Safety and Immunogenicity of High-dose IN-B001 in Healthy Subjects

Study Overview
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Brief Summary
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This study aims to evaluate the safety and immunogenicity of high-dose IN-B001 after administration in healthy subjects

Detailed Description
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Enterovirus 71(EV71) and coxsackievirus A16(CVA16) are major causes of Hand-foot-and-mouth disease (HFMD) occurring in pediatric population. Although EV71 vaccine has been licensed in China, vaccine for CVA16-associated HFMD is currently not available anywhere. The purpose of this phase I study is to evaluate the safety and immunogenicity of EV71/CVA16 bivalent vaccine in healthy adults.

Official Title
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A Randomized, Double-blind, Placebo-controlled, Phase 1 Clinical Trial to Investigate the Safety and Immunogenicity of High-dose IN-B001 After Administration in Healthy Subjects

Conditions
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Hand, Foot and Mouth Disease

Intervention / Treatment
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* Biological: IN-B001 EV71 A dose
* Biological: IN-B001 CVA16 B dose
* Biological: IN-B001 Bivalent C dose
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult aged ≥19 to <50 years at the time of screening tests Body mass index(BMI) of ≥18.0 kg/m2 to ≤27.0 kg/m2, with body weight of ≥55.0 kg to ≤90.0 kg for men and ≥50.0 kg to ≤90.0 kg for women at the time of screening tests Determined by the investigator to be eligible for study participation based on the results of screening tests Intact deltoid muscle that allows administration of the investigational product Consent to use medically acceptable contraception throughout the study Negative finding from a pregnancy test (urine hCG) at the time of the screening for women of childbearing potential Voluntary decision and provision of written consent on participation in this study Exclusion Criteria: History of a hand-foot-mouth disease or history of a disease related with enterovirus(EV) infection within 3 months prior to the 1st IP administration Medical history of an anaphylactic or similar acute reaction to IN-B001 or similar vaccine Febrile disease or infectious disease within 2 weeks prior to the 1st IP administration Whole blood donation within 2 months or apheresis within 1 month prior to the 1st IP administration Vaccination with other prevention vaccine within 2 months prior to the 1st IP administration Use of an immunomodulator or immunosuppressant within 3 months prior to the 1st IP administration History of a Guillain Barre syndrome Excessive caffeine intake or continuous alcohol consumption or incapable of abstention from alcohol during the study Participation in other clinical trial within 6 months prior to the 1st IP administration Pregnant or breastfeeding women Clinically significant hepatic, renal, neurological, respiratory, endocrine, hematology and oncology, cardiovascular, urological or psychiatric disease or such history Positive serological finding (type B hepatitis test, type C hepatitis test, human immunodeficiency virus(HIV) test) History of drug abuse or positive finding from a urine screening test for an abusive drug Use or of any prescription medication or oriental medicine within 2 weeks or any over-the-counter(OTC) medication, health functional food or vitamin within 1 week prior to the 1st IP administration or expected use of such products Administration of a blood product or blood-derived agent within 3 months prior to the 1st IP administration Determined by the investigator to be ineligible for study participation due to other reason including clinical laboratory findings

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IN-B001 EV71 A dose<br>Inactivated EV71 vaccine(A dose) or placebo in 10 healthy adults (three doses, 28 days interval) | Biological: IN-B001 EV71 A dose<br>* Inactivated vaccine against EV71, three doses, 28 days interval<br>Biological: Placebo<br>* Placebo, three doses, 28 days interval<br>|
| Experimental: IN-B001 CVA16 B dose<br>Inactivated CVA16 vaccine(B dose) or placebo in 10 healthy adults (three doses, 28 days interval) | Biological: IN-B001 CVA16 B dose<br>* Inactivated vaccine against CVA16, three doses, 28 days interval<br>Biological: Placebo<br>* Placebo, three doses, 28 days interval<br>|
| Experimental: IN-B001 Bivalent C dose<br>Inactivated EV71/CVA16 vaccine(C dose) or placebo in 10 healthy adults (three doses, 28 days interval) | Biological: IN-B001 Bivalent C dose<br>* Inactivated vaccine against EV71/CVA16, three doses, 28 days interval<br>Biological: Placebo<br>* Placebo, three doses, 28 days interval<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency and severity of adverse events of IN-B001 (Safety of IN-B001) | Frequency and severity of adverse events up to 32 weeks post first dose | Week 0 to Week 32 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity of IN-B001: Anti-EV71 IgG titer | Serum EV71-specific IgG titers | Week 0 to Week 32 | 
| Immunogenicity of IN-B001 : Anti-CVA16 IgG titer | Serum CVA16-specific IgG titers | Week 0 to Week 32 | 
| Immunogenicity of IN-B001 : Geometric mean titer (GMT) of EV71 neutralizing antibody titers | Geometric mean titers based on neutralizing antibody titers. Measurement of fold-increase over baseline of neutralizing titers against EV71 | Week 0 to Week 32 | 
| Immunogenicity of IN-B001 : GMT of CVA16 neutralizing antibody titers | Geometric mean titers based on neutralizing antibody titers. Measurement of fold-increase over baseline of neutralizing titers against CVA16 | Week 0 to Week 32 |