Safety and Immunogenicity of HIL-214 With Routine Pediatric Vaccines

Study Overview
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Brief Summary
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This is a phase 2, multi-country, randomized, double-blind, placebo-controlled trial to evaluate the immune response to routine pediatric vaccinations when co-administered with HIL-214 or placebo in healthy infants. This trial will also evaluate the safety profile of a 2-dose regimen of HIL-214 co-administered with routine pediatric vaccines.

Detailed Description
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Epidemiologic studies have shown that gastroenteritis in infants is associated with several viruses, including norovirus, sapovirus and rotavirus. These viruses together or individually can be associated with illness ranging from asymptomatic to serious. Asymptomatic infection can create a reservoir, allowing further spread of the virus, whereas serious illness can lead to death, particularly in the very young, very old or immunocompromised. 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 acute gastroenteritis (AGE) in many countries around the world. Currently, there is no available vaccine to counter the disease burden associated with norovirus. Vaccinating at an early age would reduce the severe illness in young children and also reduce the asymptomatic cases which act as a vehicle for transmission within the population. As infants already receive multiple vaccines during the first months of life, an additional vaccination must fit into the immunization scheme in a convenient way for compliance. It must also have an acceptable safety profile and be immunogenic without interfering with the immune response to routine childhood vaccines.

Official Title
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A Phase 2, Multi-country, Randomized, Double-blind, Placebo-controlled Trial to Evaluate Safety and Immunogenicity When HIL-214 is Concomitantly Administered With Routine Pediatric Vaccines in Healthy Infants

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 is aged 2 months (+14 days). Male or female. 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 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. Infants 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). Severe reaction to routine childhood vaccine(s) administered at Visit 1. 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 licensed or authorized vaccines not planned in this trial within 14 days (for inactivated vaccines) or within 28 days (for live vaccines) before or after any dose of trial vaccine. Note: Flu and/or COVID vaccine can be administered per local guidelines at any time during the trial. Subjects participating in any clinical trial with another investigational product 30 days prior to first trial visit or due 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: 2 Months
Maximum Age: 2 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 |
| --- | --- |
| Experimental: Experimental<br>HIL-214 (1 dose at 4 months of age and 1 dose at 6 months of age) and routine childhood vaccines according to schedule. | Biological: HIL-214<br>* 2 injections - given at 4 months and the second at 6 months of age.<br>|
| Placebo Comparator: Placebo<br>Placebo (1 dose at 4 months of age and 1 dose at 6 months of age) and routine childhood vaccines according to schedule. | Biological: Placebo<br>* 2 injections - given at 4 months and the second at 6 months of age.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Immunogenicity Response | Evaluate the immune response to each licensed pediatric vaccine (DTaP-Hib-IPV-HepB, RV1, and PCV13) co-administered with a 2-dose regimen of HIL-214 at 4 and 6 months of age, compared to that of the routine pediatric vaccines co-administered with placebo. Outcome measures: Binary (yes/no) variable indicating anti-DT immunoglobulin G (IgG) concentration ≥0.1 IU/mL. Binary variable indicating anti-TT IgG concentration ≥0.1 IU/mL. Anti-pertussis [FHA], [PRN] and [PTX]) IgG concentrations. Binary variable indicating anti-poliovirus neutralizing antibody titers ≥1:8, Binary variable indicating anti-Haemophilus influenzae type b Binary variable indicating anti-hepatitis b surface antigen Anti-pneumococcal IgG concentrations for certain serotypes Anti-RV1 IgA concentrations. | 6 months |