Safety and Immunogenicity of HIL-214 in Healthy Japanese Infants

Study Overview
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Brief Summary
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This is a phase 1, randomized, double-blind multi-center, placebo-controlled trial in Japan to evaluate the safety and immunogenicity of HIL-214 in healthy infants 5 months of age (-14/+14 days) at first trial vaccine administration. In this protocol, because the trial is blinded, trial vaccine refers to both the investigational vaccine (HIL-214) and placebo.

Detailed Description
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The rationale for trial NOR-109 is to evaluate the safety and immunogenicity of HIL-214 in Japanese pediatric subjects and establish whether the data obtained is consistent with that previously obtained for non-Japanese pediatric subjects. The clinical trials for HIL-214 have so far been performed in Europe, the United States and several countries in Latin America [26]. The incidence rate of norovirus-attributable disease in Japan is at least as high as in other developed countries with the highest rates occurring in children below the age of 5 years and hospitalization most common in very young and very old populations. The inclusion of infants (5 months [±14 days] of age at the time of first trial vaccine administration) serves to compare the data obtained for infants of non-Japanese descent with Japanese infants, in alignment with the global clinical program, and to support the inclusion of Japanese infants into phase 3. Enrollment and vaccination of the infants will be performed either before or after the required routine childhood vaccines per the national immunization schedule. This phase 1 trial in Japan aims to assess the safety and immunogenicity of two doses of HIL-214 administered 4 to 8 weeks apart, in 21 healthy infants aged 5 months at the time of the first trial vaccine dose administration. A placebo arm is included to allow an unbiased assessment of safety and immunogenicity.

Official Title
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A Phase 1, Randomized, Double-blind, Multi-center, Placebo-controlled Trial to Evaluate the Safety and Immunogenicity of the Intramuscular Norovirus GI.1/GII.4 Bivalent VLP Vaccine in Healthy Japanese Infants 5 Months of Age at First Trial Vaccine Administration

Conditions
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Gastroenteritis

Intervention / Treatment
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* Biological: Placebo
* Biological: HIL-214


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Male or female subject aged 5 months [-14/+14 days]. Infants who are in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs) and clinical judgment of the investigator. The subject's legally acceptable representative (LAR) signs and dates a written, informed consent form (ICF) and any required privacy authorization prior to the initiation of any trial procedures, after the nature of the trial has been explained according to local regulatory requirements. The subject's LAR is willing and able to comply with trial procedures and is available for the duration of follow-up. Exclusion Criteria Clinically significant abnormality in growth by length/height, weight, or head circumference (according to national guidelines). Gastrointestinal abnormalities or any chronic gastrointestinal disease, including any uncorrected congenital malformation of the gastrointestinal tract according to medical history and/or physical examination. Chronic use of oral corticosteroids (equivalent to 20 mg/day prednisolone for ≥12 weeks / ≥2 mg/kg body weight /day for ≥2 weeks) within 60 days prior to Visit 1 (use of inhaled, intranasal, or topical corticosteroids are allowed). Use of parenteral corticosteroids (equivalent to 20 mg/day prednisolone for ≥12 weeks / ≥2 mg/kg body weight /day for ≥2 weeks. Use of inhaled, intranasal, or topical corticosteroid is allowed) within 60 days prior to Visit 1. Receipt of immunostimulants within 60 days prior to Visit 1. Receipt of parenteral, epidural, or intra-articular immunoglobulin (Ig) preparations, blood products, and/or plasma derivatives within 90 days prior to Visit 1 or planned during the full duration of the trial. Receipt of immunosuppressive therapy prior to Visit 1. Known hypersensitivity or allergy to any of the trial vaccine components (including excipients). Any clinically significant active infection (as assessed by the investigator) or temperature ≥38.0°C (>100.4°F), regardless of method used, within 3 days prior to intended trial vaccine administration. Gastroenteritis within 7 days before planned dosing (can warrant delay of trial vaccine administration). History of, e.g., convulsions/febrile convulsions, or any illness, that, in the opinion of the investigator, might interfere with the results of the trial or pose additional risk to the subjects due to participation the trial. Abnormalities of splenic or thymic function. Known or suspected impairment/alteration of immune function. Known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time. Receipt or scheduled receipt of any other approved or authorized vaccines within 14 days (for all non-live vaccines or oral live vaccines) or 28 days (for parenteral live vaccines) before or after trial vaccine administration. Participation in any clinical trial with another investigational product 30 days prior to first trial visit or intention to participate in another clinical trial at any time during the conduct of this trial. Seropositive for, or in evaluation for, possible human immunodeficiency virus infection.

Ages Eligible for Study
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Minimum Age: 5 Months
Maximum Age: 5 Months

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: Parallel Assignment
Interventional Model Description: Subjects will be allocated (2 to1) into one of two trial arms, Arm 1 - One dose of HIL-214; Arm 2 - One dose of placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>One dose of placebo on Day 1 and one dose of placebo between Day 29 and Day 57 | Biological: Placebo<br>* 2 injections - given on Day 1 and the second given between Day 29 - Day 57<br>|
| Experimental: Experimental<br>One dose of HIL-214 on Day 1 and one dose of HIL-214 between Day 29 and Day 57 | Biological: HIL-214<br>* 2 injections - given on Day 1 and the second given between Day 29 - Day 57<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Objective | All of the subjects in this trial will be assessed for safety of HIL-214 by comparing the occurrence and intensity of solicited and unsolicited local and systemic reactions to the study vaccine compared with placebo vaccination and including AEs leading to withdrawal of trial vaccine. | 3 months | 
| Number of subjects with solicited local AEs | Subjects that present with solicited systemic AEs. | up to 7 days post-dose 1 and dose 2. | 
| Number of subjects with solicited Systemic AEs | Subjects that present with solicited systemic AEs. | up to 7 days post-dose 1 and dose 2. | 
| Number of subjects with unsolicited symptomatic AEs | Subjects that present with unsolicited symptoms (AEs) | up to 28 days post-dose 1 and dose 2. | 
| Number of subjects with AEs leading to withdrawal | The number of AEs that lead to vaccine dose withdrawal. | Up to 56 days post-dose 1 | 
| Number of subjects with Adverse Events and Serious Adverse Events | The number of AEs and SAEs that lead to the subject's withdrawal from the trial | Through study completion, an average of 1 year. |