GastroenteritisPhase 2/3NCT05281094
Efficacy and Safety of Two Doses of HIL-214 in Children
A Phase 2/3 study testing HIL-214 in people with Gastroenteritis, run by HilleVax at 17 sites in 7 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 5 to 5 monthsHealthy volunteers can take part
- Conditions the study is for
- Gastroenteritis
- What is being tested?
- HIL-214
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 3,084 participants
- Where
- 17 sitesin 7 countries
- Study dates
- 28 Apr 2022to 30 Sep 2024
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 5 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
17 sites in 7 countries.
17 sites in 7 countries
Dominican Republic5 sites
Hospital Pediátrico Dr. Hugo Mendoza
Santo Domingo, Nacional
Hospital General Regional Marcelino Velez Santana
Santo Domingo, 11102
CAIMED - Dominican Center for Clinical Studies
Santo Domingo
Clínica Cruz Jiminian
Santo Domingo
Fundacion Dominicana de Perinatologia Pro Bebe
Santo Domingo
Panama4 sites
CEVAXIN David
David, Chiriquí Province, 00507
CEVAXIN La Chorrera
La Chorrera
CEVAXIN 24 Decembre
Panama City, 00831
CEVAXIN Av. México
Panama City
Honduras3 sites
Demedica
San Pedro Sula
INVERIME - Inversiones en Investigación Medica
Tegucigalpa
Investigación Sin Limite
Tegucigalpa
Colombia2 sites
Policlinico Social del Norte
Bogotá, Bogota D.C.
Cntro de Estudios en Infectologia Pediatrica (CEIP)
Cali, Valle del Cauca Department, 760042
About this study
Official title: 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.
Read the 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.
- Conditions
- Gastroenteritis
- Being tested
- HIL-214, Placebo
- Medical subject headings
- Gastroenteritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | One dose of placebo on Day 1 and one dose of placebo between Day 28 and Day 56. Receives: Biological: Placebo |
| Experimental | Experimental | One dose of HIL-214 on Day 1 and one dose of HIL-214 between Day 28 and Day 56. Receives: Biological: HIL-214 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: The duration of the primary observation period was 6 months starting at 28 days post dose 2.
Secondary outcomes (8)
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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From Day 1 to end of the trial/early termination.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2022
- Study start28 Apr 2022
- Primary completion28 Dec 2023
- Study completion30 Sep 2024
Why it stopped: Lack of efficacy
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for GastroenteritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 3,084 participants (actual)
Sponsor and investigators
- Lead sponsor
- HilleVax
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05281094
- Sponsor's protocol ID
- NOR-212
- Status last verified
- Jul 2025
- First submitted
- 17 Feb 2022
- Last updated
- 10 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No