A Study to Evaluate the Immunogenicity and Safety of EV71 Vaccine in Pediatric Subjects

An Open-Label, Dose-Finding, Phase II Study to Evaluate the Immunogenicity and Safety of the Bioreactor-generated EV71 Vaccine in Pediatric Subjects Aged 3 to 6 Years and 2 to 35 Months Old

The objectives of this study are to evaluate the immune response and safety profiles of two injections of EV71 vaccine administrated with or without adjuvant Al(OH)3 at 0.5-μg and 1-μg dose in children aged 3 to 6 years old and 2 to 35 months old infants/toddlers.

Study Overview

• Status: Completed
• Conditions: Enterovirus Infections
• Intervention / Treatment: Biological: EV71 vaccine ([0.5 μg total protein + adjuvant 150 μg AI(OH)3] per dose); Biological: EV71 vaccine ([1 μg total protein + adjuvant 150 μg AI(OH)3] per dose); Biological: EV71 vaccine ([1 μg total protein ] per dose)

• Study Type: Interventional
• Enrollment (Actual): 140
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Taichung, Taiwan
    • China Medical University Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taipei, Taiwan
    • Taipei Veterans General Hospital
  • Taoyuan, Taiwan
    • Linkou Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 6 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Healthy children aged from 3 to 6 years old (i.e. ≥ 3 years old and < 7 years old) for Part A,and from 2 to 35 months old (i.e. ≥ 2 months old and < 36 months old) for Part B at the time of first vaccination.
2. Subject's guardians are able and willing to comply with study procedures and provide the signed informed consent.
3. Subject is able and can comply with the requirements of the protocol.
4. Subject with body temperature ≤38°C.

Exclusion Criteria:

1. Subject with previous known exposure to Enterovirus 71 (EV71).
2. Subject with a history of herpangina, hand-foot-mouth disease,and acute hemorrhagic conjunctivitis associated with enterovirus infection in the past 3 months.
3. Subject with gestation < 37 weeks.
4. Subject with birth weight <2.5 kg.
5. Subject with a history of hypersensitivity to vaccines, or a history of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
6. Family history of seizures or progressive neurological disease.
7. Family history of congenital or hereditary immunodeficiency.
8. Severe malnutrition or dysgenopathy.
9. Major congenital defects or serious chronic illness, including perinatal brain damage.
10. Subject diagnosed of having autoimmune disease (e.g., celiac disease, type I diabetes, lupus (SLE), juvenile dermatomyositis, scleroderma, juvenile idiopathic arthritis (JIA), immune (or idiopathic) thrombocytopenia purpura).
11. Bleeding disorder diagnosed by a doctor or significant bruising or hemostatic difficulties with IM injections or blood draws.
12. Any acute infections 7 days prior to administrating the first vaccination.
13. Use of any investigational product (including drug, vaccine) within 30 days prior to vaccination or planned use during the study period.
14. Administration of any vaccines within 14 days prior to randomization.
15. Use of immunoglobulins or any blood products within 3 months prior to vaccination or planned use during the study period.
16. Chronic administration (defined as > 14 days) of immunosuppressants or other immunomodulators or systemic corticosteroids within 6 months prior to vaccination or planned use during the study period.
17. Subjects who had ever received investigational EV-71 vaccine prior to randomization.
18. Under anti-tuberculosis prevention or therapy.
19. Any condition that in the opinion of the investigator may interfere with the evaluation of study objectives.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A1; 3 to 6 years	Biological: EV71 vaccine ([0.5 μg total protein + adjuvant 150 μg AI(OH)3] per dose); Two vaccinations at 28 days apart
Experimental: Group A2; 3 to 6 years	Biological: EV71 vaccine ([1 μg total protein + adjuvant 150 μg AI(OH)3] per dose); Two vaccinations at 28 days apart
Experimental: Group A3; 3 to 6 years	Biological: EV71 vaccine ([1 μg total protein ] per dose); Two vaccinations at 28 days apart
Experimental: Group B1; 2 to 35 months	Biological: EV71 vaccine ([0.5 μg total protein + adjuvant 150 μg AI(OH)3] per dose); Two vaccinations at 28 days apart
Experimental: Group B2; 2 to 35 months	Biological: EV71 vaccine ([1 μg total protein + adjuvant 150 μg AI(OH)3] per dose); Two vaccinations at 28 days apart
Experimental: Group B3; 2 to 35 months	Biological: EV71 vaccine ([1 μg total protein ] per dose); Two vaccinations at 28 days apart

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum neutralizing antibody titers (NT) induced by the EV71 vaccine	Evaluate the immunogenicity change of serum neutralizing antibody titers induced by the EV71 vaccine from baseline on Day 56	Day 56
Seroconversion rate (SCR) based on neutralizing antibody titers	Evaluate the immunogenicity change of SCR from baseline on Day 56	Day 56
Serum neutralizing antibody titers (NT) induced by the EV71 vaccine	Evaluate the immunogenicity change of serum neutralizing antibody titers induced by the EV71 vaccine from baseline on Day 28	Day 28
Serum neutralizing antibody titers (NT) induced by the EV71 vaccine	Evaluate the immunogenicity change of serum neutralizing antibody titers induced by the EV71 vaccine from baseline on Day 196	Day 196
Seroconversion rate (SCR) based on neutralizing antibody titers	Evaluate the immunogenicity change of SCR from baseline on Day 28	Day 28
Seroconversion rate (SCR) based on neutralizing antibody titers	Evaluate the immunogenicity change of SCR from baseline on Day 196	Day 196

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Solicited adverse events		7 days after each vaccination
Unsolicited adverse events		28 days after each vaccination
The occurrence of overall adverse events (AEs) and serious adverse event (SAEs)		Day 0 to Day 196
The occurrence of EV 71 breakthrough infection after Visit 3		Day 57 to Day 364
Serum neutralizing antibody titers (NT) induced by the EV71 vaccine	Evaluate the immunogenicity of serum neutralization antibody titer induced by the EV 71 vaccine on Day 364	Day 364

Collaborators and Investigators

• Sponsor: Enimmune Corporation

Publications and helpful links

General Publications

• Hung MC, Cho CY, Chen CJ, Lai CC, Wu KG. Immunogenicity and safety of an inactivated enterovirus A71 vaccine in children 3-6 years and 2-35 months of age- an open-label, randomized phase IIb clinical trial. Vaccine. 2019 Sep 3;37(37):5559-5566. doi: 10.1016/j.vaccine.2019.07.096. Epub 2019 Aug 6.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2016
• Primary Completion (Actual): August 1, 2017
• Study Completion (Actual): December 1, 2017

Study Registration Dates

• First Submitted: August 4, 2016
• First Submitted That Met QC Criteria: August 29, 2017
• First Posted (Actual): August 31, 2017

Study Record Updates

• Last Update Posted (Actual): October 26, 2021
• Last Update Submitted That Met QC Criteria: October 18, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Vaccines; Hand, Foot and Mouth Disease; Foot-and-Mouth Disease; EV71 vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Picornaviridae Infections; Enterovirus Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: EV-BR1501

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO