease Control and Prevention
Sponsor class: NETWORK
Collaborators: name: Shandong Hengye Biotech Co., Ltd.
First posted: 2015-02-20
Enrollment: 900
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Japanese encephalitis (JE) is an acute viral zoonotic disease. Neurologic manifestations of the disease range from subtle changes in behavior to serious problems, including blindness, ataxia, weakness, and movement disorders. The Japanese encephalitis virus (JEV) occurs primarily in Southeast Asian. It is spread by culicine mosquitoes, most often Culex tritaeniorhynchus. Its incubation period is 5 to 15 days.In China, JE epidemic peak season is from June to August and it mainly occurred in children. JE has ranked in top ten infectious diseases according to either incidence or mortality. JE vaccines are used to protect the population especially young children and infants from encephalitis diseases. Live attenuated JE vaccines are now widely used. They are directly produced from attenuated virus which may increase the possibility of virulence reversion. Many developed countries are using purified model inactivated JE vaccine. Therefore, it is an inevitable trend in China to develop a new generation of safer and more effective inactivated vaccine to prevent and control epidemic encephalitis.

Detailed description: Japanese encephalitis (JE) is an acute viral zoonotic disease. Neurologic manifestations of the disease range from subtle changes in behavior to serious problems, including blindness, ataxia, weakness, and movement disorders. The Japanese encephalitis virus (JEV) occurs primarily in Southeast Asian. It is spread by culicine mosquitoes, most often Culex tritaeniorhynchus. Its incubation period is 5 to 15 days. In China, JE epidemic peak season is from June to August and it mainly occurred in children. JE has ranked in top ten infectious diseases according to either incidence or mortality. JE vaccines are used to protect the population especially young children and infants from encephalitis diseases. Live attenuated JE vaccines are now widely used. They are directly produced from attenuated virus which may increase the possibility of virulence reversion. Many developed countries are using purified model inactivated JE vaccine. Therefore, it is an inevitable trend in China to develop a new generation of safer and more effective inactivated vaccine to prevent and control epidemic encephalitis.

In order to evaluate immunogenicity and safety of Vero cell-derived inactivated Japanese Encephalitis vaccine produced by Shandong Hengye Biotech Co., Ltd. a single-centre phase III clinical trial is planned to conduct in healthy infants aged 6-11 months in China.

There will be two immunization programs. 600 healthy infants aged 6-11 months will be randomly assigned (1:1) to receive an experimental vaccine or a positive control vaccine at day 0,7. Another 300 healthy infants aged 6-11 months will be recruited to receive an experimental vaccine at day 0,28. All of them will be received a third dose as booster vaccination 12 months later.

Eligibility criteria: Inclusion Criteria:

* Aged from 6 to 11 months old on the day of inclusion
* Had never received any Japanese Encephalitis vaccine
* Subjects' legal guardians are able to understand and sign the informed consent
* In good general health judged from medical history and clinical examination at the time of inclusion
* Subjects and legal guardians can and will comply with the requirements of the protocol
* Subjects with temperature \<=37.0°C on axillary setting

Exclusion Criteria:

* Subject who has a medical or family history of any of the following: allergic history, seizure, epilepsy, brain or mental disease
* Subject who is allergic to any ingredient of the vaccine
* Family history of congenital or hereditary immunodeficiency
* Subject with damaged or low immune function which has already been known
* Subject who had a Japanese Encephalitis medical history
* Subject with acute febrile illness or infectious disease
* Major congenital defects or serious chronic illness, including perinatal brain damage
* Thrombocytopenia, blood coagulation disorder or bleeding difficulties with intramuscular injection
* Subject who has serious allergic history
* Subject with other medical history not suitable for vaccination such as fainting during injection or acupuncture treatment
* Any prior administration of immunodepressant or corticosteroids in last 6 months
* Any prior administration of blood products in last 3 months
* Any prior administration of other research medicine/vaccine in last 30 days
* Any prior administration of any attenuated live vaccine in last 30 days
* Any prior administration of subunit or inactivated vaccines in last 14 days, such as pneumococcal vaccine
* Any acute infection or serious infection needing systemic antibiotics or antiviral treatment in last 7 days
* Any fever with temperature \>=38.0°C on axillary setting in last 3 days
* Any medical, psychological, social or other condition judged by investigator, that may interfere subject's compliance with the protocol or signature on informed consent

Primary outcomes:
measure: positive seroconversion rate of JE neutralizing antibody following primary vaccination
timeFrame: 28 days after primary vaccination
measure: incidence of solicited adverse reactions (including systemic and local adverse reactions) following primary vaccination
timeFrame: 0-7 days after primary vaccination
Secondary outcomes:
measure: GMT of JE neutralizing antibody following primary vaccination
timeFrame: 28 days after primary vaccination
measure: positive seroconversion rate of JE neutralizing antibody following booster vaccination
timeFrame: 28 days after booster vaccination
measure: positive seroconversion rate of JE neutralizing antibody following primary vaccination
timeFrame: 12 months after primary vaccination
measure: incidence of unsolicited adverse reactions (including systemic and local adverse reactions) following primary vaccination
timeFrame: 0-28 days after primary vaccination
measure: incidence of adverse event (AE) following booster vaccination
timeFrame: 0-28 days after booster vaccination
measure: incidence of serious adverse event (SAE) during the whole study period
timeFrame: Day 0 of the first dose up to Day 28 of the third dose
measure: GMT of JE neutralizing antibody following booster vaccination
timeFrame: 28 days after booster vaccination
measure: GMT of JE neutralizing antibody following primary vaccination
timeFrame: 12 months after primary vaccination
Other outcomes:
Locations:
city: Xuzhou
country: China
facility: Pizhou Center for Disease Control and Prevention
state: Jiangsu
Study officials:
References: