Clinical trial NCT03274102: Safety and Immunogenicity of Concomitant Administration of EV71 Vaccine With EPI Vaccines
Official title: A Randomized, Controlled Clinical Trial to Evaluate the Safety and Immunogenicity of Concomitant Administration of EV71 Vaccine With Recombinant Hepatitis B Vaccine/Group A Meningococcal Polysaccharide Vaccine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hand, Foot and Mouth Disease
Keywords: Inactivated Enterovirus Type 71 (EV71) Vaccine
Concomitant vaccination
Safety
Immunogenicity
Infant
Lead sponsor: Sinovac Biotech Co., Ltd
Sponsor class: INDUSTRY
Collaborators: name: Guangdong Center for Disease Prevention and Control
First posted: 2017-09-06
Enrollment: 780
Sex: ALL
Minimum age (years): 6
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to evaluate the safety and immunogenicity of concomitant administration of EV71 vaccine with recombinant hepatitis B vaccine/Group A meningococcal polysaccharide vaccine.

Detailed description: This study is an open-label, single-center, randomized, comparative phase IV clinical trial. The purpose of this study is to evaluate the safety and immunogenicity of concomitant administration of EV71 vaccine manufactured by Sinovac (Beijing) Vaccine Technology Co., Ltd. with recombinant hepatitis B vaccine/Group A meningococcal polysaccharide vaccine. 780 healthy infants of 6 months old as participants are randomly assigned into three experimental groups in the ratio 1:1:1. The group I receive EV71 Vaccine (first dose)\& recombinant hepatitis B vaccine on day 0 and EV71 vaccine (second dose)\& Group A meningococcal polysaccharide vaccine on day 30. The group II receive recombinant hepatitis B vaccine on day 0 and Group A meningococcal polysaccharide vaccine on day 30. The group III receive the first and second dose of EV71 Vaccine on day 0 and day 30 respectively.

Eligibility criteria: Inclusion Criteria:

* Healthy volunteers aged 6 months
* Finished two doses of vaccination (0,1 month) of hepatitis B vaccine prior to study entry
* Proven legal identity
* Guardian(s) of the volunteer should be capable of understanding the written consent form, and such form should be signed before the infant being included into this study

Exclusion Criteria:

* Finished all the three doses vaccination (0,1,6 month) of hepatitis B vaccine prior to study entry
* Prior vaccination of meningococcal polysaccharide vaccine
* Prior vaccination of EV71 vaccine
* Unable to receive vaccination on both arms
* History of hand foot and mouth disease
* Previously tested HBsAg positive
* Mother of the subject had been previously tested HBsAg positive
* History of asthma; history of allergy to any vaccine or vaccine ingredient, or serious adverse reaction(s) to vaccination, such as urticaria, difficulty in breathing, angioneurotic edema, abdominal pain, etc
* Congenital malformation, developmental disorders, genetic defects
* Autoimmune disease or immunodeficiency/immunosuppressive
* Severe nervous system disease or mental illness
* Diagnosed coagulation function abnormal (e.g., coagulation factor deficiency, coagulation disorder, or platelet abnormalities) , or obvious bruising or coagulation disorders
* Any immunosuppressant, cytotoxic medicine, or inhaled corticosteroids (except corticosteroid spray for treatment of allergic rhinitis or corticosteroid treatment on surface for acute non-complicated dermatitis) within 6 month prior to study entry
* Receipt of blood product (e.g., immunoglobulin) within 3 months prior to study entry
* Receipt of any other investigational medicine(s) within 30 days prior to study entry
* Receipt of any live attenuated vaccine within 14 days prior to study entry
* Receipt of any subunit vaccine or inactivated vaccine within 7 days prior to study entry
* Acute disease or acute stage of chronic disease within 7 days prior to study entry
* Axillary temperature \> 37.0 ℃
* Any other factor that suggesting the volunteer is unsuitable for this study based on the judgement of investigators

Exclusion Criteria of the Second Injection:

* Subjects with one of the following 1 to 3 conditions are forbidden to continue vaccination, while the other study steps could be carried out based on the judgement of investigator; for subjects with one of the following 4 to 5 conditions, whether to continue vaccination are determined by the investigator; for subjects with one of the following 6 to 7 conditions, vaccination may be delayed in the time window specified in the study:

  1. Any serious adverse event that has a causal relationship with the investigated vaccine (except the group II)
  2. Severe allergic reactions or hypersensitivity after vaccination (including urticaria / rash appear within 30 minutes after vaccination, except the group II )
  3. Any confirmed or suspected autoimmune disease or immunodeficiency disease (e.g., HIV infection)
  4. New chronic diseases or acute stage of chronic diseases
  5. Other reactions (including severe pain, severe swelling, severe activity limitation, persistent hyperthermia, severe headache or other systemic or local reactions) determined by the investigators
  6. Acute diseases (moderate or severe diseases with or without fever)
  7. Axillary temperature\> 37.0 ℃

Primary outcomes:
measure: The seropositive rate of EV71 neutralizing antibody, anti-HBs and serum bactericidal antibody 1 month after 2 doses of vaccination
timeFrame: 30 days after 2 doses of injection
Secondary outcomes:
measure: Incidence of solicited local or systemic adverse events within 7 days after each dose
timeFrame: 7 days after each dose of injection
measure: Incidence of unsolicited local or systemic adverse events within 30 days after each dose
timeFrame: 30 days after each dose of injection
measure: Incidence of serious adverse events during the period of safety monitoring
timeFrame: 60 days after the first dose injection
measure: The seroconversion rate of EV71 neutralizing antibody, anti-HBs and serum bactericidal antibody(SBA) 1 month after 2 doses of vaccination
timeFrame: 30 days after 2 doses of injection
measure: EV71 neutralizing antibody GMT, anti-HBs GMC and SBA antibody GMT 1 month after 2 doses of vaccination
timeFrame: 30 days after 2 doses of injection
Other outcomes:
Locations:
city: Dongguan
country: China
facility: Dongguan Municipal Center for Disease Control and Prevention
state: Guangdong
Study officials:
affiliation: Guangdong Center for Disease Prevention and Control
name: Huizhen Zheng
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhang Z, Liang Z, Zeng J, Zhang J, He P, Su J, Zeng Y, Fan R, Zhao D, Ma W, Zeng G, Zhang Q, Zheng H. Immunogenicity and Safety of an Inactivated Enterovirus 71 Vaccine Administered Simultaneously With Hepatitis B Vaccine and Group A Meningococcal Polysaccharide Vaccine: A Phase 4, Open-Label, Single-Center, Randomized, Noninferiority Trial. J Infect Dis. 2019 Jul 2;220(3):392-399. doi: 10.1093/infdis/jiz129.