Safety and Immunogenicity of Concomitant Administration of EV71 Vaccine With Expanded Programme on Immunization Vaccines

• ClinicalTrials.gov Identifier: NCT04111432
• Recruitment Status: Recruiting
• First Posted: October 1, 2019
• Last Update Posted: October 1, 2019
• Sponsor: Sinovac Biotech Co., Ltd
• Collaborators: Shaanxi Provincial Center for Disease Control and Prevention; Hanbin District Center for Disease Control and Prevention
• Information provided by (Responsible Party): Sinovac Biotech Co., Ltd

Study Description

Brief Summary:

The purpose of this study is to evaluate the safety and immunogenicity of concomitant administration of EV71 vaccine with measles mumps, and rubella combined live attenuated vaccine/ encephalitis live attenuated vaccine.

Condition or disease	Intervention/treatment	Phase
Hand, Foot and Mouth Disease	Biological: Concomitant administration of EV71vaccine with EPI vaccines; Biological: Single injection of EPI vaccine; Biological: EV71 Vaccine only	Phase 4

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 andimmunogenicity of concomitant administration of EV71 vaccine manufactured by Sinovac (Beijing) Vaccine Technology Co., Ltd. with measles mumps, and rubella combined live attenuated vaccine/ encephalitis live attenuated vaccine. 360 healthy infants of 8 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)&measles mumps, and rubella combined live attenuated vaccine on day 0 and EV71 vaccine (second dose)&encephalitis live attenuated vaccine on day 30. The group II receive measles mumps, and rubella combined live attenuated vaccine on day 0 and encephalitis live attenuated vaccine on day 30. The group III receive the first and second dose of EV71 Vaccine on day 0 and day 30 respectively.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 372 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: A Randomized, Controlled Clinical Trial to Evaluate the Safety and Immunogenicity of Concomitant Administration of EV71 Vaccine With Measles, Mumps, and Rubella Combined Live Attenuated Vaccine/ Encephalitis Live Attenuated Vaccine
• Actual Study Start Date: July 26, 2019
• Estimated Primary Completion Date: November 2019
• Estimated Study Completion Date: March 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Group I-EV71 and EPI vaccines Concomitant administration; EV71 Vaccine (intramuscular injection,0.5ml,first dose)/measles mumps, and rubella combined live attenuated vaccine (subcutaneous injection,0.5ml) on day 0 and EV71 Vaccine (intramuscular injection, 0.5ml,second dose)/ encephalitis live attenuated vaccine (subcutaneous injection, 0.5ml) on day 30	Biological: Concomitant administration of EV71vaccine with EPI vaccines; The investigated EV17 vaccine was manufactured by Sinovac Biotech Co., Ltd.# the MMR vaccine was manufactured by Shanghai Institute of Biological Products Co.,Ltd.; the Live attenuated Japanese encephalitis vaccine was manufactured by Chengdu Institute of Biological Products Co.,Ltd.
Active Comparator: Group II-EPI vaccine only Single injection of EPI vaccine: measles mumps, and rubella combined live attenuated vaccine (subcutaneous injection,0.5ml) on day 0 and encephalitis live attenuated vaccine (subcutaneous injection, 0.5ml) on day 30	Biological: Single injection of EPI vaccine; The MMR vaccine was manufactured by Shanghai Institute of Biological Products Co.,Ltd.; the Live attenuated Japanese encephalitis vaccine was manufactured by Chengdu Institute of Biological Products Co.,Ltd.
Active Comparator: Group III-EV71 vaccine only EV71 Vaccine only; the first and second dose of EV71 Vaccine (intramuscular injection,0.5ml) on day 0 andday 30 respectively	Biological: EV71 Vaccine only; The investigated EV17 vaccine was manufactured by Sinovac Biotech Co., Ltd.

Outcome Measures

Primary Outcome Measures :

1. The seroconversion rates（SCR） of the EV71 neutralizing antibody 30 days after two dose of EV71 vaccines [ Time Frame: 30 days after two dose of EV71 vaccines ]
   Immunogenicity indicator

Secondary Outcome Measures :

1. The seroconversion rates（SCR） of the Measles IgG antibody，Rubella 30 IgG antibody and Mumps IgG antibody 60 days after one dose of MMR vaccine [ Time Frame: 60 days after one dose of MMR vaccine ]
   Immunogenicity indicator
2. The seroconversion rates（SCR） of the Japanese encephalitis neutralizing antibody 30 days after one dose of Encephalitis B vaccine [ Time Frame: 30 days after one dose of Encephalitis B vaccine ]
   Immunogenicity indicator
3. EV71 neutralizing antibody positive rate 30 days of two dose of EV71 vaccines [ Time Frame: 30 days after two dose of EV71 vaccines ]
   Immunogenicity indicator
4. The Geometric mean titer (GMT) of the EV71 neutralizing antibody 30 days of two dose of EV71 vaccines [ Time Frame: 30 days after two dose of EV71 vaccines ]
   Immunogenicity indicator
5. Measles IgG antibody，Rubella 30 IgG antibody and Mumps IgG antibody positive rate 60 days after one dose of MMR vaccine [ Time Frame: 60 days after one dose of MMR vaccine ]
   Immunogenicity indicator
6. The Geometric mean titer (GMT) of Measles IgG antibody，Rubella 30 IgG antibody and Mumps IgG antibody 60 days after one dose of MMR vaccine [ Time Frame: 60 days after one dose of MMR vaccine ]
   Immunogenicity indicator
7. The Japanese encephalitis neutralizing antibody positive rate 30 days after one dose of Encephalitis B vaccine [ Time Frame: 30 days after one dose of Encephalitis B vaccine ]
   Immunogenicity indicator
8. The Geometric mean titer (GMT) of Japanese encephalitis neutralizing antibody 30 days after one dose of Encephalitis B vaccine [ Time Frame: 30 days after one dose of Encephalitis B vaccine ]
   Immunogenicity indicator
9. Incidence of solicited local or systemic adverse events within 7 days or 14 days after each dose [ Time Frame: 7 days or 14 days after each dose of injection ]
   Safety indicator
10. The incidences of adverse reactions after each does [ Time Frame: 0-30 days after each dose ]
    After each dose, a 30-minute safety observation will be conducted immediately. The body temperature, solicited local and general adverse events (AE) on day 0-7 or day 0-14 were reported. Unsolicited adverse events on day 0-30 were also reported.
11. Incidence of serious adverse events (SAEs) during the period of safety monitoring [ Time Frame: 0-30 days after each dose ]
    Serious adverse events (SAEs) will be collected during the period of safety monitoring after each dose

Eligibility Criteria

• Ages Eligible for Study: 8 Months and older (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Healthy volunteer aged ≥ 8 months;
• Proven legal identity;
• Guardians of the participants 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:

• Prior vaccination with EV71 vaccine;
• Prior vaccination with MMR vaccine or vaccine including mumps or measles or mumps or rubella vaccine components;
• Prior vaccination with Encephalitis B vaccine；
• Cannot be vaccinated with both arms at the same time；
• History of hand，foot and mouth disease;
• History of measles or mumps or rubella or encephalitis B；
• Allergy to gentamicin; history of allergy to any vaccine or vaccine ingredient, or serious adverse reaction(s) to vaccination, such as urticaria,difficulty in breathing, angioneurotic edema, pain, etc;
• Congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc;
• Autoimmune diseases or immunodeficiency/immunosuppression;
• Severe neurological disorders (epilepsy, convulsions or convulsions) or psychosis;
• History of thyroidectomy, absence of spleen, functional absence of spleen, and any circumstances leading to absence of spleen or splenectomy;
• 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) in the past 6 months;

• Receipt of any of the following products:

  1. Blood product within 3 months prior to study entry;
  2. Any live attenuated vaccine within 14 days prior to study entry;
  3. Any subunit vaccine or inactivated vaccine within 7 days prior to study entry;
  4. Any other study drugs within 30 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 opinions of investigators.

Contacts and Locations

Contacts

Contact: Shaobai Zhang; 86-02982695467; maolyzhang@163.com

Locations

China, Shaanxi

Hanbin District Center for Disease Control and Prevention; Recruiting

Ankang, Shaanxi, China, 725000

Contact: Heng Wu 86-18309153222 174462924@qq.com

Sponsors and Collaborators

Sinovac Biotech Co., Ltd

Shaanxi Provincial Center for Disease Control and Prevention

Hanbin District Center for Disease Control and Prevention

Investigators

• Principal Investigator: Shaobai Zhang; Shaanxi Provincal Center for Disease Control and Preventione

More Information

• Responsible Party: Sinovac Biotech Co., Ltd
• ClinicalTrials.gov Identifier: NCT04111432
• Other Study ID Numbers: EV71-SN-2019-01
• First Posted: October 1, 2019
• Last Update Posted: October 1, 2019
• Last Verified: September 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sinovac Biotech Co., Ltd:

Inactivated Enterovirus Type 71 (EV71) Vaccine; Concomitant vaccination; Safety; Immunogenicity; Infant

Additional relevant MeSH terms:

Foot-and-Mouth Disease; Hand, Foot and Mouth Disease; Mouth Diseases; Stomatognathic Diseases; Picornaviridae Infections; RNA Virus Infections; Virus Diseases; Coxsackievirus Infections; Enterovirus Infections; Vaccines; Immunologic Factors; Physiological Effects of Drugs