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

• ClinicalTrials.gov Identifier: NCT02777411
• Recruitment Status: Completed
• First Posted: May 19, 2016
• Last Update Posted: November 30, 2016
• Sponsor: Enimmune Corporation
• Information provided by (Responsible Party): Enimmune Corporation

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Enterovirus Infections	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)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 122 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: 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
• Study Start Date: December 2014
• Actual Primary Completion Date: January 2016
• Actual Study Completion Date: January 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Solicited adverse events [ Time Frame: 7 days after each vaccination ]
2. Unsolicited adverse events [ Time Frame: 28 days after each vaccination ]
3. The occurrence of overall adverse events (AEs) and serious adverse event (SAEs) [ Time Frame: Day 0 to Day 196 ]

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 6 Months to 6 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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.

Contacts and Locations

Locations

Taiwan

China Medical University Hospital

Taichung, Taiwan

National Taiwan University Hospital

Taipei, Taiwan

Taipei Veterans General Hospital

Taipei, Taiwan

Linkou Chang Gung Memorial Hospital

Tao Yuan, Taiwan

Sponsors and Collaborators

Enimmune Corporation

More Information

• Responsible Party: Enimmune Corporation
• ClinicalTrials.gov Identifier: NCT02777411
• Other Study ID Numbers: EV-RB1401
• First Posted: May 19, 2016
• Last Update Posted: November 30, 2016
• Last Verified: August 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Enimmune Corporation:

Vaccines; Hand, Foot and Mouth Disease; EV71 enteroviruses vaccine

Additional relevant MeSH terms:

Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Virus Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs