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

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.

Study Overview

• Status: Completed
• Conditions: Norovirus
• Intervention / Treatment: Biological: GI.1/GII.4 (15/15); Biological: GI.1/GII.4 (15/50); Biological: GI.1/GII.4 (50/50); Biological: GI.1/GII.4 (50/150); Drug: Placebo

Detailed Description

The vaccine being tested in this study is called norovirus GI.1/GII.4 bivalent virus-like particle (VLP) vaccine with aluminum hydroxide. The norovirus vaccine is being tested to assess different formulations of the vaccine that will then be further developed. This study will look at the number of antibodies to norovirus formed in children, toddlers and infants who are administered different formulations of the norovirus vaccine.

The study enrolled 840 patients. Participants will be randomly assigned (by chance) to one of ten treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need).

All participants in Cohort 1 will be vaccinated on Day 1 and Day 29 of the study, and all participants in Cohort 2 will be vaccinated on Day 1, Day 56, and Day 112. All treatment groups in Cohort 1 will receive either one dose of the norovirus vaccine, or two doses. One treatment group in Cohort 2 will receive 2 doses of the norovirus vaccine, and the other group will receive 3. In order to keep the treatment undisclosed to the participant and the doctor in Cohort 1, those randomized to the one-dose groups will receive the norovirus vaccine on Day 1, followed by a dose of placebo vaccine on Day 29. In order to keep the treatment arms undisclosed to the participant and the doctor in Cohort 2, those randomized to the two-dose groups will receive the norovirus vaccine on Day 1 and Day 56, followed by a dose of placebo vaccine on Day 112. Placebo vaccine is saline solution. Participants will be asked to record any symptoms that may be related to the vaccine or the injection site in a diary card for 7 days after each vaccination.

This multi-center trial will be conducted in Finland, Panama, and Colombia. The overall time to participate in this study is up to 210 days for participants in Cohort 1 and up to 293 Days for participants in Cohort 2. Participants in Cohort 1 will make 6 visits to the clinic, and participants in Cohort 2 will make 10 visits to the clinic.

• Study Type: Interventional
• Enrollment (Actual): 840
• Phase: Phase 2

Contacts and Locations

Study Locations

• Colombia
  • San Fernando
    • Cali, San Fernando, Colombia
      • Centro de Estudios em Infectologia Pediatrica SAS
• Finland
  • Espoo, Finland, 2230
    • Espoon rokotetutkimusklinikka
  • Helsinki, Finland, 00100
    • Etelä-Helsingin rokotetutkimusklinikka
  • Helsinki, Finland, 90220
    • Itä-Helsingin rokotetutkimusklinikka
  • Jarvenpaan, Finland, 04400
    • Järvenpään Rokotetutkimusklinikka
  • Oulu, Finland, 33100
    • Oulun Rokotetutkimusklinikka
  • Pori, Finland, 28100
    • Porin Rokotetutkimusklinikka
  • Seinajoki, Finland, 60100
    • Seinäjoen rokotetutkimusklinikka
  • Tampere, Finland, 33100
    • Tampere Vaccine Research Clinic
  • Turku, Finland, 20520
    • Turun Rokotetutkimusklinikka
• Panama
  • Ciudad de Panama, Panama
    • CEVAXIN Plaza Carolina - Ciudad de Panama
  • Panama, Panama
    • CEVAXIN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 6 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female participants aged between 6 weeks and less than 9 years at the time of enrollment.
2. 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.
3. 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.
4. Participants who can comply with trial procedures and are available for the duration of the trial.

Exclusion Criteria:

1. 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.
2. Have received antipyretic/analgesic medications within 24 hours prior to the intended vaccine administration.
3. Known hypersensitivity or allergy to investigational vaccine (including excipients of the investigational vaccines).
4. 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.
5. Has a history of any progressive or severe neurologic disorder, seizure disorder, or neuroinflammatory disease (eg, Guillain-Barré syndrome).

6. Known or suspected impairment/alteration of immune function, including the following:

   1. 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).
   2. 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).
   3. 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.
   4. Receipt of immunostimulants within 60 days prior to Day 1.
   5. 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.
   6. Receipt of immunosuppressive therapy within 6 months prior to Day 1.
   7. Human immunodeficiency virus (HIV) infection or HIV-related disease.
   8. Chronic Hepatitis B or C infection.
   9. Heritable immunodeficiency.
7. Abnormalities of splenic or thymic function.
8. Has a known bleeding diathesis or any condition that may be associated with a prolonged bleeding time.
9. Has any serious chronic or progressive disease according to judgment of the investigator (e.g., neoplasm, insulin dependent diabetes, cardiac, renal, or hepatic disease).
10. Is participating in any clinical trial with another investigational product 30 days prior to first trial visit or intent to participate in another clinical trial at any time during the conduct of this trial.
11. Has received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this trial.
12. Are first degree relatives of individuals involved in trial conduct.
13. Has a history of autoimmune disease.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1, Group 1: 1 Dose; Children 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.	Biological: GI.1/GII.4 (15/15); Norovirus GI.1/GII.4 (15 μg/15 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (15/50); Norovirus GI.1/GII.4 (15 μg/50 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (50/50); Norovirus GI.1/GII.4 (50 μg/50 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (50/150); Norovirus GI.1/GII.4 (50 μg/150 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Drug: Placebo; Placebo saline solution
Experimental: Cohort 1, Group 1: 2 Doses; Children 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.	Biological: GI.1/GII.4 (15/15); Norovirus GI.1/GII.4 (15 μg/15 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (15/50); Norovirus GI.1/GII.4 (15 μg/50 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (50/50); Norovirus GI.1/GII.4 (50 μg/50 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (50/150); Norovirus GI.1/GII.4 (50 μg/150 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection
Experimental: Cohort 1, Group 2: 1 Dose; Children 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.	Biological: GI.1/GII.4 (15/15); Norovirus GI.1/GII.4 (15 μg/15 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (15/50); Norovirus GI.1/GII.4 (15 μg/50 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (50/50); Norovirus GI.1/GII.4 (50 μg/50 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (50/150); Norovirus GI.1/GII.4 (50 μg/150 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Drug: Placebo; Placebo saline solution
Experimental: Cohort 1, Group 2: 2 Doses; Children 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.	Biological: GI.1/GII.4 (15/15); Norovirus GI.1/GII.4 (15 μg/15 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (15/50); Norovirus GI.1/GII.4 (15 μg/50 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (50/50); Norovirus GI.1/GII.4 (50 μg/50 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (50/150); Norovirus GI.1/GII.4 (50 μg/150 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection
Experimental: Cohort 1, Group 2a: 1 Dose; Children 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.	Biological: GI.1/GII.4 (15/15); Norovirus GI.1/GII.4 (15 μg/15 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (15/50); Norovirus GI.1/GII.4 (15 μg/50 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (50/50); Norovirus GI.1/GII.4 (50 μg/50 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (50/150); Norovirus GI.1/GII.4 (50 μg/150 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Drug: Placebo; Placebo saline solution
Experimental: Cohort 1, Group 2a: 2 Doses; Children 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.	Biological: GI.1/GII.4 (15/15); Norovirus GI.1/GII.4 (15 μg/15 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (15/50); Norovirus GI.1/GII.4 (15 μg/50 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (50/50); Norovirus GI.1/GII.4 (50 μg/50 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (50/150); Norovirus GI.1/GII.4 (50 μg/150 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection
Experimental: Cohort 1, Group 3: 1 Dose; Toddlers 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.	Biological: GI.1/GII.4 (15/15); Norovirus GI.1/GII.4 (15 μg/15 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (15/50); Norovirus GI.1/GII.4 (15 μg/50 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (50/50); Norovirus GI.1/GII.4 (50 μg/50 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (50/150); Norovirus GI.1/GII.4 (50 μg/150 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Drug: Placebo; Placebo saline solution
Experimental: Cohort 1, Group 3: 2 Doses; Toddlers 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.	Biological: GI.1/GII.4 (15/15); Norovirus GI.1/GII.4 (15 μg/15 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (15/50); Norovirus GI.1/GII.4 (15 μg/50 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (50/50); Norovirus GI.1/GII.4 (50 μg/50 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (50/150); Norovirus GI.1/GII.4 (50 μg/150 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection
Experimental: Cohort 2, Group 4: 2 Doses; Infants 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.	Biological: GI.1/GII.4 (15/15); Norovirus GI.1/GII.4 (15 μg/15 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (15/50); Norovirus GI.1/GII.4 (15 μg/50 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (50/50); Norovirus GI.1/GII.4 (50 μg/50 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (50/150); Norovirus GI.1/GII.4 (50 μg/150 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Drug: Placebo; Placebo saline solution
Experimental: Cohort 2, Group 4: 3 Doses; Infants 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.	Biological: GI.1/GII.4 (15/15); Norovirus GI.1/GII.4 (15 μg/15 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (15/50); Norovirus GI.1/GII.4 (15 μg/50 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (50/50); Norovirus GI.1/GII.4 (50 μg/50 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection; Biological: GI.1/GII.4 (50/150); Norovirus GI.1/GII.4 (50 μg/150 μg) bivalent VLP vaccine combined with 500 μg aluminum hydroxide for IM injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Seroresponse for GI.1 Virus-Like Particle (VLP) (Pan-Ig ELISA)	Seroresponse was defined as 4-fold rise or greater in serum anti-norovirus antibody titers for GI.1 virus-Like particle (VLP) as measured by pan immunoglobulin (Pan-Ig) enzyme-linked immunosorbent assay (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)	Seroresponse was defined as 4-fold rise or greater in serum anti-norovirus antibody titers for GII.4 virus-Like particle (VLP) as measured by pan immunoglobulin (Pan-Ig) enzyme-linked immunosorbent assay (ELISA).	Cohort 1: Day 57; Cohort 2: Day 140
Geometric Mean Titer (GMT) of GI.1 VLP Antibody Titers (Pan-Ig ELISA)	Geometric mean titer (GMT) of anti-norovirus GI.1 VLP antibody titers as measured by pan-Ig ELISA.	Cohort 1: Day 57; Cohort 2: Day 140
Geometric Mean Titer (GMT) of GII.4 VLP Antibody Titers (Pan-Ig ELISA)	Geometric mean titer (GMT) of anti-norovirus GII.4 VLP antibody titers as measured by 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)	Geometric mean fold rise (GMFR) of anti-norovirus GI.1 VLP antibody titers as measured by pan-Ig ELISA. The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level.	Cohort 1: Day 57; Cohort 2: Day 140
Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (Pan-Ig ELISA)	Geometric mean fold rise (GMFR) of anti-norovirus GII.4 VLP antibody titers as measured by pan-Ig ELISA. The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level.	Cohort 1: Day 57; Cohort 2: Day 140
Percentage of Participants With a 4-Fold Rise or Greater in Serum Antibody Titers for GI.1 VLP and GII.4 VLP (HBGA)	Percentage of participants with a 4-fold rise or greater in serum anti-norovirus antibody titers for both GI.1 VLP and GII.4 VLP as measured by histoblood group antigen (HBGA) binding assay.	Cohort 1: Day 57; Cohort 2: Day 140
Percentage of Participants With a 4-Fold Rise or Greater in Serum GI.1 VLP Antibody Titers (HBGA)	The percentage of participants with a 4-fold rise or greater in serum anti-norovirus antibody titers for GI.1 virus-like particle (VLP) as measured by HBGA binding assay.	Cohort 1: Day 57; Cohort 2: Day 140
Percentage of Participants With a 4-Fold Rise or Greater in Serum GII.4 VLP Antibody Titers (HBGA)	The percentage of participants with a 4-fold rise or greater in serum anti-norovirus antibody titers for GII.4 virus-like particle (VLP) as measured by HBGA binding assay.	Cohort 1: Day 57; Cohort 2: Day 140
Blocking Titers 50 (BT50) of Anti-Norovirus GI.1 VLP Antibody Titers (HBGA)	Blocking titers 50 (BT50) of anti-norovirus GI.1 VLP antibody titers as measured by HBGA binding assay.	Cohort 1: Day 57; Cohort 2: Day 140
Blocking Titers 50 (BT50) of Anti-Norovirus GII.4 VLP Antibody Titers (HBGA)	Blocking titers 50 (BT50) of anti-norovirus GII.4 VLP antibody titers as measured by HBGA binding assay.	Cohort 1: Day 57; Cohort 2: Day 140
Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (HBGA)	Geometric mean fold rise (GMFR) of anti-norovirus GI.1 VLP antibody titers as measured by pan-Ig ELISA. The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level.	Cohort 1: Day 57; Cohort 2: Day 140
Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (HBGA)	Geometric mean fold rise (GMFR) of anti-norovirus GII.4 VLP antibody titers as measured by pan-Ig ELISA. The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level.	Cohort 1: Day 57; Cohort 2: Day 140
Percentage of Participants With Any Adverse Event (AE) Leading to Withdrawal From the Study	Withdrawal due to an AE will occur if the participant experiences an AE that requires early termination because continued participation imposes an unacceptable risk to the participant's health or the participant is unwilling to continue because of the AE.	Cohort 1: Day 1 up to Day 210; Cohort 2: Day 1 up to Day 293

Collaborators and Investigators

• Sponsor: Takeda

Study record dates

Study Major Dates

• Study Start (Actual): June 23, 2015
• Primary Completion (Actual): June 20, 2018
• Study Completion (Actual): June 20, 2018

Study Registration Dates

• First Submitted: May 29, 2014
• First Submitted That Met QC Criteria: May 29, 2014
• First Posted (Estimate): June 2, 2014

Study Record Updates

• Last Update Posted (Actual): April 1, 2019
• Last Update Submitted That Met QC Criteria: December 21, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: Drug therapy
• Other Study ID Numbers: NOR-202; 2014-000778-20 (EudraCT Number); U1111-1154-9733 (Other Identifier: World Health Organization)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: 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.

Drug and device information, study documents

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