Safety and Immunogenicity of HIL-214 With Routine Pediatric Vaccines

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

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.

Study Overview

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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 329
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Panama
  • La Chorrera, Panama
    • CEVAXIN-La Chorrera
  • Panama City, Panama
    • Cervaxin-Tocumen
  • Panamá City, Panama
    • Cervaxin-Avenida Mexico
• Puerto Rico
  • San Juan, Puerto Rico, 00907
    • BRCR Global
  • San Juan, Puerto Rico, 00936
    • HACTR
• United States
  • Louisiana
    • Lafayette, Louisiana, United States, 70508
      • Velocity Clinical Research - Lafayette
  • Montana
    • Missoula, Montana, United States, 59804
      • Boeson Research MSO
  • Nebraska
    • Hastings, Nebraska, United States, 68901
      • Velocity Clinical Research - Hastings
    • Lincoln, Nebraska, United States, 68516
      • Frontier Pediatric Care
  • Texas
    • Houston, Texas, United States, 77071
      • La Providence Pediatrics Clinic - Chemidox Clinical Trials (Hypercore)
  • Utah
    • Kaysville, Utah, United States, 84037
      • Alliance for Multispecialty Research LLC - Kaysville
    • Syracuse, Utah, United States, 84075
      • Alliance for Multispecialty Research LLC - Syracuse

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

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.

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
Experimental: Experimental; 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; 2 injections - given at 4 months and the second at 6 months of age.
Placebo Comparator: Placebo; 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; 2 injections - given at 4 months and the second at 6 months of age.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune Response to the Licensed Pediatric DTaP-Hib-IPV-HepB Vaccine 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.	Evaluate the immune response to the licensed pediatric DTaP-Hib-IPV-HepB vaccine co-administered with a 2-dose regimen of HIL-214 at 4 and 6 months of age, compared to that of the routine pediatric vaccine co-administered with placebo. Due to differing local availability of licensed DTaP-Hib-IPV-HepB vaccine, data are presented by country (Panama and USA). 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 Geometric mean (geometric mean standard deviation) anti-FHA, anti-PRN, and anti-PTX are presented as a separate outcome.	28 days post-dose 2
Immune Response to the Licensed Pediatric DTaP-Hib-IPV-HepB Vaccine 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.	Evaluate the immune response to the licensed pediatric DTaP-Hib-IPV-HepB vaccine co-administered with a 2-dose regimen of HIL-214 at 4 and 6 months of age, compared to that of the routine pediatric vaccine co-administered with placebo. Due to differing local availability of licensed DTaP-Hib-IPV-HepB vaccine, data are presented by country (Panama and USA). Outcome measures: Geometric mean anti-FHA, anti-PRN, and anti-PTX concentrations	28 days post-dose 2
Immune Response to the Licensed Pediatric Pneumococcal 13 Valent (PCV13) Vaccine 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.	The outcome was assessed using measurements of immune response to the concomitant anti-pneumococcal capsular polysaccharide IgG [serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 19A, 19F, 18C, and 23F]) at 28 days post-dose. Geometric mean concentrations are presented.	28 days post-dose 2
Immune Response to the Licensed Pediatric Rotavirus Vaccine (RV1) Vaccine 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.	This outcome was assessed using measurements of immune response to the concomitant RV1 vaccine (anti-RV1 IgA). Geometric mean concentrations at 28 days post-dose 2 are reported.	28 days post-dose 2

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity of a 2-dose Regimen of HIL-214 Co-administered With Routine Pediatric Vaccines at 4 and 6 Months of Age.	Anti-norovirus (GI.1 and GII.4c) HBGA-blocking antibodies were measured at prior to dose 1 (~4 months of age) and 28 days post-dose 2 (~6 months of age). Seroresponse was defined as a fold increase from baseline greater than or equal to 4. Seroresponse rates and 95% confidence intervals (CIs) are presented. Data are stratified by country (Panama and USA).	Pre-dose 1 and 28 days post-dose 2
Evaluate the Safety Profile of a 2-dose Regimen of HIL-214 Co-administered With Routine Pediatric Vaccines at 4 and 6 Months of Age, Compared to That of the Routine Pediatric Vaccines Co-administered With Placebo.	Percentage of participants with solicited local (injection site) reactions within 7 days of any vaccine administration. Assessed reactions included pain, redness, induration, and swelling.	Day 1 to Day 7 post-dose 1 and Day 1 to Day 7 post-dose 2
Evaluate the Safety Profile of a 2-dose Regimen of HIL-214 Co-administered With Routine Pediatric Vaccines at 4 and 6 Months of Age, Compared to That of the Routine Pediatric Vaccines Co-administered With Placebo.	Percentage of participants with solicited systemic adverse events (AEs) within 7 days of any vaccine administration. Assessed AEs included drowsiness, irritability/fussiness, loss of appetite, fever, vomiting, and diarrhea.	Day 1 to Day 7 post-dose 1 and Day 1 to Day 7 post-dose 2
Evaluate the Safety Profile of a 2-dose Regimen of HIL-214 Co-administered With Routine Pediatric Vaccines at 4 and 6 Months of Age, Compared to That of the Routine Pediatric Vaccines Co-administered With Placebo.	Percentage of participants with adverse events (AEs) leading to vaccine discontinuation or trial withdrawal.	Day 1 to 28 days post-dose 1 (vaccine discontinuation); Day 1 to 12 months post-dose 1
Evaluate the Safety Profile of a 2-dose Regimen of HIL-214 Co-administered With Routine Pediatric Vaccines at 4 and 6 Months of Age, Compared to That of the Routine Pediatric Vaccines Co-administered With Placebo	Percentage of participants with medically attended adverse events (AEs) at any point during the trial.	Day 1 to 12 months post-dose 1

Collaborators and Investigators

• Sponsor: HilleVax

Study record dates

Study Major Dates

• Study Start (Actual): June 10, 2023
• Primary Completion (Actual): January 19, 2024
• Study Completion (Actual): July 8, 2024

Study Registration Dates

• First Submitted: March 21, 2023
• First Submitted That Met QC Criteria: April 26, 2023
• First Posted (Actual): May 1, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 21, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis
• Other Study ID Numbers: NOR-206

Drug and device information, study documents

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