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

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

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.

Study Overview

• Status: Terminated
• Conditions: Gastroenteritis
• Intervention / Treatment: Biological: Placebo; Biological: HIL-214

Detailed Description

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
• Enrollment (Actual): 3084
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Colombia
  • Distrito Capital
    • Bogotá, Distrito Capital, Colombia
      • Policlínico Social del Norte
  • Valle Del Cauca
    • Cali, Valle Del Cauca, Colombia, 760042
      • Cntro de Estudios en Infectologia Pediatrica (CEIP)
• Dominican Republic
  • Santo Domingo, Dominican Republic
    • Clínica Cruz Jiminian
  • Santo Domingo, Dominican Republic, 11102
    • Hospital General Regional Marcelino Velez Santana
  • Santo Domingo, Dominican Republic
    • CAIMED - Dominican Center for Clinical Studies
  • Santo Domingo, Dominican Republic
    • Fundacion Dominicana de Perinatologia Pro Bebe
  • Distrito Nacional
    • Santo Domingo, Distrito Nacional, Dominican Republic
      • Hospital Pediátrico Dr. Hugo Mendoza
• Honduras
  • San Pedro Sula, Honduras
    • DEMEDICA
  • Tegucigalpa, Honduras
    • INVERIME - Inversiones en Investigación Medica
  • Tegucigalpa, Honduras
    • Investigación Sin Limite
• Panama
  • Ciudad de Panamá, Panama
    • CEVAXIN Av. México
  • La Chorrera, Panama
    • Cevaxin La Chorrera
  • Panama City, Panama, 00831
    • CEVAXIN 24 Decembre
  • Chiriqui
    • David, Chiriqui, Panama, 00507
      • CEVAXIN David
• Peru
  • Lima, Peru, 15024
    • Instituto de Investigacion Nutricional
• Puerto Rico
  • Guayama, Puerto Rico
    • Clinical Research Puerto Rico
• United States
  • Texas
    • Houston, Texas, United States, 77065
      • DM Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 months to 5 months (Child)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; One dose of placebo on Day 1 and one dose of placebo between Day 28 and Day 56.	Biological: Placebo; 2 injections - given on Day 1 and the second given between Day 29 - Day 57
Experimental: Experimental; One dose of HIL-214 on Day 1 and one dose of HIL-214 between Day 28 and Day 56.	Biological: HIL-214; 2 injections - given on Day 1 and the second given between Day 29 - Day 57

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	The duration of the primary observation period was 6 months starting at 28 days post dose 2.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Time to first occurrence during the primary observation period* of moderate/severe AGE case associated with GI.1 or GII.4 norovirus genotypes, irrespective of other gastrointestinal pathogens. 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.	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 Any Norovirus Genogroup (GI or GII), Irrespective of Other Gastrointestinal Pathogens	Time to first occurrence during the primary observation period of moderate/severe AGE case associated with any norovirus genogroup (GI or GII), irrespective of other gastrointestinal pathogens. 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. Vaccine efficacy (VE) estimates and 95% confidence intervals (CIs) are also reported.	The duration of the primary observation period was 6 months starting at 28 days post dose 2.
Immunogenicity of HIL-214 Compared to Placebo	The percentage of participants with a predefined seroresponse (≥4-fold rise in antibody concentration) at up to 56 days post dose 1 (Visit 2), 28 days post dose 2 (Visit 3), and/or at 1 year of age (visit 4) to the GI.1 and GII.4c components of HIL-214 and 95% confidence interval are reported. HBGA-blocking and pan-Ig assays were used for immunogenicity analyses	Participant reaches 1 year of age
Safety of HIL-214 Compared to Placebo - Solicited Local Adverse Events (AEs)	Percentage of participants with solicited local (injection site) adverse events (AEs) within 7 days of vaccine administration. Assessed AEs include injection site pain, erythema, induration, and swelling.	Up to 7 days after each dose of HIL-214 or placebo.
Safety of HIL-214 Compared to Placebo - Solicited Systemic Adverse Events (AEs)	Percentage of participants with solicited systemic AEs within 7 days of vaccine administration. Assessed AEs include drowsiness, irritability/fussiness, loss of appetite, vomiting, and diarrhea.	Up to 7 days after each dose of HIL-214 or placebo.
Safety of HIL-214 Compared to Placebo - Adverse Events (AEs) Leading to Vaccine Withdrawal	Percentage of participants with AEs leading to trial vaccine dose withdrawal.	Up to 28 days after first dose of HIL-214 or placebo.
Safety of HIL-214 Compared to Placebo - Adverse Events (AEs) Leading to Trial Withdrawal.	Percentage of participants with AEs leading to trial withdrawal.	From Day 1 to end of the trial/early termination.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity Objectives	Titer results for HBGA blocking antibody test	Through 28 days post Dose 2
Immunogenicity Objectives - Secondary	Titer results for Pan-Ig antibody test	Through 28 days post Dose 2
Solicited Local AEs	The number of subjects with solicited local AEs	Up to 7 days after each dose
Solicited Systemic AEs	The number of subjects with solicited systemic AEs	Up to 7 days after each dose
Unsolicited Symptomatic AEs	The number of subjects with unsolicited symptoms AEs	Up to 28 days after each dose
AEs Leading to Withdrawal	The number AEs that lead to vaccine dose withdrawal	Up to 28 days after each dose
Adverse Events and Serious Adverse Events	The number of AEs and SAEs that lead to the subject's withdrawal from the trial	Day 1 through end of trial, up to 2 years

Collaborators and Investigators

• Sponsor: HilleVax

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2022
• Primary Completion (Actual): December 28, 2023
• Study Completion (Actual): September 30, 2024

Study Registration Dates

• First Submitted: February 17, 2022
• First Submitted That Met QC Criteria: March 10, 2022
• First Posted (Actual): March 16, 2022

Study Record Updates

• Last Update Posted (Actual): July 10, 2025
• Last Update Submitted That Met QC Criteria: July 8, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis
• Other Study ID Numbers: NOR-212

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No