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

Phase 3TerminatedNCT05281094

HilleVax3,084 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

3,084

Conditions

Gastroenteritis

Interventions

HIL-214BIOLOGICAL

2 injections - given on Day 1 and the second given between Day 29 - Day 57

PlaceboBIOLOGICAL

2 injections - given on Day 1 and the second given between Day 29 - Day 57

Eligibility

Sex: ALLMin age: 5 MonthsMax age: 5 MonthsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (17)

DM Clinical Research

Houston, Texas, United States

Policlinico Social del Norte

Bogotá, Bogota D.C., Colombia

Outcomes

Primary Outcomes

To Demonstrate the Efficacy of HIL-214 Vaccine Against Moderate/Severe Acute Gastroenteritis (AGE) Associated Only With GI.1 or GII.4 Norovirus Genotypes.

Time to first occurrence during the primary observation period, of moderate/severe AGE case associated only with GI.1 or GII.4 norovirus genotypes. Vaccine efficacy (VE) is defined as 100% \[1- (λV/λC)\], where λV and λC denote the hazard rates of the primary endpoint AGE case for the HIL 214 and placebo arms, respectively. The primary endpoint AGE case is defined as at least 3 loose or liquid stools OR at least 2 or more episodes of vomiting OR 1 or more loose or liquid stools plus 1 or more vomiting episodes in any 24-hour period. The presence of norovirus in onset stool samples was assessed by RT-PCR and norovirus-positive samples were genotyped by sequencing. Samples that were positive for GI.1 or GII.4 genotypes were further analyzed for the presence of co-pathogens. VE estimates and 95% confidence intervals (CIs) are also reported.

Time frame: The duration of the primary observation period was 6 months starting at 28 days post dose 2.

Secondary Outcomes

To Evaluate the Efficacy of HIL-214 Vaccine Against Moderate/Severe Acute Gastroenteritis (AGE) Associated Only With Any Norovirus (GI or GII) Genogroup.

Time to first occurrence during the primary observation period, of moderate/severe AGE case associated with any (GI or GII) genogroup Vaccine efficacy (VE) is defined as 100% \[1- (λV/λC)\], where λV and λC denote the hazard rates of the primary endpoint AGE case for the HIL 214 and placebo arms, respectively. The endpoint AGE case is defined as at least 3 loose or liquid stools OR at least 2 or more episodes of vomiting OR 1 or more loose or liquid stools plus 1 or more vomiting episodes in any 24-hour period. The presence of norovirus in onset stool samples was assessed by RT-PCR and norovirus positive samples were genogrouped by sequencing. Samples that were positive for GI or GII genogroups were further analyzed for the presence of co-pathogens. Vaccine efficacy (VE) estimates and 95% confidence intervals (CIs) are also reported.

Time frame: The duration of the primary observation period was 6 months starting at 28 days post dose 2.

To Evaluate the Efficacy of HIL-214 Vaccine Against Moderate/Severe Acute Gastroenteritis (AGE) Associated With GI.1 or GII.4 Norovirus Genotypes, Irrespective of Other Gastrointestinal Pathogens.

Data from ClinicalTrials.gov

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