Gastroenteritis
Conditions
Brief 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. The second dose of study vaccine will be given 28 days after the first dose.
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.
Interventions
BIOLOGICALHIL-214
2 injections - given on Day 1 and the second given between Day 29 - Day 57
BIOLOGICALPlacebo
2 injections - given on Day 1 and the second given between Day 29 - Day 57
Sponsors
HilleVax
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
5 Months to 5 Months
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To Demonstrate the Efficacy of HIL-214 Vaccine Against Moderate/Severe Acute Gastroenteritis (AGE) Associated Only With GI.1 or GII.4 Norovirus Genotypes. | The duration of the primary observation period was 6 months starting at 28 days post dose 2. | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | The duration of the primary observation period was 6 months starting at 28 days post dose 2. | 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. |
| 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 | The duration of the primary observation period was 6 months starting at 28 days post dose 2. | 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. |
| Immunogenicity of HIL-214 Compared to Placebo | Participant reaches 1 year of age | 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 |
| To Evaluate the Efficacy of HIL-214 Vaccine Against Moderate/Severe Acute Gastroenteritis (AGE) Associated Only With Any Norovirus (GI or GII) Genogroup. | The duration of the primary observation period was 6 months starting at 28 days post dose 2. | 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. |
| Safety of HIL-214 Compared to Placebo - Solicited Systemic Adverse Events (AEs) | Up to 7 days after each dose of HIL-214 or placebo. | 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. |
| Safety of HIL-214 Compared to Placebo - Adverse Events (AEs) Leading to Vaccine Withdrawal | Up to 28 days after first dose of HIL-214 or placebo. | Percentage of participants with AEs leading to trial vaccine dose withdrawal. |
| Safety of HIL-214 Compared to Placebo - Adverse Events (AEs) Leading to Trial Withdrawal. | From Day 1 to end of the trial/early termination. | Percentage of participants with AEs leading to trial withdrawal. |
| Safety of HIL-214 Compared to Placebo - Solicited Local Adverse Events (AEs) | Up to 7 days after each dose of HIL-214 or placebo. | 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. |
Countries
Colombia, Dominican Republic, Honduras, Panama, Peru, Puerto Rico, United States
Participant flow
Recruitment details
Participants took part in the primary observation period of the trial (up to Visit 4) at 17 investigative sites in Panama, the Dominican Republic, Honduras, Peru, Columbia, Puerto Rico, and the United States from 28 April 2022 to 28 Dec 2023.
Pre-assignment details
Participants were enrolled in 1 of 2 treatment arms and received 2 doses of either HIL-214, a norovirus vaccine comprising 50 µg GI.1 virus-like particle (VLP) and 150 µg GII.4c VLP, adjuvanted with 500 µg of aluminum hydroxide, or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Placebo One dose of placebo on Day 1 and one dose of placebo between Day 28 and Day 56. | 1,399 |
| Experimental One dose of HIL-214 on Day 1 and one dose of HIL-214 between Day 28 and Day 56. | 1,425 |
| Total | 2,824 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 1 | 2 |
| Overall Study | Lost to Follow-up | 29 | 22 |
| Overall Study | Not pre-specified reason | 8 | 5 |
| Overall Study | Withdrawal by Legally Authorized Representative | 122 | 103 |
Baseline characteristics
| Characteristic | Experimental | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 4.95 months STANDARD_DEVIATION 0.291 | 4.95 months STANDARD_DEVIATION 0.293 | 4.94 months STANDARD_DEVIATION 0.295 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1407 Participants | 2790 Participants | 1383 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 8 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 13 Participants | 26 Participants | 13 Participants |
| Head circumference | 42.06 cm STANDARD_DEVIATION 1.292 | 42.07 cm STANDARD_DEVIATION 1.304 | 42.08 cm STANDARD_DEVIATION 1.316 |
| Length | 64.05 cm STANDARD_DEVIATION 2.731 | 64.10 cm STANDARD_DEVIATION 2.694 | 64.16 cm STANDARD_DEVIATION 2.657 |
| Race/Ethnicity, Customized Race American Indian or Alaskan Native | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Race Asian | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Black or African American | 9 Participants | 23 Participants | 14 Participants |
| Race/Ethnicity, Customized Race More than one race | 9 Participants | 20 Participants | 11 Participants |
| Race/Ethnicity, Customized Race Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race Not Reported | 64 Participants | 117 Participants | 53 Participants |
| Race/Ethnicity, Customized Race Other | 1327 Participants | 2629 Participants | 1302 Participants |
| Race/Ethnicity, Customized Race Unknown | 14 Participants | 29 Participants | 15 Participants |
| Race/Ethnicity, Customized Race White | 1 Participants | 4 Participants | 3 Participants |
| Region of Enrollment Colombia | 42 participants | 86 participants | 44 participants |
| Region of Enrollment Dominican Republic | 284 participants | 557 participants | 273 participants |
| Region of Enrollment Honduras | 233 participants | 454 participants | 221 participants |
| Region of Enrollment Panama | 769 participants | 1533 participants | 764 participants |
| Region of Enrollment Peru | 95 participants | 190 participants | 95 participants |
| Region of Enrollment Puerto Rico | 1 participants | 2 participants | 1 participants |
| Region of Enrollment United States | 1 participants | 2 participants | 1 participants |
| Sex: Female, Male Female | 725 Participants | 1448 Participants | 723 Participants |
| Sex: Female, Male Male | 700 Participants | 1376 Participants | 676 Participants |
| Weight | 7.395 kg STANDARD_DEVIATION 0.9979 | 7.409 kg STANDARD_DEVIATION 0.992 | 7.423 kg STANDARD_DEVIATION 0.9861 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 1,536 | 2 / 1,541 |
| other Total, other adverse events | 889 / 1,536 | 902 / 1,541 |
| serious Total, serious adverse events | 165 / 1,536 | 169 / 1,541 |
Outcome results
Primary
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.
Population: Modified Full-Analysis Set (mFAS): The mFAS included all participants who were randomized and received 2 doses of HIL-214 or placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | To Demonstrate the Efficacy of HIL-214 Vaccine Against Moderate/Severe Acute Gastroenteritis (AGE) Associated Only With GI.1 or GII.4 Norovirus Genotypes. | 3.07 months | Standard Deviation 2.059 |
| Experimental | To Demonstrate the Efficacy of HIL-214 Vaccine Against Moderate/Severe Acute Gastroenteritis (AGE) Associated Only With GI.1 or GII.4 Norovirus Genotypes. | 3.29 months | Standard Deviation 1.746 |
Comparison: VE is defined 100% \[1- (λV/λC)\], where λV and λC denote the hazard rates for the HIL-214 and placebo arms respectively, obtained via a stratified Cox proportional hazards model, using Efron's method for handling ties. The model includes a term for vaccine group and was stratified by country, whereby the United States, Dominican Republic, and Puerto Rico were considered one country. The 95% confidence interval as calculated by subtracting the confidence limits of hazard ratio from 1.95% CI: [-52.51, 50.35]
Secondary
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
Time frame: Participant reaches 1 year of age
Population: Full-Analysis Set, The FAS will include all subjects who are randomized and received at least 1 dose of HIL-214 or placebo.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Immunogenicity of HIL-214 Compared to Placebo | Anti-GI.1 and GII.4c HBGA-blocking seroresponse rate at Visit 2 | 0 percentage of participants |
| Placebo | Immunogenicity of HIL-214 Compared to Placebo | Anti-GI.1 HBGA-blocking seroresponse rate at Visit 2 | 0.6 percentage of participants |
| Placebo | Immunogenicity of HIL-214 Compared to Placebo | Anti-GI.1 HBGA-blocking seroresponse rate at Visit 3 | 1.4 percentage of participants |
| Placebo | Immunogenicity of HIL-214 Compared to Placebo | Anti-GI.1 HBGA-blocking seroresponse rate at Visit 4 | 1.6 percentage of participants |
| Placebo | Immunogenicity of HIL-214 Compared to Placebo | Anti-GII.4c HBGA-blocking seroresponse rate at Visit 2 | 1.3 percentage of participants |
| Placebo | Immunogenicity of HIL-214 Compared to Placebo | Anti- GII.4c HBGA-blocking seroresponse rate at Visit 3 | 2.2 percentage of participants |
| Placebo | Immunogenicity of HIL-214 Compared to Placebo | Anti- GII.4c HBGA-blocking seroresponse rate at Visit 4 | 6.2 percentage of participants |
| Placebo | Immunogenicity of HIL-214 Compared to Placebo | Anti-GI.1 and GII.4c HBGA-blocking seroresponse rate at Visit 3 | 0.3 percentage of participants |
| Placebo | Immunogenicity of HIL-214 Compared to Placebo | Anti-GI.1 and GII.4c HBGA-blocking seroresponse rate at Visit 4 | 0.2 percentage of participants |
| Placebo | Immunogenicity of HIL-214 Compared to Placebo | Anti-GI.1 pan-Ig seroresponse rate at Visit 2 | 1.3 percentage of participants |
| Placebo | Immunogenicity of HIL-214 Compared to Placebo | Anti-GI.1 pan-Ig seroresponse rate at Visit 3 | 2.4 percentage of participants |
| Placebo | Immunogenicity of HIL-214 Compared to Placebo | Anti-GI.1 pan-Ig seroresponse rate at Visit 4 | 8.7 percentage of participants |
| Placebo | Immunogenicity of HIL-214 Compared to Placebo | Anti-GII.4c pan-Ig seroresponse rate at Visit 2 | 3.3 percentage of participants |
| Placebo | Immunogenicity of HIL-214 Compared to Placebo | Anti-GII.4c pan-Ig seroresponse rate at Visit 3 | 8.1 percentage of participants |
| Placebo | Immunogenicity of HIL-214 Compared to Placebo | Anti-GII.4c pan-Ig seroresponse rate at Visit 4 | 23.6 percentage of participants |
| Placebo | Immunogenicity of HIL-214 Compared to Placebo | Anti-GI.1 and GII.4c pan-Ig seroresponse rate at Visit 2 | 0.3 percentage of participants |
| Placebo | Immunogenicity of HIL-214 Compared to Placebo | Anti-GI.1 and GII.4c pan-Ig seroresponse rate at Visit 3 | 1.0 percentage of participants |
| Placebo | Immunogenicity of HIL-214 Compared to Placebo | Anti- GI.1 and GII.4c pan-Ig seroresponse rate at Visit 4 | 4.7 percentage of participants |
| Experimental | Immunogenicity of HIL-214 Compared to Placebo | Anti-GII.4c pan-Ig seroresponse rate at Visit 3 | 83.9 percentage of participants |
| Experimental | Immunogenicity of HIL-214 Compared to Placebo | Anti-GI.1 pan-Ig seroresponse rate at Visit 2 | 84.6 percentage of participants |
| Experimental | Immunogenicity of HIL-214 Compared to Placebo | Anti-GI.1 HBGA-blocking seroresponse rate at Visit 2 | 36.8 percentage of participants |
| Experimental | Immunogenicity of HIL-214 Compared to Placebo | Anti- GI.1 and GII.4c pan-Ig seroresponse rate at Visit 4 | 74.7 percentage of participants |
| Experimental | Immunogenicity of HIL-214 Compared to Placebo | Anti-GI.1 HBGA-blocking seroresponse rate at Visit 3 | 95.5 percentage of participants |
| Experimental | Immunogenicity of HIL-214 Compared to Placebo | Anti-GI.1 pan-Ig seroresponse rate at Visit 3 | 98.9 percentage of participants |
| Experimental | Immunogenicity of HIL-214 Compared to Placebo | Anti-GI.1 HBGA-blocking seroresponse rate at Visit 4 | 86.2 percentage of participants |
| Experimental | Immunogenicity of HIL-214 Compared to Placebo | Anti-GII.4c pan-Ig seroresponse rate at Visit 4 | 75.5 percentage of participants |
| Experimental | Immunogenicity of HIL-214 Compared to Placebo | Anti-GII.4c HBGA-blocking seroresponse rate at Visit 2 | 7.4 percentage of participants |
| Experimental | Immunogenicity of HIL-214 Compared to Placebo | Anti-GI.1 pan-Ig seroresponse rate at Visit 4 | 97.1 percentage of participants |
| Experimental | Immunogenicity of HIL-214 Compared to Placebo | Anti- GII.4c HBGA-blocking seroresponse rate at Visit 3 | 43.0 percentage of participants |
| Experimental | Immunogenicity of HIL-214 Compared to Placebo | Anti-GI.1 and GII.4c pan-Ig seroresponse rate at Visit 3 | 83.5 percentage of participants |
| Experimental | Immunogenicity of HIL-214 Compared to Placebo | Anti- GII.4c HBGA-blocking seroresponse rate at Visit 4 | 25.0 percentage of participants |
| Experimental | Immunogenicity of HIL-214 Compared to Placebo | Anti-GI.1 and GII.4c HBGA-blocking seroresponse rate at Visit 2 | 4.8 percentage of participants |
| Experimental | Immunogenicity of HIL-214 Compared to Placebo | Anti-GII.4c pan-Ig seroresponse rate at Visit 2 | 37.9 percentage of participants |
| Experimental | Immunogenicity of HIL-214 Compared to Placebo | Anti-GI.1 and GII.4c HBGA-blocking seroresponse rate at Visit 3 | 42.3 percentage of participants |
| Experimental | Immunogenicity of HIL-214 Compared to Placebo | Anti-GI.1 and GII.4c pan-Ig seroresponse rate at Visit 2 | 35.9 percentage of participants |
| Experimental | Immunogenicity of HIL-214 Compared to Placebo | Anti-GI.1 and GII.4c HBGA-blocking seroresponse rate at Visit 4 | 22.9 percentage of participants |
Secondary
Safety of HIL-214 Compared to Placebo - Adverse Events (AEs) Leading to Trial Withdrawal.
Percentage of participants with AEs leading to trial withdrawal.
Time frame: From Day 1 to end of the trial/early termination.
Population: Safety Analysis Set; all participants that received at least 1 dose of HIL-214 or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Safety of HIL-214 Compared to Placebo - Adverse Events (AEs) Leading to Trial Withdrawal. | 0.1 percentage of participants |
| Experimental | Safety of HIL-214 Compared to Placebo - Adverse Events (AEs) Leading to Trial Withdrawal. | 0.1 percentage of participants |
Secondary
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.
Time frame: Up to 28 days after first dose of HIL-214 or placebo.
Population: Safety Analysis Set; all participants that received at least 1 dose of HIL 214 or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Safety of HIL-214 Compared to Placebo - Adverse Events (AEs) Leading to Vaccine Withdrawal | 0 percentage of participants |
| Experimental | Safety of HIL-214 Compared to Placebo - Adverse Events (AEs) Leading to Vaccine Withdrawal | 0.1 percentage of participants |
Secondary
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.
Time frame: Up to 7 days after each dose of HIL-214 or placebo.
Population: Safety Analysis Set, all participants who were randomized and received at least 1 dose of trial vaccine (HIL-214 or placebo).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Safety of HIL-214 Compared to Placebo - Solicited Local Adverse Events (AEs) | Injection site pain | 5.4 percentage of participants |
| Placebo | Safety of HIL-214 Compared to Placebo - Solicited Local Adverse Events (AEs) | Induration | 0 percentage of participants |
| Placebo | Safety of HIL-214 Compared to Placebo - Solicited Local Adverse Events (AEs) | Erythema | 1.8 percentage of participants |
| Placebo | Safety of HIL-214 Compared to Placebo - Solicited Local Adverse Events (AEs) | Swelling | 0.1 percentage of participants |
| Placebo | Safety of HIL-214 Compared to Placebo - Solicited Local Adverse Events (AEs) | Any solicited local AE | 6.7 percentage of participants |
| Experimental | Safety of HIL-214 Compared to Placebo - Solicited Local Adverse Events (AEs) | Swelling | 0.5 percentage of participants |
| Experimental | Safety of HIL-214 Compared to Placebo - Solicited Local Adverse Events (AEs) | Any solicited local AE | 10.4 percentage of participants |
| Experimental | Safety of HIL-214 Compared to Placebo - Solicited Local Adverse Events (AEs) | Injection site pain | 8.2 percentage of participants |
| Experimental | Safety of HIL-214 Compared to Placebo - Solicited Local Adverse Events (AEs) | Erythema | 2.0 percentage of participants |
| Experimental | Safety of HIL-214 Compared to Placebo - Solicited Local Adverse Events (AEs) | Induration | 0.7 percentage of participants |
Secondary
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.
Time frame: Up to 7 days after each dose of HIL-214 or placebo.
Population: Safety Analysis Set, all participants that received at least 1 dose of HIL-214 or placebo.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Safety of HIL-214 Compared to Placebo - Solicited Systemic Adverse Events (AEs) | Irritability/fussiness | 18.0 percentage of participants |
| Placebo | Safety of HIL-214 Compared to Placebo - Solicited Systemic Adverse Events (AEs) | Loss of appetite | 7.9 percentage of participants |
| Placebo | Safety of HIL-214 Compared to Placebo - Solicited Systemic Adverse Events (AEs) | Vomiting | 7.4 percentage of participants |
| Placebo | Safety of HIL-214 Compared to Placebo - Solicited Systemic Adverse Events (AEs) | Drowsiness | 10.7 percentage of participants |
| Placebo | Safety of HIL-214 Compared to Placebo - Solicited Systemic Adverse Events (AEs) | Diarrhea | 14.6 percentage of participants |
| Placebo | Safety of HIL-214 Compared to Placebo - Solicited Systemic Adverse Events (AEs) | Any solicited systemic AE | 35.2 percentage of participants |
| Experimental | Safety of HIL-214 Compared to Placebo - Solicited Systemic Adverse Events (AEs) | Diarrhea | 15.4 percentage of participants |
| Experimental | Safety of HIL-214 Compared to Placebo - Solicited Systemic Adverse Events (AEs) | Any solicited systemic AE | 37.7 percentage of participants |
| Experimental | Safety of HIL-214 Compared to Placebo - Solicited Systemic Adverse Events (AEs) | Drowsiness | 12.7 percentage of participants |
| Experimental | Safety of HIL-214 Compared to Placebo - Solicited Systemic Adverse Events (AEs) | Loss of appetite | 8.4 percentage of participants |
| Experimental | Safety of HIL-214 Compared to Placebo - Solicited Systemic Adverse Events (AEs) | Vomiting | 8.6 percentage of participants |
| Experimental | Safety of HIL-214 Compared to Placebo - Solicited Systemic Adverse Events (AEs) | Irritability/fussiness | 20.2 percentage of participants |
Secondary
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.
Population: Modified Full-Analysis Set (mFAS): The mFAS included all participants who were randomized and received 2 doses of HIL-214 or placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | To Evaluate the Efficacy of HIL-214 Vaccine Against Moderate/Severe Acute Gastroenteritis (AGE) Associated Only With Any Norovirus (GI or GII) Genogroup. | 3.16 months | Standard Deviation 1.886 |
| Experimental | To Evaluate the Efficacy of HIL-214 Vaccine Against Moderate/Severe Acute Gastroenteritis (AGE) Associated Only With Any Norovirus (GI or GII) Genogroup. | 3.32 months | Standard Deviation 1.519 |
Comparison: VE is defined 100% \[1- (λV/λC)\], where λV and λC denote the hazard rates for the HIL-214 and placebo arms respectively, obtained via a stratified Cox proportional hazards model, using Efron's method for handling ties. The model includes a term for vaccine group and was stratified by country, whereby the United States, Dominican Republic, and Puerto Rico were considered one country. The 95% confidence interval as calculated by subtracting the confidence limits of hazard ratio from 195% CI: [-24.52, 44.7]
Secondary
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.
Time frame: The duration of the primary observation period was 6 months starting at 28 days post dose 2.
Population: Modified Full-Analysis Set (mFAS): The mFAS included all participants who were randomized and received 2 doses of HIL-214 or placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 | 3.19 months | Standard Deviation 1.852 |
| Experimental | 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 | 3.17 months | Standard Deviation 1.541 |
Comparison: VE is defined 100% \[1- (λV/λC)\], where λV and λC denote the hazard rates for the HIL-214 and placebo arms respectively, obtained via a stratified Cox proportional hazards model, using Efron's method for handling ties. The model includes a term for vaccine group and was stratified by country, whereby the United States, Dominican Republic, and Puerto Rico were considered one country. The 95% confidence interval as calculated by subtracting the confidence limits of hazard ratio from 1.95% CI: [-45.04, 22]
Secondary
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.
Time frame: The duration of the primary observation period was 6 months starting at 28 days post dose 2.
Population: Modified Full-Analysis Set (mFAS): The mFAS included all participants who were randomized and received 2 doses of HIL-214 or placebo.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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. | 3.11 months | Standard Deviation 1.981 |
| Experimental | 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. | 3.29 months | Standard Deviation 1.628 |
Comparison: VE is defined 100% \[1- (λV/λC)\], where λV and λC denote the hazard rates for the HIL-214 and placebo arms respectively, obtained via a stratified Cox proportional hazards model, using Efron's method for handling ties. The model includes a term for vaccine group and was stratified by country, whereby the United States, Dominican Republic, and Puerto Rico were considered one country. The 95% confidence interval as calculated by subtracting the confidence limits of hazard ratio from 1.95% CI: [-34.7, 44.98]