Efficacy and Safety of Two Doses of HIL-214 in Children

Study Overview
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Brief Summary
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This is a randomized, placebo-controlled study that is being done to evaluate the safety and effectiveness of two doses of the HIL-214 vaccine compared to a placebo. The study will enroll 3000 children who will be 5 months of age at the time of the first dose study vaccine. The second dose of study vaccine will be given 28 days after the first dose.

Detailed Description
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Noroviruses have emerged as the single most significant cause of gastroenteritis in both middle-high income countries and low resource settings worldwide. Those most at risk of severe illness include the very young, the elderly and immunocompromised individuals. Noroviruses are highly infectious, highly resistant to environmental conditions, and have multiple routes of transmission including person-to-person, food-borne and contaminated surfaces. Noroviruses can cause acute, mild to severe illness characterized by vomiting, diarrhea, fever, dehydration and abdominal pain, representing a significant burden to public health. The clinical presentation in adults and older children is similar. While mortality due to acute gastroenteritis (AGE) caused by norovirus in the pediatric population is rare in industrialized countries, it is more common in developing countries. Although potentially a cause for hospitalization in very young children, there are fewer cases during the first 6 months of life possibly due to the protection offered by maternal antibodies from trans-placental transfer and in breast milk. In addition, norovirus infections have significant socioeconomic impact on hospitals, schools, day care centers and other closed settings. As the burden of rotavirus in children decreases due to successful rotavirus vaccination programs in infants, norovirus infections are increasingly recognized as the primary cause of AGE in many countries around the world.

Official Title
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A Phase 2b, Double-blind, Randomized, Multi-site, Placebo-controlled Trial to Evaluate the Efficacy, Safety and Immunogenicity of Intramuscular HIL-214 Norovirus Vaccine in Healthy Children 5 Months of Age at Initial Vaccination

Conditions
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Gastroenteritis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria The subject should be 5 months of age (within plus or minus 14 days) male or female Children 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 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 Children whose LARs can and are willing to comply with trial procedures and are available for the duration of follow-up Exclusion Criteria Clinically significant abnormality in growth by height, weight, or head circumference (according to local 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 Known hypersensitivity or allergy to any of the investigational vaccine components (including excipients) Any clinically significant active infection (as assessed by the investigator) or temperature ≥38.0°C (>100.4°F), within 3 days of intended trial vaccination Any serious chronic or progressive disease according to the judgment of the investigator (e.g., cardiac, renal or hepatic disease) Individuals with 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 in the trial Known or suspected impairment/alteration of immune function Subjects with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time Subjects who received or are scheduled to receive any other vaccines within 14 days (for inactivated vaccines and oral polio vaccine) or 28 days (for other live vaccines) before or after any dose of trial vaccine Subjects participating in any clinical trial with another investigational product 30 days prior to first trial visit or intend to participate in another clinical trial at any time during the conduct of this trial Subjects known to be positive for or in evaluation for possible human immunodeficiency virus infection Subject's LAR or subject's first-degree relatives involved in the trial conduct

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
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 | The number of subjects with moderate to severe AGE cases associated with GI.1 or GII.4 NoV genotypes. | From 4 weeks after second vaccination through the end of the surveillance period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Objective | The number of subjects with moderate to severe AGE associated only with ANY NoV genotypes | From 4 weeks after second vaccination through the end of the surveillance period |