Safety and Immunogenicity of Norovirus GI.1/GII.4 Bivalent Virus-Like Particle (VLP) Vaccine in Children

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02153112
• Collaborator: (none)
• Enrollment: 840
• Locations: 12
• Arms: 10
• Actual Duration (Months): 35.9
• Patients Per Site: 70
• Patients Per Site Per Month: 1.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Norovirus	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	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 840 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: Jun 23, 2015
• Actual Primary Completion Date: Jun 20, 2018
• Actual Study Completion Date: Jun 20, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With a Seroresponse (Pan-Ig ELISA) in Cohort 1 [Day 57]

   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).

2. Percentage of Participants With a Seroresponse (Pan-Ig ELISA) in Cohort 2 [Day 140]

   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).

3. Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 1 [Day 1 after either of the vaccination given on Days 1, 29, 56 or 112]

   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.

4. Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 2 [Day 1 after either of the vaccination given on Days 1, 29, 56 or 112]

   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.

5. Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 3 [Day 3 after either of the vaccination given on Days 1, 29, 56 or 112]

   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.

6. Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 4 [Day 4 after either of the vaccination given on Days 1, 29, 56 or 112]

   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.

7. Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 5 [Day 5 after either of the vaccination given on Days 1, 29, 56 or 112]

   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.

8. Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 6 [Day 6 after either of the vaccination given on Days 1, 29, 56 or 112]

   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.

9. Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 7 [Day 7 after either of the vaccination given on Days 1, 29, 56 or 112]

   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.

10. Percentage of Participants With Solicited Systemic Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination [Days 1 through 7 after each vaccination given on Days 1, 29, 56 or 112]

    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.

11. Body Temperature Through Day 7 Following Either Vaccination [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]

    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.

12. Percentage of Participants With at Least One Unsolicited AE Following Either Vaccination Dose [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)]

    Unsolicited AEs are any local or systemic AEs, as defined by this study, that are not solicited.

13. Percentage of Participants With Serious Adverse Events (SAEs) [Cohort 1: Day 1 up to Day 210; Cohort 2: Day 1 up to Day 293]

    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.

Secondary Outcome Measures

1. Percentage of Participants With a Seroresponse for GI.1 Virus-Like Particle (VLP) (Pan-Ig ELISA) [Cohort 1: Day 57; Cohort 2: Day 140]

   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).

2. Percentage of Participants With a Seroresponse for GII.4 Virus-Like Particle (VLP) (Pan-Ig ELISA) [Cohort 1: Day 57; Cohort 2: Day 140]

   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).

3. 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 anti-norovirus GI.1 VLP antibody titers as measured by pan-Ig ELISA.

4. Geometric Mean Titer (GMT) of GII.4 VLP Antibody Titers (Pan-Ig ELISA) [Cohort 1: Day 57; Cohort 2: Day 140]

   Geometric mean titer (GMT) of anti-norovirus GII.4 VLP antibody titers as measured by pan-Ig ELISA.

5. Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (Pan-Ig ELISA) [Cohort 1: Day 57; Cohort 2: Day 140]

   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.

6. Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (Pan-Ig ELISA) [Cohort 1: Day 57; Cohort 2: Day 140]

   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.

7. Percentage of Participants With a 4-Fold Rise or Greater in Serum Antibody Titers for GI.1 VLP and GII.4 VLP (HBGA) [Cohort 1: Day 57; Cohort 2: Day 140]

   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.

8. Percentage of Participants With a 4-Fold Rise or Greater in Serum GI.1 VLP Antibody Titers (HBGA) [Cohort 1: Day 57; Cohort 2: Day 140]

   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.

9. Percentage of Participants With a 4-Fold Rise or Greater in Serum GII.4 VLP Antibody Titers (HBGA) [Cohort 1: Day 57; Cohort 2: Day 140]

   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.

10. Blocking Titers 50 (BT50) of Anti-Norovirus GI.1 VLP Antibody Titers (HBGA) [Cohort 1: Day 57; Cohort 2: Day 140]

    Blocking titers 50 (BT50) of anti-norovirus GI.1 VLP antibody titers as measured by HBGA binding assay.

11. Blocking Titers 50 (BT50) of Anti-Norovirus GII.4 VLP Antibody Titers (HBGA) [Cohort 1: Day 57; Cohort 2: Day 140]

    Blocking titers 50 (BT50) of anti-norovirus GII.4 VLP antibody titers as measured by HBGA binding assay.

12. Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (HBGA) [Cohort 1: Day 57; Cohort 2: Day 140]

    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.

13. Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (HBGA) [Cohort 1: Day 57; Cohort 2: Day 140]

    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.

14. Percentage of Participants With Any Adverse Event (AE) Leading to Withdrawal From the Study [Cohort 1: Day 1 up to Day 210; Cohort 2: Day 1 up to Day 293]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Weeks to 8 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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:

7. 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).

8. 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).

9. 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.

10. Receipt of immunostimulants within 60 days prior to Day 1.

11. 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.

12. Receipt of immunosuppressive therapy within 6 months prior to Day 1.

13. Human immunodeficiency virus (HIV) infection or HIV-related disease.

14. Chronic Hepatitis B or C infection.

15. Heritable immunodeficiency.

16. Abnormalities of splenic or thymic function.

17. Has a known bleeding diathesis or any condition that may be associated with a prolonged bleeding time.

18. Has any serious chronic or progressive disease according to judgment of the investigator (e.g., neoplasm, insulin dependent diabetes, cardiac, renal, or hepatic disease).

19. 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.

20. Has received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this trial.

21. Are first degree relatives of individuals involved in trial conduct.

22. Has a history of autoimmune disease.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centro de Estudios em Infectologia Pediatrica SAS	Cali	San Fernando	Colombia
2	Espoon Rokotetutkimusklinikka	Espoo		Finland	2230
3	Etela-Helsingin Rokotetutkimusklinikka	Helsinki		Finland	00100
4	Ita-Helsingin Rokotetutkimusklinikka	Helsinki		Finland	90220
5	Jarvenpaan Rokotetutkimusklinikka	Jarvenpaan		Finland	04400
6	Oulun Rokotetutkimusklinikka	Oulu		Finland	33100
7	Porin Rokotetutkimusklinikka	Pori		Finland	28100
8	Seinajoen Rokotetutkimusklinikka	Seinajoki		Finland	60100
9	Tampere Vaccine Research Clinic	Tampere		Finland	33100
10	Turun Rokotetutkimusklinikka	Turku		Finland	20520
11	CEVAXIN Plaza Carolina - Ciudad de Panama	Ciudad de Panama		Panama
12	CEVAXIN	Panama		Panama

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director Clinical Science, Takeda

Study Documents (Full-Text)

• Study Protocol - Mar 1, 2016
• Statistical Analysis Plan - Feb 17, 2017

More Information

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT02153112
• Other Study ID Numbers: NOR-202; 2014-000778-20; U1111-1154-9733
• First Posted: Jun 2, 2014
• Last Update Posted: Apr 1, 2019
• Last Verified: Dec 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Takeda: Drug therapy

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 12 investigative sites in Finland, Panama, and Colombia from 23 June 2015 to 20 June 2018.
Pre-assignment Detail	Healthy volunteers (children, toddlers and infants) were enrolled to receive either one, two or three doses of 4 formulation of norovirus GI.1/GII4 bivalent virus like particle (VLP) vaccine.

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Period Title: Overall Study
STARTED	61	59	61	59	60	60	60	60	180	180
COMPLETED	57	57	58	57	57	58	52	58	165	166
NOT COMPLETED	4	2	3	2	3	2	8	2	15	14

Baseline Characteristics

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses	Total
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.	Total of all reporting groups
Overall Participants	54	54	55	57	52	56	52	56	144	162	742
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	5.9	5.8	2.1	2.1	1.9	2.1	8.3	7.9	3.1	3.0	4.22
Age, Customized (Count of Participants)
Infants and Toddlers (28 days-23 months)	0 0%	0 0%	17 30.9%	19 33.3%	15 28.8%	14 25%	52 100%	56 100%	144 100%	162 100%	479 64.6%
Children (2-11 years)	54 100%	54 100%	38 69.1%	38 66.7%	37 71.2%	42 75%	0 0%	0 0%	0 0%	0 0%	263 35.4%
Sex: Female, Male (Count of Participants)
Female	32 59.3%	24 44.4%	27 49.1%	25 43.9%	28 53.8%	19 33.9%	24 46.2%	27 48.2%	77 53.5%	72 44.4%	355 47.8%
Male	22 40.7%	30 55.6%	28 50.9%	32 56.1%	24 46.2%	37 66.1%	28 53.8%	29 51.8%	67 46.5%	90 55.6%	387 52.2%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	26 48.1%	24 44.4%	26 47.3%	29 50.9%	52 100%	56 100%	52 100%	56 100%	144 100%	162 100%	627 84.5%
Not Hispanic or Latino	28 51.9%	30 55.6%	28 50.9%	27 47.4%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	113 15.2%
Not Reported	0 0%	0 0%	1 1.8%	1 1.8%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	2 0.3%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	18 33.3%	19 35.2%	9 16.4%	9 15.8%	11 21.2%	10 17.9%	24 46.2%	29 51.8%	69 47.9%	75 46.3%	273 36.8%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.9%	0 0%	0 0%	0 0%	1 0.1%
Black or African American	2 3.7%	1 1.9%	0 0%	0 0%	8 15.4%	10 17.9%	7 13.5%	5 8.9%	16 11.1%	24 14.8%	73 9.8%
Native Hawaiian or Other Pacific Islanders	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	1 1.9%	0 0%	0 0%	0 0%	1 0.1%
White	28 51.9%	30 55.6%	28 50.9%	27 47.4%	0 0%	2 3.6%	2 3.8%	0 0%	1 0.7%	3 1.9%	121 16.3%
Multiracial	0 0%	0 0%	1 1.8%	1 1.8%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	2 0.3%
Other	6 11.1%	4 7.4%	17 30.9%	20 35.1%	33 63.5%	34 60.7%	17 32.7%	22 39.3%	58 40.3%	60 37%	271 36.5%
Height (cm) [Mean (Full Range) ]
Mean (Full Range) [cm]	117.4	116.5	89.9	89.8	89.7	89.9	70.6	69.3	60.2	60.2	85.35
Weight (kg) [Mean (Full Range) ]
Mean (Full Range) [kg]	22.41	22.19	13.55	13.39	13.19	13.11	9.02	8.85	6.33	6.35	12.839

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Seroresponse (Pan-Ig ELISA) in Cohort 1
Description	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).
Time Frame	Day 57

Outcome Measure Data

Analysis Population Description

Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.
Measure Participants	53	52	51	56	47	54	49	55
Number (95% Confidence Interval) [percentage of participants]	77.4 143.3%	63.5 117.6%	74.5 135.5%	85.7 150.4%	53.2 102.3%	70.4 125.7%	71.4 137.3%	92.7 165.5%

2. Primary Outcome

Title	Percentage of Participants With a Seroresponse (Pan-Ig ELISA) in Cohort 2
Description	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).
Time Frame	Day 140

Outcome Measure Data

Analysis Population Description

Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.
Measure Participants	131	146
Number (95% Confidence Interval) [percentage of participants]	57.3 106.1%	84.9 157.2%

3. Primary Outcome

Title	Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 1
Description	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.
Time Frame	Day 1 after either of the vaccination given on Days 1, 29, 56 or 112

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of vaccine (NoV GI.1/GII.4 bivalent VLP vaccine or control vaccine). Overall number of participants analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	61	59	61	59	60	60	60	60	180	179
Any solicited local AEs	52.5 97.2%	66.1 122.4%	34.4 62.5%	45.8 80.4%	26.7 51.3%	30.0 53.6%	11.7 22.5%	13.3 23.8%	22.2 15.4%	30.7 19%
Pain	52.5 97.2%	66.1 122.4%	34.4 62.5%	35.6 62.5%	26.7 51.3%	25.0 44.6%	8.3 16%	13.3 23.8%	22.2 15.4%	28.5 17.6%
Erythema	0 0%	1.7 3.1%	1.6 2.9%	0 0%	0 0%	1.7 3%	3.3 6.3%	0 0%	1.1 0.8%	2.8 1.7%
Induration	1.6 3%	1.7 3.1%	0 0%	1.7 3%	0 0%	1.7 3%	1.7 3.3%	0 0%	0 0%	0 0%
Swelling	0 0%	5.1 9.4%	0 0%	0 0%	0 0%	1.7 3%	0 0%	0 0%	0.6 0.4%	0 0%

4. Primary Outcome

Title	Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 2
Description	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.
Time Frame	Day 1 after either of the vaccination given on Days 1, 29, 56 or 112

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of vaccine (NoV GI.1/GII.4 bivalent VLP vaccine or control vaccine). Overall number of participants analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	60	58	61	59	60	60	58	59	176	178
Any solicited local AEs	41.0 75.9%	44.1 81.7%	8.2 14.9%	25.4 44.6%	13.3 25.6%	15.0 26.8%	10.0 19.2%	5.0 8.9%	13.3 9.2%	14.5 9%
Pain	41.7 77.2%	44.8 83%	6.6 12%	23.7 41.6%	13.3 25.6%	13.3 23.8%	6.9 13.3%	5.1 9.1%	13.6 9.4%	14.6 9%
Erythema	0 0%	0 0%	3.3 6%	5.1 8.9%	0 0%	0 0%	1.7 3.3%	0 0%	0.6 0.4%	0 0%
Induration	0 0%	0 0%	0 0%	1.7 3%	0 0%	1.7 3%	0 0%	0 0%	0 0%	0 0%
Swelling	0 0%	0 0%	0 0%	1.7 3%	0 0%	1.7 3%	1.7 3.3%	0 0%	0.6 0.4%	0 0%

5. Primary Outcome

Title	Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 3
Description	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.
Time Frame	Day 3 after either of the vaccination given on Days 1, 29, 56 or 112

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of vaccine (NoV GI.1/GII.4 bivalent VLP vaccine or control vaccine). Overall number of participants analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	60	58	61	59	60	60	58	59	176	178
Any solicited local AEs	13.1 24.3%	15.3 28.3%	4.9 8.9%	20.3 35.6%	10.0 19.2%	10.0 17.9%	5.0 9.6%	6.7 12%	2.2 1.5%	5.0 3.1%
Pain	13.3 24.6%	15.5 28.7%	4.9 8.9%	20.3 35.6%	10.0 19.2%	8.3 14.8%	3.4 6.5%	6.8 12.1%	2.3 1.6%	5.1 3.1%
Erythema	0 0%	0 0%	1.6 2.9%	3.4 6%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Induration	0 0%	0 0%	1.6 2.9%	0 0%	0 0%	1.7 3%	0 0%	0 0%	0 0%	0 0%
Swelling	0 0%	0 0%	1.6 2.9%	3.4 6%	0 0%	1.7 3%	1.7 3.3%	0 0%	0 0%	0 0%

6. Primary Outcome

Title	Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 4
Description	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.
Time Frame	Day 4 after either of the vaccination given on Days 1, 29, 56 or 112

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of vaccine (NoV GI.1/GII.4 bivalent VLP vaccine or control vaccine). Overall number of participants analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	60	58	61	59	60	60	58	59	176	178
Any solicited local AEs	6.6 12.2%	6.8 12.6%	1.6 2.9%	11.9 20.9%	6.7 12.9%	10.0 17.9%	6.7 12.9%	6.7 12%	3.3 2.3%	4.5 2.8%
Pain	6.7 12.4%	6.9 12.8%	0 0%	11.9 20.9%	6.7 12.9%	6.7 12%	5.2 10%	6.8 12.1%	3.4 2.4%	4.5 2.8%
Erythema	0 0%	0 0%	1.6 2.9%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Induration	0 0%	0 0%	1.6 2.9%	1.7 3%	0 0%	1.7 3%	1.7 3.3%	0 0%	0 0%	0 0%
Swelling	0 0%	0 0%	0 0%	0 0%	0 0%	1.7 3%	0 0%	0 0%	0 0%	0 0%

7. Primary Outcome

Title	Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 5
Description	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.
Time Frame	Day 5 after either of the vaccination given on Days 1, 29, 56 or 112

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of vaccine (NoV GI.1/GII.4 bivalent VLP vaccine or control vaccine). Overall number of participants analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	60	58	61	59	60	60	58	59	176	178
Any solicited local AEs	0 0%	5.1 9.4%	1.6 2.9%	5.1 8.9%	3.3 6.3%	1.7 3%	3.3 6.3%	8.3 14.8%	1.7 1.2%	2.8 1.7%
Pain	0 0%	5.2 9.6%	0 0%	5.1 8.9%	3.3 6.3%	1.7 3%	3.4 6.5%	8.5 15.2%	1.7 1.2%	2.8 1.7%
Erythema	0 0%	0 0%	1.6 2.9%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Induration	0 0%	0 0%	1.6 2.9%	1.7 3%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Swelling	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

8. Primary Outcome

Title	Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 6
Description	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.
Time Frame	Day 6 after either of the vaccination given on Days 1, 29, 56 or 112

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of vaccine (NoV GI.1/GII.4 bivalent VLP vaccine or control vaccine). Overall number of participants analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	60	58	61	59	60	60	58	59	176	179
Any solicited local AEs	3.3 6.1%	3.4 6.3%	0 0%	3.4 6%	1.7 3.3%	1.7 3%	1.7 3.3%	5.0 8.9%	1.1 0.8%	4.5 2.8%
Pain	3.3 6.1%	3.4 6.3%	0 0%	3.4 6%	1.7 3.3%	1.7 3%	1.7 3.3%	5.1 9.1%	0.6 0.4%	4.5 2.8%
Erythema	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Induration	0 0%	0 0%	0 0%	1.7 3%	0 0%	0 0%	0 0%	1.7 3%	0 0%	0 0%
Swelling	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

9. Primary Outcome

Title	Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination on Day 7
Description	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.
Time Frame	Day 7 after either of the vaccination given on Days 1, 29, 56 or 112

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of vaccine (NoV GI.1/GII.4 bivalent VLP vaccine or control vaccine). Overall number of participants analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	60	58	61	59	60	60	58	59	176	178
Any solicited local AEs	1.6 3%	3.4 6.3%	0 0%	1.7 3%	1.7 3.3%	1.7 3%	1.7 3.3%	3.3 5.9%	0.6 0.4%	2.2 1.4%
Pain	1.7 3.1%	3.4 6.3%	0 0%	1.7 3%	1.7 3.3%	1.7 3%	1.7 3.3%	3.4 6.1%	0.6 0.4%	2.2 1.4%
Erythema	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Induration	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Swelling	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

10. Primary Outcome

Title	Percentage of Participants With Solicited Systemic Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination
Description	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.
Time Frame	Days 1 through 7 after each vaccination given on Days 1, 29, 56 or 112

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of vaccine (NoV GI.1/GII.4 bivalent VLP vaccine or control vaccine).

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	61	59	61	59	60	60	60	60	180	179
Any solicited systemic AEs	50.8 94.1%	61.0 113%	44.3 80.5%	54.2 95.1%	41.7 80.2%	43.3 77.3%	56.7 109%	50.0 89.3%	60.0 41.7%	59.2 36.5%
Headache	21.7 40.2%	25.9 48%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Fatigue	23.3 43.1%	29.3 54.3%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Myalgia	26.7 49.4%	24.1 44.6%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Arthralgia	1.7 3.1%	6.9 12.8%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
Vomiting	8.3 15.4%	5.2 9.6%	6.6 12%	6.8 11.9%	10.0 19.2%	11.7 20.9%	27.6 53.1%	16.9 30.2%	21.6 15%	23.6 14.6%
Diarrhea	6.9 12.8%	10.7 19.8%	13.1 23.8%	23.7 41.6%	18.3 35.2%	18.3 32.7%	31.0 59.6%	25.4 45.4%	31.8 22.1%	30.9 19.1%
Irritability/Fussiness	0 0%	0 0%	23.0 41.8%	30.5 53.5%	23.3 44.8%	18.3 32.7%	27.6 53.1%	23.7 42.3%	40.3 28%	41.6 25.7%
Drowsiness	0 0%	0 0%	16.4 29.8%	22.0 38.6%	23.3 44.8%	21.7 38.8%	22.4 43.1%	20.3 36.3%	33.5 23.3%	33.1 20.4%
Loss of Appetite	0 0%	0 0%	21.3 38.7%	33.9 59.5%	16.7 32.1%	18.3 32.7%	25.9 49.8%	23.7 42.3%	22.7 15.8%	19.7 12.2%

11. Primary Outcome

Title	Body Temperature Through Day 7 Following Either Vaccination
Description	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.
Time Frame	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

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of vaccine (NoV GI.1/GII.4 bivalent VLP vaccine or control vaccine).

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	61	59	61	59	60	60	60	60	180	179
Any (temperature 38°C or higher)	2 3.7%	6 11.1%	7 12.7%	5 8.8%	6 11.5%	8 14.3%	8 15.4%	11 19.6%	26 18.1%	23 14.2%
38°C - <38.5°C	0 0%	2 3.7%	2 3.6%	3 5.3%	4 7.7%	4 7.1%	5 9.6%	4 7.1%	13 9%	11 6.8%
38.5°C - <39°C	1 1.9%	2 3.7%	3 5.5%	2 3.5%	1 1.9%	3 5.4%	3 5.8%	2 3.6%	12 8.3%	7 4.3%
39°C - <39.5°C	1 1.9%	2 3.7%	1 1.8%	0 0%	1 1.9%	1 1.8%	0 0%	3 5.4%	0 0%	3 1.9%
39.5°C - <40°C	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	2 3.6%	1 0.7%	2 1.2%
40°C or higher	0 0%	0 0%	1 1.8%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

12. Primary Outcome

Title	Percentage of Participants With at Least One Unsolicited AE Following Either Vaccination Dose
Description	Unsolicited AEs are any local or systemic AEs, as defined by this study, that are not solicited.
Time Frame	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)

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of vaccine (NoV GI.1/GII.4 bivalent VLP vaccine or control vaccine).

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	61	59	61	59	60	60	60	60	180	179
Number [percentage of participants]	55.7 103.1%	55.9 103.5%	67.2 122.2%	69.5 121.9%	55.0 105.8%	46.7 83.4%	73.3 141%	70.0 125%	77.2 53.6%	76.0 46.9%

13. Primary Outcome

Title	Percentage of Participants With Serious Adverse Events (SAEs)
Description	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.
Time Frame	Cohort 1: Day 1 up to Day 210; Cohort 2: Day 1 up to Day 293

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of vaccine (NoV GI.1/GII.4 bivalent VLP vaccine or control vaccine).

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	61	59	61	59	60	60	60	60	180	179
Number [percentage of participants]	1.6 3%	3.4 6.3%	1.6 2.9%	3.4 6%	10.0 19.2%	1.7 3%	10.0 19.2%	8.3 14.8%	9.4 6.5%	13.4 8.3%

14. Secondary Outcome

Title	Percentage of Participants With a Seroresponse for GI.1 Virus-Like Particle (VLP) (Pan-Ig ELISA)
Description	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).
Time Frame	Cohort 1: Day 57; Cohort 2: Day 140

Outcome Measure Data

Analysis Population Description

Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Here, overall number of participants analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	53	52	51	56	47	54	49	55	138	150
Number (95% Confidence Interval) [percentage of participants]	88.7 164.3%	82.7 153.1%	92.2 167.6%	92.9 163%	78.7 151.3%	94.4 168.6%	95.9 184.4%	100.0 178.6%	94.9 65.9%	98.0 60.5%

15. Secondary Outcome

Title	Percentage of Participants With a Seroresponse for GII.4 Virus-Like Particle (VLP) (Pan-Ig ELISA)
Description	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).
Time Frame	Cohort 1: Day 57; Cohort 2: Day 140

Outcome Measure Data

Analysis Population Description

Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	53	52	51	56	47	54	49	55	134	150
Number (95% Confidence Interval) [percentage of participants]	81.1 150.2%	69.2 128.1%	76.5 139.1%	87.5 153.5%	63.8 122.7%	72.2 128.9%	75.5 145.2%	92.7 165.5%	58.2 40.4%	86.0 53.1%

16. Secondary Outcome

Title	Geometric Mean Titer (GMT) of GI.1 VLP Antibody Titers (Pan-Ig ELISA)
Description	Geometric mean titer (GMT) of anti-norovirus GI.1 VLP antibody titers as measured by pan-Ig ELISA.
Time Frame	Cohort 1: Day 57; Cohort 2: Day 140

Outcome Measure Data

Analysis Population Description

Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	53	52	51	56	47	54	49	55	144	162
Geometric Mean (95% Confidence Interval) [titer]	6039.1	12907.6	2856.2	7350.8	3892.1	12623.8	1240.1	7139.1	4121.1	11806.3

17. Secondary Outcome

Title	Geometric Mean Titer (GMT) of GII.4 VLP Antibody Titers (Pan-Ig ELISA)
Description	Geometric mean titer (GMT) of anti-norovirus GII.4 VLP antibody titers as measured by pan-Ig ELISA.
Time Frame	Cohort 1: Day 57; Cohort 2: Day 140

Outcome Measure Data

Analysis Population Description

Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	53	52	51	56	47	54	49	55	143	162
Geometric Mean (95% Confidence Interval) [titer]	11057.9	10228.3	3293.0	7955.2	5950.6	10896.5	620.2	3252.1	1316.2	3829.8

18. Secondary Outcome

Title	Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (Pan-Ig ELISA)
Description	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.
Time Frame	Cohort 1: Day 57; Cohort 2: Day 140

Outcome Measure Data

Analysis Population Description

Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	53	52	51	56	47	54	49	55	138	150
Geometric Mean (95% Confidence Interval) [ratio]	19.22	43.55	44.11	89.95	13.01	43.99	47.45	276.41	34.11	122.80

19. Secondary Outcome

Title	Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (Pan-Ig ELISA)
Description	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.
Time Frame	Cohort 1: Day 57; Cohort 2: Day 140

Outcome Measure Data

Analysis Population Description

Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	53	52	51	56	47	54	49	55	134	150
Number (95% Confidence Interval) [ratio]	7.46	10.00	10.87	19.20	5.62	11.93	9.54	55.73	7.85	23.55

20. Secondary Outcome

Title	Percentage of Participants With a 4-Fold Rise or Greater in Serum Antibody Titers for GI.1 VLP and GII.4 VLP (HBGA)
Description	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.
Time Frame	Cohort 1: Day 57; Cohort 2: Day 140

Outcome Measure Data

Analysis Population Description

Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	48	47	44	49	43	47	30	41	129	144
Number (95% Confidence Interval) [percentage of participants]	75.0 138.9%	91.5 169.4%	50.0 90.9%	95.9 168.2%	51.2 98.5%	89.4 159.6%	36.7 70.6%	85.4 152.5%	48.1 33.4%	67.4 41.6%

21. Secondary Outcome

Title	Percentage of Participants With a 4-Fold Rise or Greater in Serum GI.1 VLP Antibody Titers (HBGA)
Description	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.
Time Frame	Cohort 1: Day 57; Cohort 2: Day 140

Outcome Measure Data

Analysis Population Description

Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	52	50	49	53	43	50	40	50	137	157
Number (95% Confidence Interval) [percentage of participants]	94.2 174.4%	98.0 181.5%	81.6 148.4%	100.0 175.4%	74.4 143.1%	98.0 175%	50.0 96.2%	96.0 171.4%	92.0 63.9%	94.9 58.6%

22. Secondary Outcome

Title	Percentage of Participants With a 4-Fold Rise or Greater in Serum GII.4 VLP Antibody Titers (HBGA)
Description	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.
Time Frame	Cohort 1: Day 57; Cohort 2: Day 140

Outcome Measure Data

Analysis Population Description

Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	49	48	45	49	47	51	38	46	134	147
Number (95% Confidence Interval) [percentage of participants]	81.6 151.1%	93.8 173.7%	64.4 117.1%	95.9 168.2%	68.1 131%	90.2 161.1%	47.4 91.2%	87.0 155.4%	48.5 33.7%	70.7 43.6%

23. Secondary Outcome

Title	Blocking Titers 50 (BT50) of Anti-Norovirus GI.1 VLP Antibody Titers (HBGA)
Description	Blocking titers 50 (BT50) of anti-norovirus GI.1 VLP antibody titers as measured by HBGA binding assay.
Time Frame	Cohort 1: Day 57; Cohort 2: Day 140

Outcome Measure Data

Analysis Population Description

Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	52	51	49	53	45	53	42	52	142	162
Geometric Mean (95% Confidence Interval) [titer]	166.4	491.4	135.2	346.0	145.0	531.1	63.1	350.1	202.2	561.7

24. Secondary Outcome

Title	Blocking Titers 50 (BT50) of Anti-Norovirus GII.4 VLP Antibody Titers (HBGA)
Description	Blocking titers 50 (BT50) of anti-norovirus GII.4 VLP antibody titers as measured by HBGA binding assay.
Time Frame	Cohort 1: Day 57; Cohort 2: Day 140

Outcome Measure Data

Analysis Population Description

Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	50	49	46	51	47	54	43	51	136	150
Geometric Mean (95% Confidence Interval) [titer]	982.1	933.6	197.1	514.8	444.6	721.8	68.5	282.6	102.4	243.9

25. Secondary Outcome

Title	Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (HBGA)
Description	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.
Time Frame	Cohort 1: Day 57; Cohort 2: Day 140

Outcome Measure Data

Analysis Population Description

Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	52	50	49	53	43	50	40	50	137	157
Geometric Mean (95% Confidence Interval) [ratio]	8.93	23.07	7.22	22.15	6.10	24.21	3.68	20.01	11.48	32.03

26. Secondary Outcome

Title	Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (HBGA)
Description	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.
Time Frame	Cohort 1: Day 57; Cohort 2: Day 140

Outcome Measure Data

Analysis Population Description

Per-protocol set included all participants who received the planned vaccination and do not have major protocol violations. Overall number of participants analyzed is the number of participants with data available at the given time point.

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	49	48	45	49	47	51	38	46	134	147
Geometric Mean (95% Confidence Interval) [ratio]	9.31	12.73	5.35	15.95	8.34	15.36	3.91	17.00	3.73	8.13

27. Secondary Outcome

Title	Percentage of Participants With Any Adverse Event (AE) Leading to Withdrawal From the Study
Description	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.
Time Frame	Cohort 1: Day 1 up to Day 210; Cohort 2: Day 1 up to Day 293

Outcome Measure Data

Analysis Population Description

Safety analysis set included all participants who received at least 1 dose of vaccine (NoV GI.1/GII.4 bivalent VLP vaccine or control vaccine).

Arm/Group Title	Cohort 1, Group 1: 1 Dose	Cohort 1, Group 1: 2 Doses	Cohort 1, Group 2: 1 Dose	Cohort 1, Group 2: 2 Doses	Cohort 1, Group 2a: 1 Dose	Cohort 1, Group 2a: 2 Doses	Cohort 1, Group 3: 1 Dose	Cohort 1, Group 3: 2 Doses	Cohort 2, Group 4: 2 Doses	Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.	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.	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.	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.	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.	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.	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.	Toddlers 6 months to <1 year of age received 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.	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.	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.
Measure Participants	61	59	61	59	60	60	60	60	180	179
Number [percentage of participants]	0 0%	0 0%	1.6 2.9%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%

Adverse Events

Time Frame	Unsolicited AEs 28 days after each vaccination and Serious Adverse Events (SAEs) and AEs leading to trial withdrawal throughout the trial (Up to Day 210 for Cohort 1 and Day 293 for Cohort 2)
Adverse Event Reporting Description	At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Arm/Group Title	Cohort 1, Group 1: 1 Dose		Cohort 1, Group 1: 2 Doses		Cohort 1, Group 2: 1 Dose		Cohort 1, Group 2: 2 Doses		Cohort 1, Group 2a: 1 Dose		Cohort 1, Group 2a: 2 Doses		Cohort 1, Group 3: 1 Dose		Cohort 1, Group 3: 2 Doses		Cohort 2, Group 4: 2 Doses		Cohort 2, Group 4: 3 Doses
Arm/Group Description	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.		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.		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.		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.		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.		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.		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.		Toddlers 6 months to <1 year of age received 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.		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.		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.
All Cause Mortality
	Cohort 1, Group 1: 1 Dose		Cohort 1, Group 1: 2 Doses		Cohort 1, Group 2: 1 Dose		Cohort 1, Group 2: 2 Doses		Cohort 1, Group 2a: 1 Dose		Cohort 1, Group 2a: 2 Doses		Cohort 1, Group 3: 1 Dose		Cohort 1, Group 3: 2 Doses		Cohort 2, Group 4: 2 Doses		Cohort 2, Group 4: 3 Doses
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/180 (0%)		0/179 (0%)
Serious Adverse Events
	Cohort 1, Group 1: 1 Dose		Cohort 1, Group 1: 2 Doses		Cohort 1, Group 2: 1 Dose		Cohort 1, Group 2: 2 Doses		Cohort 1, Group 2a: 1 Dose		Cohort 1, Group 2a: 2 Doses		Cohort 1, Group 3: 1 Dose		Cohort 1, Group 3: 2 Doses		Cohort 2, Group 4: 2 Doses		Cohort 2, Group 4: 3 Doses
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/61 (1.6%)		2/59 (3.4%)		1/61 (1.6%)		2/59 (3.4%)		6/60 (10%)		1/60 (1.7%)		6/60 (10%)		5/60 (8.3%)		17/180 (9.4%)		24/179 (13.4%)
Blood and lymphatic system disorders
Lymphadenitis	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		1/180 (0.6%)		0/179 (0%)
Gastrointestinal disorders
Enteritis	0/61 (0%)		0/59 (0%)		0/61 (0%)		1/59 (1.7%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/180 (0%)		0/179 (0%)
Incarcerated Inguinal Hernia	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		1/60 (1.7%)		0/180 (0%)		0/179 (0%)
Intussusception	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/180 (0%)		1/179 (0.6%)
Infections and infestations
Pneumonia	1/61 (1.6%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		1/60 (1.7%)		0/60 (0%)		2/60 (3.3%)		2/60 (3.3%)		6/180 (3.3%)		9/179 (5%)
Dengue Fever	0/61 (0%)		2/59 (3.4%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/180 (0%)		0/179 (0%)
Gastroenteritis	0/61 (0%)		0/59 (0%)		1/61 (1.6%)		0/59 (0%)		0/60 (0%)		1/60 (1.7%)		1/60 (1.7%)		0/60 (0%)		2/180 (1.1%)		1/179 (0.6%)
Furuncle	0/61 (0%)		0/59 (0%)		0/61 (0%)		1/59 (1.7%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/180 (0%)		0/179 (0%)
Atypical Pneumonia	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		1/60 (1.7%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/180 (0%)		0/179 (0%)
Otitis Media Acute	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		1/60 (1.7%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/180 (0%)		0/179 (0%)
Viral Upper Respiratory Tract Infection	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		1/60 (1.7%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/180 (0%)		0/179 (0%)
Bronchiolitis	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		2/60 (3.3%)		0/60 (0%)		2/180 (1.1%)		4/179 (2.2%)
Tracheitis	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		1/60 (1.7%)		0/60 (0%)		0/180 (0%)		0/179 (0%)
Urinary Tract Infection	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		1/60 (1.7%)		0/180 (0%)		4/179 (2.2%)
Croup Infectious	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		1/180 (0.6%)		0/179 (0%)
Gastroenteritis Bacterial	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		1/180 (0.6%)		1/179 (0.6%)
Muscle Abscess	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		1/180 (0.6%)		0/179 (0%)
Subcutaneous Abscess	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		1/180 (0.6%)		2/179 (1.1%)
Pneumonia Respiratory Syncytial Viral	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/180 (0%)		2/179 (1.1%)
Bronchitis	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/180 (0%)		1/179 (0.6%)
Encephalitis	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/180 (0%)		1/179 (0.6%)
Periorbital Cellulitis	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/180 (0%)		1/179 (0.6%)
Pneumonia Bacterial	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/180 (0%)		1/179 (0.6%)
Gastroenteritis viral	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		1/60 (1.7%)		0/180 (0%)		0/179 (0%)
Injury, poisoning and procedural complications
Burns Third Degree	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		1/180 (0.6%)		0/179 (0%)
Reproductive system and breast disorders
Testicular Torsion	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		1/60 (1.7%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/180 (0%)		0/179 (0%)
Respiratory, thoracic and mediastinal disorders
Asthmatic Crisis	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		2/60 (3.3%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/180 (0%)		0/179 (0%)
Asthma	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		1/180 (0.6%)		0/179 (0%)
Other (Not Including Serious) Adverse Events
	Cohort 1, Group 1: 1 Dose		Cohort 1, Group 1: 2 Doses		Cohort 1, Group 2: 1 Dose		Cohort 1, Group 2: 2 Doses		Cohort 1, Group 2a: 1 Dose		Cohort 1, Group 2a: 2 Doses		Cohort 1, Group 3: 1 Dose		Cohort 1, Group 3: 2 Doses		Cohort 2, Group 4: 2 Doses		Cohort 2, Group 4: 3 Doses
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/61 (41%)		27/59 (45.8%)		28/61 (45.9%)		32/59 (54.2%)		21/60 (35%)		19/60 (31.7%)		36/60 (60%)		35/60 (58.3%)		119/180 (66.1%)		122/179 (68.2%)
Blood and lymphatic system disorders
Anaemia	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		9/180 (5%)		3/179 (1.7%)
Gastrointestinal disorders
Abdominal Pain Upper	3/61 (4.9%)		8/59 (13.6%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/180 (0%)		0/179 (0%)
Diarrhoea	0/61 (0%)		3/59 (5.1%)		3/61 (4.9%)		3/59 (5.1%)		0/60 (0%)		0/60 (0%)		5/60 (8.3%)		2/60 (3.3%)		10/180 (5.6%)		15/179 (8.4%)
General disorders
Pyrexia	0/61 (0%)		4/59 (6.8%)		4/61 (6.6%)		3/59 (5.1%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		6/180 (3.3%)		10/179 (5.6%)
Infections and infestations
Nasopharyngitis	15/61 (24.6%)		7/59 (11.9%)		5/61 (8.2%)		8/59 (13.6%)		14/60 (23.3%)		10/60 (16.7%)		23/60 (38.3%)		24/60 (40%)		86/180 (47.8%)		92/179 (51.4%)
Upper Respiratory Tract Infection	1/61 (1.6%)		4/59 (6.8%)		8/61 (13.1%)		7/59 (11.9%)		0/60 (0%)		0/60 (0%)		4/60 (6.7%)		0/60 (0%)		0/180 (0%)		0/179 (0%)
Rhinitis	0/61 (0%)		0/59 (0%)		5/61 (8.2%)		4/59 (6.8%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/180 (0%)		0/179 (0%)
Conjunctivitis	0/61 (0%)		0/59 (0%)		4/61 (6.6%)		2/59 (3.4%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		8/180 (4.4%)		7/179 (3.9%)
Otitis Media	0/61 (0%)		0/59 (0%)		4/61 (6.6%)		5/59 (8.5%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/180 (0%)		0/179 (0%)
Gastroenteritis	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		5/60 (8.3%)		5/60 (8.3%)		2/60 (3.3%)		3/60 (5%)		15/180 (8.3%)		11/179 (6.1%)
Viral Infection	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		2/60 (3.3%)		1/60 (1.7%)		1/60 (1.7%)		5/60 (8.3%)		11/180 (6.1%)		11/179 (6.1%)
Pharyngitis	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		3/60 (5%)		0/60 (0%)		0/60 (0%)		0/180 (0%)		0/179 (0%)
Acarodermatitis	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		4/60 (6.7%)		1/60 (1.7%)		2/180 (1.1%)		5/179 (2.8%)
Pyoderma	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		3/60 (5%)		0/60 (0%)		0/180 (0%)		0/179 (0%)
Pharyngotonsillitis	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		2/60 (3.3%)		3/60 (5%)		0/180 (0%)		0/179 (0%)
Bronchiolitis	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		9/180 (5%)		7/179 (3.9%)
Nervous system disorders
Headache	2/61 (3.3%)		5/59 (8.5%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/180 (0%)		0/179 (0%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain	4/61 (6.6%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/180 (0%)		0/179 (0%)
Cough	2/61 (3.3%)		5/59 (8.5%)		4/61 (6.6%)		5/59 (8.5%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/180 (0%)		0/179 (0%)
Skin and subcutaneous tissue disorders
Dermatitis Diaper	0/61 (0%)		0/59 (0%)		0/61 (0%)		0/59 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		0/60 (0%)		11/180 (6.1%)		18/179 (10.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.