A Study to Evaluate the Safety and Immunogenicity of EV71 Vaccine in Pediatric Subjects Aged 3 to 6 Years and 6 to 35 Months Old

An Open-label, Dose-finding, Phase II Study to Evaluate the Safety and Immunogenicity of EV71 Vaccine in Pediatric Subjects Aged 3 to 6 Years and 6 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 AlPO4 at 0.5-μg, 1-μg, 2-μg and 5-μg dose (if required) in children aged 3 to 6 years old and 0.25-μg (if required), 0.5-μg, 1-μg and 2-μg (if required) in 6 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 AIPO4] per dose); Biological: EV71 vaccine ([1 μg total protein + adjuvant 150 μg AIPO4] per dose); Biological: EV71 vaccine ([2 μg total protein + adjuvant 150 μg AIPO4] per dose); Biological: EV71 vaccine (2 μg total protein per dose); Biological: EV71 vaccine (1 μg total protein per dose)

• Study Type: Interventional
• Enrollment (Actual): 122
• 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
  • Tao Yuan, Taiwan
    • Linkou Chang Gung Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 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; from 6 to 35 months old (i.e. ≥ 6 months old and < 36 months old) for Part B at the time of first vaccination.
2. Subject's guardians were able and willing to comply with study procedures and give written informed consent.
3. Subject was able and could 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, 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 bleeding difficulties with IM injections or blood draws.
12. Any acute infections 7 days prior to administrate 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 attenuated live vaccine within 7 days prior to vaccination.
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.
17. Under anti-tuberculosis prevention or therapy.
18. 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
• Masking: NONE

Number of Arms

7

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 AIPO4] 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 AIPO4] per dose); Two vaccinations at 28 days apart
EXPERIMENTAL: Group A3; 3 to 6 years	Biological: EV71 vaccine ([2 μg total protein + adjuvant 150 μg AIPO4] per dose); Two vaccinations at 28 days apart
EXPERIMENTAL: Group A4; 3 to 6 years	Biological: EV71 vaccine (2 μg total protein per dose); Two vaccinations at 28 days apart
EXPERIMENTAL: Group B2; 6 to 35 months	Biological: EV71 vaccine ([0.5 μg total protein + adjuvant 150 μg AIPO4] per dose); Two vaccinations at 28 days apart
EXPERIMENTAL: Group B3; 6 to 35 months	Biological: EV71 vaccine ([1 μg total protein + adjuvant 150 μg AIPO4] per dose); Two vaccinations at 28 days apart
EXPERIMENTAL: Group B4; 6 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	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

Secondary Outcome Measures

Outcome Measure	Time Frame
immunoglobulin G (IgG) titers induced by the EV71 vaccine ( determined by ELISA)	Day 28, Day 56, Day 196
serum neutralizing antibody titers (NT) induced by the EV71 vaccine	Day 28, Day 56, Day 196
Seroconversion rate (SCR) based on neutralizing antibody titers	Day 28, Day 56, Day 196
change in the laboratory results based on hematology tests in each visit	Day 28, Day 56, Day 196
change in the laboratory results based on biochemistry tests in each visit	Day 28, Day 56, Day 196
change in heart rates at each visit (for the 3 to 6 years old group only)	Day 28, Day 56, Day 196
change in blood pressures at each visit (for the 3 to 6 years old group only)	Day 28, Day 56, Day 196

Collaborators and Investigators

• Sponsor: Enimmune Corporation

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (ACTUAL): January 1, 2016
• Study Completion (ACTUAL): January 1, 2016

Study Registration Dates

• First Submitted: May 16, 2016
• First Submitted That Met QC Criteria: May 18, 2016
• First Posted (ESTIMATE): May 19, 2016

Study Record Updates

• Last Update Posted (ESTIMATE): November 30, 2016
• Last Update Submitted That Met QC Criteria: November 28, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Vaccines; Hand, Foot and Mouth Disease; EV71 enteroviruses 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-RB1401

Plan for Individual participant data (IPD)

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