Safety and Immunogenicity of Norovirus GI.1/GII.4 Bivalent Virus-Like Particle (VLP) Vaccine in Children
A Phase II, Randomized, Double-Blind, Dosage, Safety and Immunogenicity Trial of Intramuscular Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine Combined With Aluminum Hydroxide Adjuvant in Children, Toddlers, and Infants
3 other identifiers
interventional
840
3 countries
12
Brief Summary
The purpose of this study is to select the optimal formulation of the norovirus vaccine from different concentrations of virus-like particles (VLP) combined with aluminum hydroxide for further development in children.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jun 2015
Typical duration for phase_2
12 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 29, 2014
CompletedFirst Posted
Study publicly available on registry
June 2, 2014
CompletedStudy Start
First participant enrolled
June 23, 2015
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 20, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
June 20, 2018
CompletedResults Posted
Study results publicly available
April 1, 2019
CompletedApril 1, 2019
December 1, 2018
3 years
May 29, 2014
December 20, 2018
December 21, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (13)
Percentage of Participants With a Seroresponse (Pan-Ig ELISA) in Cohort 1
Seroresponse was defined as 4-fold rise or greater at Day 57 in serum anti-norovirus antibody titers for both GI.1 virus-Like particle (VLP) and GII.4 VLP as measured by pan immunoglobulin (Pan-Ig) enzyme-linked immunosorbent assay (ELISA).
Day 57
Percentage of Participants With a Seroresponse (Pan-Ig ELISA) in Cohort 2
Seroresponse was defined as 4-fold rise or greater at Day 140 in serum anti-norovirus antibody titers for both GI.1 virus-Like particle (VLP) and GII.4 VLP as measured by pan immunoglobulin (Pan-Ig) enzyme-linked immunosorbent assay (ELISA).
Day 140
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 1
Solicited local AEs at injection site are defined as: pain, erythema, induration, and swelling that occur on the vaccination day through Day 7 after each vaccination.
Day 1 after either of the vaccination given on Days 1, 29, 56 or 112
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 2
Solicited local AEs at injection site are defined as: pain, erythema, induration, and swelling that occur on the vaccination day through Day 7 after each vaccination.
Day 1 after either of the vaccination given on Days 1, 29, 56 or 112
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 3
Solicited local AEs at injection site are defined as: pain, erythema, induration, and swelling that occur on the vaccination day through Day 7 after each vaccination.
Day 3 after either of the vaccination given on Days 1, 29, 56 or 112
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 4
Solicited local AEs at injection site are defined as: pain, erythema, induration, and swelling that occur on the vaccination day through Day 7 after each vaccination.
Day 4 after either of the vaccination given on Days 1, 29, 56 or 112
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 5
Solicited local AEs at injection site are defined as: pain, erythema, induration, and swelling that occur on the vaccination day through Day 7 after each vaccination.
Day 5 after either of the vaccination given on Days 1, 29, 56 or 112
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 6
Solicited local AEs at injection site are defined as: pain, erythema, induration, and swelling that occur on the vaccination day through Day 7 after each vaccination.
Day 6 after either of the vaccination given on Days 1, 29, 56 or 112
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 7
Solicited local AEs at injection site are defined as: pain, erythema, induration, and swelling that occur on the vaccination day through Day 7 after each vaccination.
Day 7 after either of the vaccination given on Days 1, 29, 56 or 112
Percentage of Participants With Solicited Systemic Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination
Systemic AEs are defined as headache, fatigue, myalgia, arthralgia, vomiting (number per day/intensity), and diarrhea (number per day/consistency) for children aged 4 to \<9 years; and irritability/fussiness, drowsiness, loss of appetite, vomiting (number per day/intensity), and diarrhea (number per day/consistency) for children aged 6 weeks to \<4 years on the day of vaccination and daily through Day 7 after each vaccination.
Days 1 through 7 after each vaccination given on Days 1, 29, 56 or 112
Body Temperature Through Day 7 Following Either Vaccination
Body temperature measurement was performed using the thermometer provided by the site through Day 7 after each vaccination. The highest body temperature observed each day was recorded on the Diary Card. Body temperature is categorized as 1) Any (temperature 38°C or higher), 2) 38°C - \<38.5°C, 3) 38.5°C - \<39°C, 4) 39°C - \<39.5°C, 5) 39.5°C - \<40°C, 6) 40°C or higher. Number of participants with the particular body temperature is reported within the pre-defined categories.
Post-vaccination approximately 30 minutes and 6 hours later, then daily through Day 7 after each vaccination given on Days 1, 29, 56 or 112
Percentage of Participants With at Least One Unsolicited AE Following Either Vaccination Dose
Unsolicited AEs are any local or systemic AEs, as defined by this study, that are not solicited.
Unsolicited AEs were collected within 28 days of all vaccinations (Day 1 to 57 for Cohort 1 and Day 1 to 140 for Cohort 2)
Percentage of Participants With Serious Adverse Events (SAEs)
A serious adverse event (SAE) is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above mentioned criteria.
Cohort 1: Day 1 up to Day 210; Cohort 2: Day 1 up to Day 293
Secondary Outcomes (14)
Percentage of Participants With a Seroresponse for GI.1 Virus-Like Particle (VLP) (Pan-Ig ELISA)
Cohort 1: Day 57; Cohort 2: Day 140
Percentage of Participants With a Seroresponse for GII.4 Virus-Like Particle (VLP) (Pan-Ig ELISA)
Cohort 1: Day 57; Cohort 2: Day 140
Geometric Mean Titer (GMT) of GI.1 VLP Antibody Titers (Pan-Ig ELISA)
Cohort 1: Day 57; Cohort 2: Day 140
Geometric Mean Titer (GMT) of GII.4 VLP Antibody Titers (Pan-Ig ELISA)
Cohort 1: Day 57; Cohort 2: Day 140
Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (Pan-Ig ELISA)
Cohort 1: Day 57; Cohort 2: Day 140
- +9 more secondary outcomes
Study Arms (10)
Cohort 1, Group 1: 1 Dose
EXPERIMENTALChildren 4 to \<9 years of age received one dose of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent virus-like particle (VLP) vaccine, intramuscularly (IM) and 500 µg aluminum hydroxide on Day 1, followed by placebo matching norovirus bivalent VLP vaccine IM on Day 29.
Cohort 1, Group 1: 2 Doses
EXPERIMENTALChildren 4 to \<9 years of age received 2 doses of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide IM on Days 1 and 29.
Cohort 1, Group 2: 1 Dose
EXPERIMENTALChildren 1 to \<4 years of age received one dose of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide, IM on Day 1, followed by placebo-matching norovirus bivalent VLP vaccine, IM on Day 29.
Cohort 1, Group 2: 2 Doses
EXPERIMENTALChildren 1 to \<4 years of age received 2 doses of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide, IM on Days 1 and 29.
Cohort 1, Group 2a: 1 Dose
EXPERIMENTALChildren 1 to \<4 years of age received one dose of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide, IM on Day 1, followed by placebo matching norovirus bivalent VLP vaccine, IM on Day 29.
Cohort 1, Group 2a: 2 Doses
EXPERIMENTALChildren 1 to \<4 years of age received 2 doses of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide, IM on Days 1 and 29.
Cohort 1, Group 3: 1 Dose
EXPERIMENTALToddlers 6 months to \<1 year of age received one dose of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide, IM on Day 1, followed by placebo matching norovirus bivalent VLP vaccine, IM on Day 29.
Cohort 1, Group 3: 2 Doses
EXPERIMENTALToddlers 6 months to \<1 year of age will receive 2 doses either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide, IM on Days 1 and 29.
Cohort 2, Group 4: 2 Doses
EXPERIMENTALInfants 6 weeks to \<6 months of age received 2 doses of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) formulations of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide, IM on Days 1 and 56, followed by placebo-matching norovirus bivalent VLP vaccine, IM on Day 112.
Cohort 2, Group 4: 3 Doses
EXPERIMENTALInfants 6 weeks to \<6 months of age received 3 doses of either of the 4 formulations (15 µg of GI.1 norovirus VLP and 15 µg GII.4/GI.1/GII.4 (15 μg/50 μg)/GI.1/GII.4 (50 μg/50 μg) or GI.1/GII.4 (50 μg/150 μg) of the norovirus bivalent VLP vaccine and 500 µg aluminum hydroxide, IM on Days 1, 56 and 112.
Interventions
Norovirus GI.1/GII.4 (15 μg/15 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection
Norovirus GI.1/GII.4 (15 μg/50 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection
Norovirus GI.1/GII.4 (50 μg/50 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection
Norovirus GI.1/GII.4 (50 μg/150 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection
Placebo saline solution
Eligibility Criteria
You may qualify if:
- Male and female participants aged between 6 weeks and less than 9 years at the time of enrollment.
- 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.
- Participants legally authorized representative (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. An assent will also be obtained according to age-appropriate country-specific regulations.
- Participants who can comply with trial procedures and are available for the duration of the trial.
You may not qualify if:
- Participants with a clinically significant active infection (as assessed by the investigator) or body temperature 38.0°C (100.4°F) or higher within 3 days of the intended date of vaccination.
- Have received antipyretic/analgesic medications within 24 hours prior to the intended vaccine administration.
- Known hypersensitivity or allergy to investigational vaccine (including excipients of the investigational vaccines).
- Participants with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the ability to participate in the trial.
- Has a history of any progressive or severe neurologic disorder, seizure disorder, or neuroinflammatory disease (eg, Guillain-Barré syndrome).
- Known or suspected impairment/alteration of immune function, including the following:
- Children \<18 months of age with history of repeated episodes of acute otitis media (AOM) in the first 6 months of life (AOM defined as a bulging tympanic membrane) and not to be confused with otitis media with effusion (OME).
- Chronic use of oral steroids (equivalent to 20 mg/day prednisone for ≥12 weeks/≥2 mg/kg body weight/day for ≥2 weeks) within 60 days prior to Day 1 (use of inhaled, intranasal, or topical corticosteroids is allowed).
- Receipt of parenteral steroids (equivalent to 20 mg/day prednisone ≥12 weeks/≥2 mg/kg body weight/day for ≥2 weeks) within 60 days prior to Day 1.
- Receipt of immunostimulants within 60 days prior to Day 1.
- Receipt of parenteral, epidural, or intra-articular immunoglobulin preparation, blood products, and/or plasma derivatives within 3 months prior to Day 1 or planned during the full length of the trial.
- Receipt of immunosuppressive therapy within 6 months prior to Day 1.
- Human immunodeficiency virus (HIV) infection or HIV-related disease.
- Chronic Hepatitis B or C infection.
- Heritable immunodeficiency.
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Takedalead
Study Sites (12)
Centro de Estudios em Infectologia Pediatrica SAS
Cali, San Fernando, Colombia
Espoon Rokotetutkimusklinikka
Espoo, 2230, Finland
Etela-Helsingin Rokotetutkimusklinikka
Helsinki, 00100, Finland
Ita-Helsingin Rokotetutkimusklinikka
Helsinki, 90220, Finland
Jarvenpaan Rokotetutkimusklinikka
Jarvenpaan, 04400, Finland
Oulun Rokotetutkimusklinikka
Oulu, 33100, Finland
Porin Rokotetutkimusklinikka
Pori, 28100, Finland
Seinajoen Rokotetutkimusklinikka
Seinäjoki, 60100, Finland
Tampere Vaccine Research Clinic
Tampere, 33100, Finland
Turun Rokotetutkimusklinikka
Turku, 20520, Finland
CEVAXIN Plaza Carolina - Ciudad de Panama
Panama City, Panama
CEVAXIN
Panama City, Panama
Related Publications (1)
Lopez P, Lopez-Medina E, Saez-Llorens X, deAntonio R, Masuda T, Mendelman PM, Sherwood J, Baehner F, Borkowski A. Immunogenicity and tolerability of a bivalent virus-like particle norovirus vaccine candidate in children from 6 months up to 4 years of age: A phase 2 randomized, double-blind trial. Hum Vaccin Immunother. 2023 Dec 31;19(1):2204787. doi: 10.1080/21645515.2023.2204787. Epub 2023 May 4.
PMID: 37140558DERIVED
Results Point of Contact
- Title
- Medical Director
- Organization
- Takeda
Study Officials
- STUDY DIRECTOR
Medical Director Clinical Science
Takeda
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- PREVENTION
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 29, 2014
First Posted
June 2, 2014
Study Start
June 23, 2015
Primary Completion
June 20, 2018
Study Completion
June 20, 2018
Last Updated
April 1, 2019
Results First Posted
April 1, 2019
Record last verified: 2018-12
Data Sharing
- IPD Sharing
- Will share
Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.