Safety and Immunogenicity of Norovirus Bivalent Virus-Lik... | NCT02142504

ID	Type	Description	Link
U1111-1155-8803	Other Identifier	World Health Organization

Description Module

Detailed Description

The vaccine being tested in this study is called norovirus GI.1/GII.4 bivalent virus-like particle (VLP) vaccine adjuvanted with or without monophosphoryl lipid A (MPL) and with aluminum hydroxide. The norovirus vaccine is being tested to provide additional safety and immunogenicity data to enable the vaccine to be further developed. This study will look at the side effects in people who take different formulations of the norovirus vaccine.

The study will enroll approximately 450 participants. Participants will be randomly assigned (by chance, like flipping a coin) to one of the 3 treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):

one dose of GI.1/GII.4 (15 µg/50 µg) adjuvanted with MPL (50 µg) and aluminum hydroxide (500 µg) on Day 1 followed by one dose of GI.1/GII.4 (15 µg/15 µg) adjuvanted with aluminum hydroxide (500 µg) (without MPL) on Day 365
one dose of GI.1/GII.4 (50 µg/50 µg) adjuvanted with MPL (50 µg) and aluminum hydroxide (500 µg) on Day 1 followed by one dose of GI.1/GII.4 (15 µg/15 µg) adjuvanted with aluminum hydroxide (500 µg) (without MPL) on Day 365
one dose of Saline Placebo (dummy inactive injection) - this is a liquid that has no active ingredient-on Day 1 + GI.1/GII.4 (15 µg/15 µg) adjuvanted with aluminum hydroxide (500 µg) (without MPL) as primary vaccination on Day 365

All participants will be administered vaccine or placebo on Day 1 of the study and will receive a vaccination dose (reduced antigen content) of the norovirus vaccine on Day 365. 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 the United States. The overall time to participate in this study is up to 18 months. Participants will make 11 visits to the clinic including a follow-up visit 6 months after the last dose of study medication.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	Experimental	Intramuscular (IM) norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg monophosphoryl lipid A (MPL) and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no MPL), on Day 365.	Biological: Norovirus Bivalent VLP Vaccine
GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	Experimental	IM norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg monophosphoryl lipid A (MPL) and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no MPL), on Day 365.	Biological: Norovirus Bivalent VLP Vaccine
Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Placebo Comparator	IM saline placebo on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP ) adjuvanted with 500 µg aluminum hydroxide (no MPL), on Day 365.	Biological: Norovirus Bivalent VLP Vaccine Drug: Placebo (Saline)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Norovirus Bivalent VLP Vaccine	Biological	Norovirus GI.1/GII.4 bivalent VLP vaccine adjuvanted with or without MPL and/or aluminum hydroxide IM injection	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site After the First Injection	Solicited local AEs at injection site are defined as: pain, erythema, induration, and swelling that occurred within 7 days after the primary injection.	Days 1 through 7
Percentage of Participants With Solicited Systemic Adverse Events (AEs) After the First Injection	Solicited systemic AEs are defined as: headache, fatigue, myalgia, arthralgia, vomiting, and diarrhea that occurred within 7 days after the primary injection.	Days 1 through 7
Percentage of Participants With Elevated Daily Oral Temperature (Fever) After the First Injection	Fever is defined as greater than or equal to 38°C (100.4°F). Oral body temperature measurement was performed using the thermometer provided by the site for 7 days after each injection. The highest body temperature observed each day was recorded on the Diary Card also provided by the site.	Days 1 through 7
Percentage of Participants With Unsolicited Adverse Events (AEs) After the First Injection	Unsolicited AEs are any AEs that are not solicited local or systemic AEs, as defined by this study.	Days 1 through 28
Percentage of Participants With Serious Adverse Events (SAEs) After the First Injection	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.	From first injection (Day 1) to second injection pre-dose (Up to Day 365)

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site After the Second Injection	Solicited local AEs at injection site are defined as: pain, erythema, induration, and swelling that occurred within 7 days after the vaccination on Day 365.	Days 365 through 371
Percentage of Participants With Solicited Systemic Adverse Events (AEs) After the Second Injection

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male and female participants aged 18 to 49 years of age at the time of enrollment.
Are in good health at the time of entry into the trial as determined by medical history, physical examination and clinical judgment of the investigator.
Participants with a signed informed consent form and any required privacy authorization prior to the initiation of any trial procedures and after the nature of the trial has been explained according to local regulatory requirements.
Can comply with trial procedures and are available for the duration of the trial.

Exclusion Criteria:

Has a history of acute gastroenteritis within 14 days of enrollment.
Has a clinically significant active infection (as assessed by the investigator) or oral body temperature 38°C (100.4°F) or higher within 3 days of the intended date of vaccination.
Has received antipyretic/analgesic medications within 24 hours prior to the intended vaccine administration.
Has known hypersensitivity or allergy to any of the bivalent norovirus virus-like particle (VLP) vaccine components (including excipients of the investigational vaccines).
Has behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the participant's ability to participate in the trial.
Has a history of any progressive or severe neurologic disorder, seizure disorder, or neuro-inflammatory disease (e.g., Guillain-Barré syndrome).
Has history or any illness that, in the opinion of the investigator, might interfere with the results of the trial or pose additional risk to the participants due to participation in the trial.
Has known or suspected impairment/alteration of immune function including the following:
1. 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).
2. 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.
3. Receipt of immunostimulants within 60 days prior to Day 1.
4. 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.
5. Receipt of immunosuppressive therapy within 6 months prior to Day 1.
6. Human immunodeficiency virus (HIV) infection or HIV-related disease.
7. Heritable immunodeficiency.
Has abnormalities of splenic or thymic function.
Has a history of any autoimmune disease.
Has a known bleeding diathesis or any condition that may be associated with a prolonged bleeding time.
Has any serious chronic or progressive disease according to judgment of the investigator (e.g., neoplasm, insulin dependent diabetes, cardiac, renal, or hepatic disease).
Has a body mass index (BMI) greater than or equal to 35 kg/m^2 (= weight in kg / [height in meters * height in meters]).
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.
Participants who received any inactivated vaccines within 14 days or any live vaccines for 28 days prior to enrollment in this trial.
Are first degree relatives of individuals involved in trial conduct.
Has a history of substance or alcohol abuse within the past 2 years.
If female, "of childbearing potential", sexually active, and has not used any of the "acceptable contraceptive methods" for at least 2 months prior to trial entry:
1. Of childbearing potential is defined as status post onset of menarche and not meeting any of the following conditions: menopausal for at least 2 years, status after bilateral tubal ligation for at least 1 year, status after bilateral oophorectomy, or status after hysterectomy.
2. Acceptable birth control methods are defined as 1 or more of the following:
i. Hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring).

ii. Barrier (condom with spermicide or diaphragm with spermicide) each and every time during intercourse.

iii. Intrauterine device (IUD). iv. Monogamous relationship with vasectomized partner. Partner must have been vasectomized for at least 6 months prior to the participant's trial entry.
Female participants of childbearing potential and sexually active, who refuse to use an "acceptable contraceptive method" from Day 1 through 6 months after the last dose of investigational vaccine.
Female participants who plan to donate ova from Day 1 through 6 months after the last dose of investigational vaccine.
Female participants with any positive pregnancy test.
Female participants who are pregnant or breastfeeding.

Name	Affiliation	Role
Medical Director Clinical Science	Takeda	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
California Research Foundation		San Diego	California	92103-6204	United States
Benchmark Research San Francisco

PubMed Identifier	Type	Citation	Retractions
31001633	Derived	Atmar RL, Baehner F, Cramer JP, Lloyd E, Sherwood J, Borkowski A, Mendelman PM; NOR-201 Study Group. Persistence of Antibodies to 2 Virus-Like Particle Norovirus Vaccine Candidate Formulations in Healthy Adults: 1-Year Follow-up With Memory Probe Vaccination. J Infect Dis. 2019 Jul 19;220(4):603-614. doi: 10.1093/infdis/jiz170.
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Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
FG001

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
BG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.
BG002	GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no MPL), on Day 365.
BG003	Total	Total of all reporting groups

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site After the First Injection

Solicited local AEs at injection site are defined as: pain, erythema, induration, and swelling that occurred within 7 days after the primary injection.

Safety Analysis Set included all participants who received at least one dose of trial vaccination.

Posted

Number

percentage of participants

Days 1 through 7

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.
OG002	GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no MPL), on Day 365.

Units	Counts
Participants	OG000153 OG001145 OG002154

Title

Denominators

Categories

Any Solicited Local AEs

Title	Measurements
	OG0007.8 OG00164.1 OG00272.7

Pain

Primary

Percentage of Participants With Solicited Systemic Adverse Events (AEs) After the First Injection

Solicited systemic AEs are defined as: headache, fatigue, myalgia, arthralgia, vomiting, and diarrhea that occurred within 7 days after the primary injection.

Safety Analysis Set included all participants who received at least one dose of trial vaccination.

Posted

Number

percentage of participants

Days 1 through 7

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.
OG002	GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)

Primary

Percentage of Participants With Elevated Daily Oral Temperature (Fever) After the First Injection

Fever is defined as greater than or equal to 38°C (100.4°F). Oral body temperature measurement was performed using the thermometer provided by the site for 7 days after each injection. The highest body temperature observed each day was recorded on the Diary Card also provided by the site.

Safety Analysis Set included all participants who received at least one dose of trial vaccination.

Posted

Number

percentage of participants

Days 1 through 7

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.
OG002	GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)

Primary

Percentage of Participants With Unsolicited Adverse Events (AEs) After the First Injection

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

Safety Analysis Set included all participants who received at least one dose of trial vaccination.

Posted

Number

percentage of participants

Days 1 through 28

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.
OG002	GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no MPL), on Day 365.

Primary

Percentage of Participants With Serious Adverse Events (SAEs) After the First Injection

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.

Safety Analysis Set included all participants who received at least one dose of trial vaccination.

Posted

Number

percentage of participants

From first injection (Day 1) to second injection pre-dose (Up to Day 365)

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.

Primary

Percentage of Participants With Serious Adverse Events (SAEs) After the Second Injection

Participants from the Safety Analysis Set who received a second injection.

Posted

Number

percentage of participants

From second injection (Day 365) to 6 months after second injection (Up to Day 545)

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.

Primary

Percentage of Participants With Adverse Events of Special Interest (AESI) After the First Injection

AESIs are AEs that are not solicited local or systemic AEs, they are predefined AEs that required close monitoring and prompt reporting to the sponsor. AESI included protocol specified Cardiac Disorders, Gastrointestinal Disorders, Immune System Disorders, Infections and Infestations, Musculoskeletal and Connective Tissue Diseases, Neuroinflammatory Disorders, Renal and Urinary Disorders, Skin Disorders, Thyroid Disorders, Vascular Disorders and Other Disorders.

Safety Analysis Set included all participants who received at least one dose of trial vaccination.

Posted

Number

percentage of participants

From first injection (Day 1) to second injection pre-dose (Up to Day 365)

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.

Primary

Percentage of Participants With Adverse Events of Special Interest (AESI) After the Second Injection

Participants from the Safety Analysis Set who received a second injection.

Posted

Number

percentage of participants

From second injection (Day 365) to 6 months after second injection (Up to Day 545)

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.

Primary

Percentage of Participants With Any Adverse Event (AE) Leading to Withdrawal From the Study

Withdrawal due to an AE occurred if the participant experienced an AE that required early termination because continued participation imposed an unacceptable risk to the participant's health or the participant was unwilling to continue because of the AE.

Safety Analysis Set included all participants who received at least one dose of trial vaccination.

Posted

Number

percentage of participants

Unsolicited AEs 28 days after each injection (Days 1 to 28 and Days 365 to 393), and Serious Adverse Events (SAEs) throughout the trial (Up to Day 545)

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.

Secondary

Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site After the Second Injection

Solicited local AEs at injection site are defined as: pain, erythema, induration, and swelling that occurred within 7 days after the vaccination on Day 365.

Participants from the Safety Analysis Set who received a second injection.

Posted

Number

percentage of participants

Days 365 through 371

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.
OG002	GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)

Secondary

Percentage of Participants With Solicited Systemic Adverse Events (AEs) After the Second Injection

Solicited systemic AEs are defined as: headache, fatigue, myalgia, arthralgia, vomiting, and diarrhea that occurred within 7 days after the vaccination on Day 365.

Participants from the Safety Analysis Set who received a second injection.

Posted

Number

percentage of participants

Days 365 through 371

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.
OG002	GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)

Secondary

Percentage of Participants With Elevated Daily Oral Temperature (Fever) After the Second Injection

Fever is defined as greater than or equal to 38°C (100.4°F). Oral body temperature measurement was performed using the thermometer provided by the site for 7 days after each vaccination. The highest body temperature observed each day was recorded on the Diary Card also provided by the site.

Participants from the Safety Analysis Set who received a second injection.

Posted

Number

percentage of participants

Days 365 through 371

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.
OG002	GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)

Secondary

Percentage of Participants With Unsolicited Adverse Events (AEs) After the Second Injection

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

Participants from the Safety Analysis Set who received a second injection.

Posted

Number

percentage of participants

Days 365 through 393

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.
OG002	GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no MPL), on Day 365.

Secondary

Percentage of Participants With a Seroresponse in Both Serum Anti-norovirus GI.1 VLP and GII.4 VLP (Pan-Ig ELISA)

Seroresponse is defined as 4-fold rise or greater 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).

Per Protocol Set included all participants in Full Analysis Set, who had evaluable blood samples at baseline, and Day 28 within the specified window (+/- 7 days), and did not have major protocol violations.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline and Day 28

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.

Secondary

Percentage of Participants With a Seroresponse in Serum Anti-norovirus GI.1 VLP (Pan-Ig ELISA)

Seroresponse is 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).

Posted

Number

95% Confidence Interval

percentage of participants

Baseline and Day 28

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.
OG002

Secondary

Percentage of Participants With a Seroresponse in Serum Anti-norovirus GII.4 VLP (Pan-Ig ELISA)

Seroresponse is defined as 4-fold rise or greater in serum anti-norovirus antibody titers for GII.4 virus-like particles (VLP) as measured by pan immunoglobulin (Pan-Ig) enzyme-linked immunosorbent assay (ELISA).

Posted

Number

95% Confidence Interval

percentage of participants

Baseline and Day 28

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.
OG002

Secondary

Geometric Mean Titer (GMT) of GI.1 VLP Antibody Titers (Pan-Ig ELISA)

Geometric mean titer (GMT) of anti-norovirus GI.1 VLP antibody titers as measured by Pan-Ig ELISA.

Posted

Geometric Mean

Standard Deviation

titer

Day 28

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.
OG002	GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)

Secondary

Geometric Mean Titer (GMT) of GII.4 VLP Antibody Titers (Pan-Ig ELISA)

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

Posted

Geometric Mean

Standard Deviation

titer

Day 28

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.
OG002	GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)

Secondary

Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (Pan-Ig ELISA)

Geometric mean fold rise (GMFR) of anti-norovirus GI.1 VLP antibody titers as measured by Pan-Ig ELISA.

Posted

Geometric Mean

Standard Deviation

ratio

Day 28

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.
OG002	GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)

Secondary

Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (Pan-Ig ELISA)

Geometric mean fold rise (GMFR) of anti-norovirus GII.4 VLP antibody titers as measured by Pan-Ig ELISA.

Posted

Geometric Mean

Standard Deviation

ratio

Day 28

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.
OG002	GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)

Secondary

Percentage of Participants With a Seroresponse in Both Serum Anti-norovirus GI.1 VLP and GII.4 VLP (HBGA)

Seroresponse is defined as 4-fold rise or greater in serum anti-norovirus antibody titers for both GI.1 virus-Like particle (VLP) and GII.4 VLP as measured by histoblood group antigen (HBGA) binding assay.

Participants from the Per Protocol Set, all participants in Full Analysis Set, who had evaluable blood samples at baseline, and Day 28 within the specified window (+/- 7 days), and did not have major protocol violations, with data available for this outcome measure.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline and Day 28

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.

Secondary

Percentage of Participants With a Seroresponse in Serum GI.1 VLP Antibody Titers (HBGA)

Seroresponse is defined as 4-fold rise or greater in serum anti-norovirus antibody titers for GI.1 virus-Like particle (VLP) as measured by HBGA binding assay.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline and Day 28

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.
OG002	GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)

Secondary

Percentage of Participants With a Seroresponse in Serum GII.4 VLP Antibody Titers (HBGA)

Seroresponse is defined as 4-fold rise or greater in serum anti-norovirus antibody titers for GII.4 virus-Like particle (VLP) as measured by HBGA binding assay.

Posted

Number

95% Confidence Interval

percentage of participants

Baseline and Day 28

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.
OG002

Secondary

Blocking Titers 50 (BT50) of Anti-Norovirus GI.1 VLP Antibody Titers (HBGA)

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

Posted

Geometric Mean

Standard Deviation

titer

Day 28

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.
OG002	GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)

Secondary

Blocking Titers 50 (BT50) of Anti-Norovirus GII.4 VLP Antibody Titers (HBGA)

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

Posted

Geometric Mean

Standard Deviation

titer

Day 28

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.
OG002	GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)

Secondary

Geometric Mean Fold Rise (GMFR) of GI.1 VLP Antibody Titers (HBGA)

Geometric mean fold rise (GMFR) of anti-norovirus GI.1 VLP antibody titers as measured by HBGA binding assay.

Posted

Geometric Mean

Standard Deviation

ratio

Day 28

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.
OG002	GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)

Secondary

Geometric Mean Fold Rise (GMFR) of GII.4 VLP Antibody Titers (HBGA)

Geometric mean fold rise (GMFR) of anti-norovirus GII.4 VLP antibody titers as measured by the HBGA binding assay.

Posted

Geometric Mean

Standard Deviation

ratio

Day 28

ID	Title	Description
OG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.
OG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.
OG002	GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Saline Placebo + GI.1/GII.4 15/15 μg (No MPL)	Intramuscular (IM) saline placebo on Day 1, followed by IM norovirus bivalent virus like particle (VLP) vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no monophosphoryl lipid A [MPL]), on Day 365.	4	153	33	153
EG001	GI.1/GII.4 15/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide, (no MPL) on Day 365.	4	145	24	145
EG002	GI.1/GII.4 50/50 μg - MPL 50 μg + GI.1/GII.4 15/15 μg (no MPL)	IM norovirus bivalent VLP vaccine (50 µg of GI.1 norovirus VLP and 50 µg GII.4 norovirus VLP) adjuvanted with 50 µg MPL and 500 µg aluminum hydroxide, on Day 1, followed by IM norovirus bivalent VLP vaccine (15 µg of GI.1 norovirus VLP and 15 µg GII.4 norovirus VLP) adjuvanted with 500 µg aluminum hydroxide (no MPL), on Day 365.	6	154	25	154

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Cardiac arrest	Cardiac disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected153 at risk EG0011 affected145 at risk EG0020 affected154 at risk
Basedow's disease	Endocrine disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected153 at risk EG0010 affected145 at risk EG0021 affected154 at risk
Retinal detachment	Eye disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected153 at risk EG0010 affected145 at risk EG0020 affected154 at risk
Injection site pain	General disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected153 at risk EG0010 affected145 at risk EG0021 affected154 at risk
Kidney infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected153 at risk EG0011 affected145 at risk EG0020 affected154 at risk
Sepsis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected153 at risk EG0011 affected145 at risk EG0020 affected154 at risk
Urinary tract infection	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0000 affected153 at risk EG0011 affected145 at risk EG0020 affected154 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0000 affected153 at risk EG0010 affected145 at risk EG0021 affected154 at risk
Intentional overdose	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0000 affected153 at risk EG0011 affected145 at risk EG0020 affected154 at risk
Pelvic fracture	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0000 affected153 at risk EG0010 affected145 at risk EG0021 affected154 at risk
Rib fracture	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0001 affected153 at risk EG0010 affected145 at risk EG0020 affected154 at risk
Road traffic accident	Injury, poisoning and procedural complications	MedDRA 17.0	Systematic Assessment	EG0000 affected153 at risk EG0010 affected145 at risk EG0021 affected154 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected153 at risk EG0010 affected145 at risk EG0021 affected154 at risk
Migraine	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected153 at risk EG0011 affected145 at risk EG0020 affected154 at risk
Neuralgic amyotrophy	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected153 at risk EG0010 affected145 at risk EG0021 affected154 at risk
Abortion spontaneous	Pregnancy, puerperium and perinatal conditions	MedDRA 17.0	Systematic Assessment	EG0001 affected153 at risk EG0011 affected145 at risk EG0021 affected154 at risk
Depression	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected153 at risk EG0011 affected145 at risk EG0021 affected154 at risk
Post-traumatic stress disorder	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected153 at risk EG0010 affected145 at risk EG0021 affected154 at risk
Schizophrenia	Psychiatric disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected153 at risk EG0010 affected145 at risk EG0020 affected154 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0007 affected153 at risk EG0013 affected145 at risk EG0025 affected154 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0003 affected153 at risk EG0014 affected145 at risk EG0023 affected154 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 17.0	Systematic Assessment	EG0003 affected153 at risk EG0013 affected145 at risk EG0021 affected154 at risk
Fatigue	General disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected153 at risk EG0011 affected145 at risk EG0024 affected154 at risk
Injection site bruising	General disorders	MedDRA 17.0	Systematic Assessment	EG0004 affected153 at risk EG0011 affected145 at risk EG0020 affected154 at risk
Injection site pain	General disorders	MedDRA 17.0	Systematic Assessment	EG0000 affected153 at risk EG0013 affected145 at risk EG0021 affected154 at risk
Nasopharyngitis	Infections and infestations	MedDRA 17.0	Systematic Assessment	EG0002 affected153 at risk EG0014 affected145 at risk EG0025 affected154 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0004 affected153 at risk EG0012 affected145 at risk EG0022 affected154 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0001 affected153 at risk EG0015 affected145 at risk EG0022 affected154 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 17.0	Systematic Assessment	EG0003 affected153 at risk EG0010 affected145 at risk EG0024 affected154 at risk
Headache	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG00011 affected153 at risk EG0015 affected145 at risk EG00210 affected154 at risk
Dizziness	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected153 at risk EG0013 affected145 at risk EG0021 affected154 at risk
Sinus headache	Nervous system disorders	MedDRA 17.0	Systematic Assessment	EG0002 affected153 at risk EG0010 affected145 at risk EG0024 affected154 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 17.0	Systematic Assessment	EG0004 affected153 at risk EG0011 affected145 at risk EG0022 affected154 at risk

ID	Term
D002712	Chlorides
D006851	Hydrochloric Acid
D017606	Chlorine Compounds
D007287	Inorganic Chemicals
D017670	Sodium Compounds