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Safety and Immunogenicity of Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine in an Elderly Population

Sponsor
Takeda (Industry)
Overall Status
Completed
CT.gov ID
NCT02661490
Collaborator
(none)
320
Enrollment
10
Locations
5
Arms
19.9
Actual Duration (Months)
32
Patients Per Site
1.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to further develop a formulation and dose regimen of the norovirus GI.1/GII.4 bivalent virus-like particle (VLP) vaccine that is immunogenic and safe in an elderly population aged 60 years and above.

Condition or Disease Intervention/Treatment Phase
  • Biological: Norovirus GI.1/GII.4 Bivalent VLP Vaccine
  • Drug: 0.9% sodium chloride (saline)
  • Biological: Norovirus GI.1/GII.4 Bivalent VLP Vaccine
 Phase 2

Detailed Description

The vaccine being tested in this study is called norovirus GI.1/GII.4 bivalent virus-like particle (VLP) vaccine adjuvanted with aluminum hydroxide (Formulation A) or adjuvanted with monophosphoryl lipid A (MPL) and aluminum hydroxide (Formulation B). Two norovirus vaccine formulations are being tested to select for further development the formulation that will generate an optimal specific antibody response that may provide protection against norovirus and is safe in a population aged 60 years and above. This study will look at side effects and the level of antibodies to norovirus formed in people who will be injected with different formulations of the norovirus vaccine candidate.

The study will enroll approximately 325 patients. Participants will be randomly assigned (by chance) to one of five treatment groups.

  • Norovirus GI.1/GII.4 bivalent VLP vaccine (Formulation A) 1-dose, participants ≥ 60 years

  • Norovirus GI.1/GII.4 bivalent VLP vaccine (Formulation A) 2-dose, participants ≥ 60 years

  • Norovirus GI.1/GII.4 bivalent VLP vaccine (Formulation B) 1-dose, participants ≥ 60 years

  • Norovirus GI.1/GII.4 bivalent VLP vaccine (Formulation B) 2-dose, participants ≥ 60 years

  • Norovirus GI.1/GII.4 bivalent VLP vaccine (Formulation A) 1-dose, participants 18 to 49 years All participants in the age of 60 years and older will be administered either NoV vaccine (Formulation A or B) or placebo on Day 1 and NoV vaccine (Formulation A or B) on Day 29 of the study. In order to keep the treatment arms undisclosed to the patient and the doctor, those randomized to the one dose groups will receive a dose of placebo (this is a saline solution that has no active ingredient) on Day 1 followed by the NoV vaccine on Day 29. Those randomized to 2 doses with receive the NoV vaccine on Day 1 and Day 29. In case of an urgent medical need a participant can be unblinded.

Adults aged 18 to 49 will receive placebo on Day 1 followed by NoV vaccine Formulation A on Day 29.

Participants will be asked to record any reactions/ symptoms that may be related or not to the vaccine in a diary card for 28 days after each vaccination.

This multi-center trial will be conducted in the United States of America. The overall time to participate in this study is up to 393 days. Participants will make multiple visits to the clinic including a final follow-up visit on Day 393.

Study Design

Study Type:
Interventional
Actual Enrollment :
320 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, Safety and Immunogenicity Trial of Norovirus GI.1/GII.4 Bivalent Virus-Like Particle Vaccine in Healthy Elderly Adults
Actual Study Start Date :
Feb 1, 2016
Actual Primary Completion Date :
Oct 28, 2016
Actual Study Completion Date :
Sep 29, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm 1: NoV Vaccine Formulation A _1-Dose

Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29.

Biological: Norovirus GI.1/GII.4 Bivalent VLP Vaccine
Norovirus GI.1/GII.4 bivalent VLP vaccine adjuvanted with aluminum hydroxide, without MPL for IM injection

Drug: 0.9% sodium chloride (saline)
norovirus bivalent placebo-matching vaccine
Experimental: Arm 2: NoV Vaccine Formulation A _2-Dose

Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29.

Biological: Norovirus GI.1/GII.4 Bivalent VLP Vaccine
Norovirus GI.1/GII.4 bivalent VLP vaccine adjuvanted with aluminum hydroxide, without MPL for IM injection
Experimental: Arm 3: NoV Vaccine Formulation B_1-Dose

Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29.

Drug: 0.9% sodium chloride (saline)
norovirus bivalent placebo-matching vaccine

Biological: Norovirus GI.1/GII.4 Bivalent VLP Vaccine
Norovirus GI.1/GII.4 bivalent VLP vaccine adjuvanted with MPL and aluminum hydroxide for IM injection
Experimental: Arm 4: NoV Vaccine Formulation B_2-Dose

Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29.

Biological: Norovirus GI.1/GII.4 Bivalent VLP Vaccine
Norovirus GI.1/GII.4 bivalent VLP vaccine adjuvanted with MPL and aluminum hydroxide for IM injection
Experimental: Arm 5: NoV Vaccine Formulation A_1-Dose

Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.

Biological: Norovirus GI.1/GII.4 Bivalent VLP Vaccine
Norovirus GI.1/GII.4 bivalent VLP vaccine adjuvanted with aluminum hydroxide, without MPL for IM injection

Drug: 0.9% sodium chloride (saline)
norovirus bivalent placebo-matching vaccine

Outcome Measures

Primary Outcome Measures

  1. Percentage of Participants With a 4-Fold Rise or Greater in Serum Anti-norovirus Antibody Titers for Both GI.1 and GII.4 Virus Like Particles (VLP) as Measured by Histoblood Group Antigen (HBGA) Blocking Assay on Day 57 [Day 57]

  2. Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site for 7-day Period (Including Day of Vaccination) After First Vaccination on Day 1 [Within 7 days of first vaccination on Day 1]

    Solicited local AEs at the injection site that occurred within 7 days after each vaccination were collected using a diary and included pain, erythema swelling and induration.

  3. Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site for 7-day Period (Including Day of Vaccination) After Second Vaccination on Day 29 [Within 7 days of second vaccination on Day 29]

    Solicited local AEs at the injection site that occurred within 7 days after each vaccination were collected using a diary and included pain, erythema, swelling and induration.

  4. Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 7-day Period (Including Day of Vaccination) After First Vaccination on Day 1 [Within 7 days of first vaccination on Day 1]

    Solicited systemic AEs that occurred within 7 days after each vaccination were collected using a diary and included headache, fatigue, myalgia, arthralgia, vomiting, and diarrhea.

  5. Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 7-day Period (Including Day of Vaccination) After Second Vaccination on Day 29 [Within 7 days of second vaccination on Day 29]

    Solicited systemic AEs that occurred within 7 days after each vaccination were collected using a diary and included headache, fatigue, myalgia, arthralgia, vomiting, and diarrhea.

  6. Percentage of Participants With Elevated Body Temperature ≥38°C (Defined as Fever) for 7-day Period (Including Day of Vaccination) After First Vaccination on Day 1 [Within 7 days of first vaccination on Day 1]

    The body temperature measurement was performed using the thermometer for 7 days after each vaccination. The highest body temperature observed each day was recorded on the diary card. An elevated temperature is ≥ 38 °C or 100.4°F (considered as fever).

  7. Percentage of Participants With Elevated Body Temperature ≥38°C (Defined as Fever) for 7-day Period (Including Day of Vaccination) After Second Vaccination on Day 29 [Within 7 days of second vaccination on Day 29]

    The body temperature measurement was performed using the thermometer for 7 days after each vaccination. The highest body temperature observed each day was recorded on the diary card. An elevated temperature is ≥ 38 °C or 100.4°F (considered as fever).

  8. Percentage of Participants With At Least One Unsolicited Adverse Event (AE) Within 28-days After First Vaccination on Day 1 [Within 28 days of first vaccination on Day 1]

    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.

  9. Percentage of Participants With At Least One Unsolicited Adverse Event (AE) Within 28-days After Second Vaccination on Day 29 [Within 28 days of second vaccination on Day 29]

    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.

  10. Percentage of Participants With At Least One Serious Adverse Event (SAE) [From first vaccination up to Day 393]

    An SAE is any untoward medical occurrence 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 4-Fold Rise or Greater in Serum Anti-norovirus Antibody Titers for Both GI.1 VLP and GII.4 VLP as Measured by HBGA Blocking Assay [Days 8, 29, 36, 211 and 393]

  2. Percentage of Participants With a 4-Fold Rise or Greater in Serum Anti-norovirus GI.1 VLP Antibody Titers (HBGA) [Days 8, 29, 36, 57, 211 and 393]

  3. Percentage of Participants With a 4-Fold Rise or Greater in Serum Anti-norovirus GII.4 VLP Antibody Titers (HBGA) [Days 8, 29, 36, 57, 211 and 393]

  4. Geometric Mean Titer (GMT) GI.1 VLP Antibody Titers (HBGA) [Baseline (Day 1), Days 8, 29, 36, 57, 211 and 393]

    GMT GI.1 VLP antibody titers measured by HBGA blocking assay are reported.

  5. GMT of Anti-norovirus GII.4 VLP Antibody Titers (HBGA) [Baseline (Day 1), Days 8, 29, 36, 57, 211 and 393]

    GMT of anti-norovirus GII.4 VLP antibody titers measured by HBGA blocking assay are reported.

  6. Geometric Mean Fold Rise (GMFR) of Anti-norovirus GI.1 VLP Antibody Titers (HBGA) [Days 8, 29, 36, 57, 211 and 393]

    GMFR of anti-norovirus GI.1 VLP antibody titers measured by HBGA blocking assay are reported. The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level.

  7. GMFR of Anti-norovirus GII.4 VLP Antibody Titers (HBGA) [Days 8, 29, 36, 57, 211 and 393]

    GMFR of anti-norovirus GII.4 VLP antibody titers measured by HBGA blocking assay are reported. The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level.

  8. 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 Total Immunoglobulin-Enzyme-linked Immunosorbent Assay (Pan-Ig ELISA) [Days 8, 29, 36, 57, 211 and 393]

    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 measured by Pan-Ig ELISA are reported.

  9. Percentage of Participants With a 4-Fold Rise or Greater in Serum Anti-norovirus GI.1 VLP Antibody Titers (Pan-Ig ELISA) [Days 8, 29, 36, 57, 211 and 393]

    Percentage of participants with a 4-Fold rise or greater in serum anti-norovirus GI.1 VLP antibody titers measured by Pan-Ig ELISA are reported.

  10. Percentage of Participants With a 4-Fold Rise or Greater in Serum Anti-norovirus GII.4 VLP Antibody Titers (Pan-Ig ELISA) [Days 8, 29, 36, 57, 211 and 393]

    Percentage of participants with a 4-fold rise or greater in serum anti-norovirus GII.4 VLP antibody titers measured by Pan-Ig ELISA are reported.

  11. GMT of Anti-norovirus GI.1 VLP Antibody Titers (Pan-Ig ELISA) [Baseline (Day 1), Days 8, 29, 36, 57, 211 and 393]

    GMT of anti-norovirus GI.1 VLP antibody titers measured by Pan-Ig ELISA are reported.

  12. GMT of Anti-norovirus GII.4 VLP Antibody Titers (Pan-Ig ELISA) [Baseline (Day 1), Days 8, 29, 36, 57, 211 and 393]

    GMT of anti-norovirus GII.4 VLP antibody titers measured by Pan-Ig ELISA are reported.

  13. GMFR of Anti-norovirus GI.1 VLP Antibody Titers (Pan-Ig ELISA) [Days 8, 29, 36, 57, 211 and 393]

    GMFR of anti-norovirus GI.1 VLP antibody titers measured by Pan-Ig ELISA are reported. The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level.

  14. GMFR of Anti-norovirus GII.4 VLP Antibody Titers (Pan-Ig ELISA) [Days 8, 29, 36, 57, 211 and 393]

    GMFR of anti-norovirus GII.4 VLP antibody titers measured by Pan-Ig ELISA are reported. The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level.

  15. Percentage of Participants With At Least One Adverse Event of Special Interest (AESI) [From first vaccination up to Day 393]

    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.

  16. Percentage of Participants With At Least One Adverse Event (AE) Leading to Participant's Withdrawal From the Study [From first vaccination up to Day 393]

    Withdrawal due to an AE will occur if the participant experiences an AE that requires early termination of treatment, 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:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:

  1. Is aged 18 to 49 years, or 60 years and older at the time of enrollment;

  2. Participants who are in good health, or in stable health status with no exclusionary medical or neuropsychiatric conditions 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. Participant 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;

  4. Participants who can comply with trial procedures and are available for the duration of follow-up.

Exclusion Criteria:

  1. Has a known hypersensitivity or allergy to any of the Norovirus (NoV) GI.1/GII.4 Bivalent virus-like particle (VLP) Vaccine components;

  2. Has a clinically significant active infection (as assessed by the Investigator) or body temperature ≥38°C/100.4°F within 3 days of the intended date of vaccination;

  3. Participants with the presence of significant acute or chronic, uncontrolled medical or neuropsychiatric illness. Uncontrolled was defined as:

Requiring institution of new medical or surgical treatment within 3 months prior to immunization, or Requiring a change in medication dosage in the 3 months prior to immunization due to uncontrolled symptoms or drug toxicity (elective dosage adjustments in stable participants were acceptable), or Hospitalization or an event fulfilling the definition of a serious adverse event within 3 months prior immunization.

  1. Has any unstable medical or neuropsychiatric condition, which in the Investigator's opinion poses a risk of unusual magnitude for the participant's age group of hospitalization, death, or an event meeting the definition of a serious adverse event within 2 months of immunization. The intent of this criterion is to recognize and allow for the frequent existence of significant health concerns in this population; but exclude those participants who are experiencing an acute decline in health status;

  2. Has any medical or neuropsychiatric condition, which in the Investigator's opinion, rendered the participant incompetent to provide informed consent or unable to provide valid safety observations and reports;

  3. 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;

  4. Participants with any history of progressive or severe neurologic disorder, history of seizure, or history of neuro-inflammatory disease (e.g. Guillain-Barre syndrome);

  5. Participants with 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;

  6. Has known or suspected autoimmune disease;

  7. Has known or suspected impairment/alteration of immune function, including:

Chronic use of oral steroids (Equivalent to 20 mg/day prednisone ≥ 12 weeks/≥ 2 mg/kg body weight/day prednisone ≥ 2 weeks) within 60 days prior to Day 1 (use of inhaled, intranasal, or topical corticosteroids is allowed).

Receipt of parenteral steroids (Equivalent to 20 mg/day prednisone ≥ 12 weeks/≥ 2 mg/kg body weight/day prednisone ≥ 2 weeks) within 60 days prior to Day 1.

Receipt of immunosuppressive therapy within 3 months prior to Day 1. Receipt of immunostimulants within 60 days prior to Day 1. Receipt of parenteral, epidural or intra-articular immunoglobulin preparation, blood products, and/or plasma derivatives within 3 months prior to Day 1 or planned during the full length of the trial.

Human Immunodeficiency Virus (HIV) infection or HIV-related disease. Genetic immunodeficiency.

  1. Has abnormalities of splenic or thymic function;

  2. Has any significant disorder of coagulation or treatment with anticoagulant therapy that would increase the risk of intramuscular (IM) injection. Persons receiving prophylactic antiplatelet medication such as low dose of acetylsalicylic acid are eligible;

  3. Has any serious chronic or progressive disease according to judgment of the Investigator: cancer (malignancy other than resolved/excised skin lesion), insulin dependent Type I diabetes (Type II diabetes is accepted), cardiac, renal or hepatic disease;

  4. Has body mass index (BMI) greater than or equal to 35 kg/m2 (= weight in kg/[height in meters2]);

  5. 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;

  6. Participants who received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this trial or who are planning to receive any vaccine within 28 days of investigational vaccine administration;

  7. Participants involved in trial conduct or their first degree relatives;

  8. Has history of substance or alcohol abuse within the past 2 years;

  9. Females who are pregnant or breastfeeding;

  10. If female of childbearing potential, sexually active with a male partner who has not been sterilized, and has not used any of the "acceptable contraceptive methods" for at least 2 months prior to trial entry:

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.

Acceptable birth control methods are defined as one 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 six months prior to the participants' trial entry.

  1. If female of childbearing potential and sexually active, refusal to use an "acceptable contraceptive method" from Day 1 and throughout the duration of the trial. In addition, they must be advised not to donate ova during this period;

  2. Females with any positive or indeterminate pregnancy test.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Simon Williamson Clinic Birmingham Alabama United States 35211
2 Fountain Hills Family Practice, P.C. Fountain Hills Arizona United States 85268
3 Southwest Family Medicine Littleton Colorado United States 80127
4 Miami Research Associates Miami Florida United States 33143
5 Johnson County Clin-Trials Lenexa Kansas United States 66219
6 St. Louis University, School of Medicine Saint Louis Missouri United States 63104
7 Regional Clinical Research Inc. Endwell New York United States 13760
8 University of Rochester Rochester New York United States 14642
9 Cincinnati Childrens Hospital Medical Center Cincinnati Ohio United States 45229-3039
10 Group Health Research Institute Seattle Washington United States 98101

Sponsors and Collaborators

  • Takeda

Investigators

  • Study Director: Medical Director Clinical Science, Takeda

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Takeda
ClinicalTrials.gov Identifier:
NCT02661490
Other Study ID Numbers:
  • NOR-204
  • U1111-1162-4913
First Posted:
Jan 22, 2016
Last Update Posted:
May 18, 2020
Last Verified:
Apr 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by Takeda
Norovirus
Additional relevant MeSH terms:
Vaccines

Study Results

Participant Flow

Recruitment Details Participants took part in the study at 10 investigative sites in United States from 1 February 2016 to 31 October 2017.
Pre-assignment Detail Healthy elderly volunteers were enrolled and randomized in 1:1:1:1 ratio in 4 arm groups to receive either one or two doses of one of the 2 formulations (A or B) of norovirus (NoV) GI.1/GII4 bivalent virus like particle (VLP) vaccine or placebo. Healthy young adults received both placebo and formulation A.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Period Title: Overall Study
STARTED 76 74 72 72 26
COMPLETED 73 72 70 71 23
NOT COMPLETED 3 2 2 1 3

Baseline Characteristics

Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose Total
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29. Total of all reporting groups
Overall Participants 76 74 72 72 26 320
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
78.0
(9.14)
77.4
(9.32)
76.7
(9.22)
77.7
(9.07)
77.4
(9.15)
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
34.6
(8.46)
34.6
(8.46)
Sex: Female, Male (Count of Participants)
Female
44
57.9%
41
55.4%
40
55.6%
40
55.6%
16
61.5%
181
56.6%
Male
32
42.1%
33
44.6%
32
44.4%
32
44.4%
10
38.5%
139
43.4%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino
4
5.3%
6
8.1%
3
4.2%
4
5.6%
2
7.7%
19
5.9%
Not Hispanic or Latino
72
94.7%
68
91.9%
69
95.8%
68
94.4%
24
92.3%
301
94.1%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Asian
2
2.6%
0
0%
1
1.4%
2
2.8%
2
7.7%
7
2.2%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
1
1.4%
0
0%
1
3.8%
2
0.6%
Black or African American
2
2.6%
5
6.8%
2
2.8%
0
0%
2
7.7%
11
3.4%
White
72
94.7%
69
93.2%
68
94.4%
70
97.2%
20
76.9%
299
93.4%
More than one race
0
0%
0
0%
0
0%
0
0%
1
3.8%
1
0.3%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
Region of Enrollment (Count of Participants)
United States
76
100%
74
100%
72
100%
72
100%
26
100%
320
100%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]
166.8
(9.95)
167.3
(9.52)
168.0
(9.17)
167.4
(10.26)
167.3
(9.69)
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]
169.4
(11.42)
169.4
(11.42)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]
75.56
(14.376)
73.76
(13.804)
77.26
(14.404)
74.34
(13.965)
75.22
(14.131)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]
78.22
(15.357)
78.22
(15.357)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]
27.01
(3.554)
26.28
(3.958)
27.29
(3.899)
26.46
(3.909)
26.76
(3.833)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]
27.22
(4.481)
27.22
(4.481)

Outcome Measures

1. Primary Outcome
Title Percentage of Participants With a 4-Fold Rise or Greater in Serum Anti-norovirus Antibody Titers for Both GI.1 and GII.4 Virus Like Particles (VLP) as Measured by Histoblood Group Antigen (HBGA) Blocking Assay on Day 57
Description
Time Frame Day 57

Outcome Measure Data

Analysis Population Description
Per Protocol Set (PPS) included all participants in the Full Analysis Set (FAS), who receive the planned vaccination [both doses of vaccine, i.e. Norovirus (NoV) VLP vaccine or placebo], and did not have major protocol violations. Overall number of participants analyzed is the number of participants with data available for analyses.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 71 65 62 66 24
Number (95% Confidence Interval) [percentage of participants]
42.3
55.7%
41.5
56.1%
56.5
78.5%
63.6
88.3%
45.8
176.2%
2. Primary Outcome
Title Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site for 7-day Period (Including Day of Vaccination) After First Vaccination on Day 1
Description Solicited local AEs at the injection site that occurred within 7 days after each vaccination were collected using a diary and included pain, erythema swelling and induration.
Time Frame Within 7 days of first vaccination on Day 1

Outcome Measure Data

Analysis Population Description
Safety Analysis Set (SAF) included all participants who received at least 1 dose of vaccine (NoV VLP vaccine or placebo). Number analyzed is the number of participants with evaluable data for the specific category.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 76 74 72 72 25
Any Solicited Local AEs
6.6
8.7%
26.0
35.1%
15.3
21.3%
34.7
48.2%
4.0
15.4%
Pain
5.3
7%
23.3
31.5%
9.7
13.5%
34.7
48.2%
4.0
15.4%
Erythema
1.3
1.7%
2.7
3.6%
4.2
5.8%
1.4
1.9%
4.0
15.4%
Swelling
0.0
0%
2.7
3.6%
2.8
3.9%
1.4
1.9%
0.0
0%
Induration
0.0
0%
1.4
1.9%
1.4
1.9%
1.4
1.9%
0.0
0%
3. Primary Outcome
Title Percentage of Participants With Solicited Local Adverse Events (AEs) at Injection Site for 7-day Period (Including Day of Vaccination) After Second Vaccination on Day 29
Description Solicited local AEs at the injection site that occurred within 7 days after each vaccination were collected using a diary and included pain, erythema, swelling and induration.
Time Frame Within 7 days of second vaccination on Day 29

Outcome Measure Data

Analysis Population Description
SAF included all participants who received at least 1 dose of vaccine (NoV VLP vaccine or placebo). Overall number of participants analyzed is the number of participants with data available for analyses.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 73 69 68 66 24
Any Solicited Local AEs
37.0
48.7%
21.7
29.3%
38.2
53.1%
39.4
54.7%
41.7
160.4%
Pain
32.9
43.3%
21.7
29.3%
38.2
53.1%
37.9
52.6%
41.7
160.4%
Erythema
2.7
3.6%
0.0
0%
1.5
2.1%
3.0
4.2%
0.0
0%
Swelling
1.4
1.8%
0.0
0%
1.5
2.1%
1.5
2.1%
0.0
0%
Induration
1.4
1.8%
0.0
0%
1.5
2.1%
1.5
2.1%
0.0
0%
4. Primary Outcome
Title Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 7-day Period (Including Day of Vaccination) After First Vaccination on Day 1
Description Solicited systemic AEs that occurred within 7 days after each vaccination were collected using a diary and included headache, fatigue, myalgia, arthralgia, vomiting, and diarrhea.
Time Frame Within 7 days of first vaccination on Day 1

Outcome Measure Data

Analysis Population Description
SAF included all participants who received at least 1 dose of vaccine (NoV VLP vaccine or placebo). Number analyzed is the number of participants with evaluable data for the specific category.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 76 74 72 72 25
Any solicited systemic AEs
28.9
38%
34.2
46.2%
30.6
42.5%
44.4
61.7%
36.0
138.5%
Headache
7.9
10.4%
2.7
3.6%
11.1
15.4%
12.5
17.4%
20.0
76.9%
Fatigue
18.4
24.2%
24.7
33.4%
9.7
13.5%
27.8
38.6%
28.0
107.7%
Myalgia
5.3
7%
13.7
18.5%
11.1
15.4%
20.8
28.9%
16.0
61.5%
Arthralgia
5.3
7%
8.2
11.1%
6.9
9.6%
6.9
9.6%
4.0
15.4%
Vomiting
0.0
0%
1.4
1.9%
0.0
0%
2.8
3.9%
0.0
0%
Diarrhea
5.3
7%
6.8
9.2%
8.3
11.5%
18.1
25.1%
8.0
30.8%
5. Primary Outcome
Title Percentage of Participants With Solicited Systemic Adverse Events (AEs) for 7-day Period (Including Day of Vaccination) After Second Vaccination on Day 29
Description Solicited systemic AEs that occurred within 7 days after each vaccination were collected using a diary and included headache, fatigue, myalgia, arthralgia, vomiting, and diarrhea.
Time Frame Within 7 days of second vaccination on Day 29

Outcome Measure Data

Analysis Population Description
SAF included all participants who received at least 1 dose of vaccine (NoV VLP vaccine or placebo). Overall number of participants analyzed is the number of participants with data available for analyses.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 73 69 68 66 24
Any solicited systemic AEs
19.2
25.3%
20.3
27.4%
20.6
28.6%
28.8
40%
16.7
64.2%
Headache
8.2
10.8%
5.8
7.8%
5.9
8.2%
6.1
8.5%
4.2
16.2%
Fatigue
12.3
16.2%
15.9
21.5%
13.2
18.3%
15.2
21.1%
8.3
31.9%
Myalgia
6.8
8.9%
5.8
7.8%
7.4
10.3%
13.6
18.9%
4.2
16.2%
Arthralgia
4.1
5.4%
7.2
9.7%
4.4
6.1%
6.1
8.5%
4.2
16.2%
Vomiting
0.0
0%
0.0
0%
0.0
0%
1.5
2.1%
0.0
0%
Diarrhea
1.4
1.8%
4.3
5.8%
2.9
4%
4.5
6.3%
0.0
0%
6. Primary Outcome
Title Percentage of Participants With Elevated Body Temperature ≥38°C (Defined as Fever) for 7-day Period (Including Day of Vaccination) After First Vaccination on Day 1
Description The body temperature measurement was performed using the thermometer for 7 days after each vaccination. The highest body temperature observed each day was recorded on the diary card. An elevated temperature is ≥ 38 °C or 100.4°F (considered as fever).
Time Frame Within 7 days of first vaccination on Day 1

Outcome Measure Data

Analysis Population Description
SAF included all participants who received at least 1 dose of vaccine (NoV VLP vaccine or placebo). Overall number of participants analyzed is the number of participants with data available for analyses.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 76 72 72 71 25
Number [percentage of participants]
0.0
0%
0.0
0%
0.0
0%
0.0
0%
0.0
0%
7. Primary Outcome
Title Percentage of Participants With Elevated Body Temperature ≥38°C (Defined as Fever) for 7-day Period (Including Day of Vaccination) After Second Vaccination on Day 29
Description The body temperature measurement was performed using the thermometer for 7 days after each vaccination. The highest body temperature observed each day was recorded on the diary card. An elevated temperature is ≥ 38 °C or 100.4°F (considered as fever).
Time Frame Within 7 days of second vaccination on Day 29

Outcome Measure Data

Analysis Population Description
SAF included all participants who received at least 1 dose of vaccine (NoV VLP vaccine or placebo). Overall number of participants analyzed is the number of participants with data available for analyses.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 73 69 68 66 24
Number [percentage of participants]
0.0
0%
0.0
0%
0.0
0%
1.5
2.1%
0.0
0%
8. Primary Outcome
Title Percentage of Participants With At Least One Unsolicited Adverse Event (AE) Within 28-days After First Vaccination on Day 1
Description An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.
Time Frame Within 28 days of first vaccination on Day 1

Outcome Measure Data

Analysis Population Description
SAF included all participants who received at least 1 dose of vaccine (NoV VLP vaccine or placebo).
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 76 74 72 72 25
Number [percentage of participants]
32.9
43.3%
28.4
38.4%
33.3
46.3%
26.4
36.7%
20.0
76.9%
9. Primary Outcome
Title Percentage of Participants With At Least One Unsolicited Adverse Event (AE) Within 28-days After Second Vaccination on Day 29
Description An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment.
Time Frame Within 28 days of second vaccination on Day 29

Outcome Measure Data

Analysis Population Description
SAF included all participants who received at least 1 dose of vaccine (NoV VLP vaccine or placebo). Overall number of participants analyzed is number of participants with data available for analyses.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 73 69 68 66 24
Number [percentage of participants]
34.2
45%
18.8
25.4%
25.0
34.7%
30.3
42.1%
8.3
31.9%
10. Primary Outcome
Title Percentage of Participants With At Least One Serious Adverse Event (SAE)
Description An SAE is any untoward medical occurrence 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 From first vaccination up to Day 393

Outcome Measure Data

Analysis Population Description
SAF included all participants who received at least 1 dose of vaccine (NoV VLP vaccine or placebo).
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 76 74 72 72 25
Number [percentage of participants]
9.2
12.1%
12.2
16.5%
23.6
32.8%
12.5
17.4%
0.0
0%
11. Secondary Outcome
Title 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 HBGA Blocking Assay
Description
Time Frame Days 8, 29, 36, 211 and 393

Outcome Measure Data

Analysis Population Description
PPS included all participants in the FAS, who received the planned vaccination (both doses of vaccine, i.e. NoV VLP vaccine or placebo), and did not have major protocol violations. Number analyzed is the number of participants with evaluable data at the given time point.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 72 67 66 66 24
Day 8
0.0
0%
33.8
45.7%
0.0
0%
55.4
76.9%
0.0
0%
Day 29
0.0
0%
40.9
55.3%
0.0
0%
54.5
75.7%
0.0
0%
Day 36
26.4
34.7%
45.5
61.5%
34.4
47.8%
63.6
88.3%
43.5
167.3%
Day 211
15.5
20.4%
18.2
24.6%
28.1
39%
30.3
42.1%
8.7
33.5%
Day 393
12.9
17%
10.9
14.7%
19.0
26.4%
16.9
23.5%
13.0
50%
12. Secondary Outcome
Title Percentage of Participants With a 4-Fold Rise or Greater in Serum Anti-norovirus GI.1 VLP Antibody Titers (HBGA)
Description
Time Frame Days 8, 29, 36, 57, 211 and 393

Outcome Measure Data

Analysis Population Description
PPS included all participants in the FAS, who received the planned vaccination (both doses of vaccine, i.e. NoV VLP vaccine or placebo), and did not have major protocol violations. Number analyzed is the number of participants with evaluable data at the given time point.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 72 67 66 66 24
Day 8
1.4
1.8%
63.1
85.3%
0.0
0%
76.9
106.8%
0.0
0%
Day 29
0.0
0%
72.7
98.2%
0.0
0%
77.3
107.4%
0.0
0%
Day 36
55.6
73.2%
74.2
100.3%
65.6
91.1%
89.4
124.2%
60.9
234.2%
Day 57
64.8
85.3%
80.0
108.1%
74.2
103.1%
89.4
124.2%
62.5
240.4%
Day 211
33.8
44.5%
57.6
77.8%
54.7
76%
57.6
80%
26.1
100.4%
Day 393
25.7
33.8%
50.0
67.6%
41.3
57.4%
47.7
66.3%
30.4
116.9%
13. Secondary Outcome
Title Percentage of Participants With a 4-Fold Rise or Greater in Serum Anti-norovirus GII.4 VLP Antibody Titers (HBGA)
Description
Time Frame Days 8, 29, 36, 57, 211 and 393

Outcome Measure Data

Analysis Population Description
PPS included all participants in the FAS, who received the planned vaccination (both doses of vaccine, i.e. NoV VLP vaccine or placebo), and did not have major protocol violations. Number analyzed is the number of participants with evaluable data at the given time point.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 72 67 66 66 24
Day 8
0.0
0%
54.5
73.6%
1.5
2.1%
69.2
96.1%
0.0
0%
Day 29
1.4
1.8%
59.7
80.7%
0.0
0%
71.2
98.9%
0.0
0%
Day 36
56.9
74.9%
62.7
84.7%
53.1
73.8%
71.2
98.9%
78.3
301.2%
Day 57
67.6
88.9%
57.6
77.8%
74.2
103.1%
71.2
98.9%
66.7
256.5%
Day 211
39.4
51.8%
34.8
47%
45.3
62.9%
45.5
63.2%
47.8
183.8%
Day 393
34.3
45.1%
30.8
41.6%
33.3
46.3%
36.9
51.3%
39.1
150.4%
14. Secondary Outcome
Title Geometric Mean Titer (GMT) GI.1 VLP Antibody Titers (HBGA)
Description GMT GI.1 VLP antibody titers measured by HBGA blocking assay are reported.
Time Frame Baseline (Day 1), Days 8, 29, 36, 57, 211 and 393

Outcome Measure Data

Analysis Population Description
PPS included all participants in the FAS, who received the planned vaccination (both doses of vaccine, i.e. NoV VLP vaccine or placebo), and did not have major protocol violations. Number analyzed is the number of participants with evaluable data at the given time point.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 72 67 66 66 24
Baseline (Day 1)
26.5
29.0
26.7
23.9
22.0
Day 8
26.6
282.4
26.5
332.3
21.7
Day 29
26.2
373.6
27.3
285.5
21.7
Day 36
194.2
361.1
280.1
338.9
150.8
Day 57
177.0
353.6
262.2
317.1
117.7
Day 211
81.8
160.5
128.3
126.7
54.1
Day 393
60.2
112.2
85.7
84.6
41.0
15. Secondary Outcome
Title GMT of Anti-norovirus GII.4 VLP Antibody Titers (HBGA)
Description GMT of anti-norovirus GII.4 VLP antibody titers measured by HBGA blocking assay are reported.
Time Frame Baseline (Day 1), Days 8, 29, 36, 57, 211 and 393

Outcome Measure Data

Analysis Population Description
PPS included all participants in the FAS, who received the planned vaccination (both doses of vaccine, i.e. NoV VLP vaccine or placebo), and did not have major protocol violations. Number analyzed is the number of participants with evaluable data at the given time point.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 72 67 66 66 24
Baseline (Day 1)
66.5
100.3
99.5
86.1
78.7
Day 8
60.7
694.9
94.1
994.9
75.2
Day 29
58.6
787.7
82.8
876.1
67.2
Day 36
556.5
757.1
733.8
799.4
1234.5
Day 57
528.0
600.6
790.8
613.6
742.0
Day 211
222.0
298.9
318.6
315.9
280.3
Day 393
188.9
249.8
265.9
278.9
223.4
16. Secondary Outcome
Title Geometric Mean Fold Rise (GMFR) of Anti-norovirus GI.1 VLP Antibody Titers (HBGA)
Description GMFR of anti-norovirus GI.1 VLP antibody titers measured by HBGA blocking assay are reported. The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level.
Time Frame Days 8, 29, 36, 57, 211 and 393

Outcome Measure Data

Analysis Population Description
PPS included all participants in the FAS, who received the planned vaccination (both doses of vaccine, i.e. NoV VLP vaccine or placebo), and did not have major protocol violations. Number analyzed is the number of participants with evaluable data at the given time point.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 72 67 66 66 24
Day 8
1.0
10.1
1.0
14.1
1.0
Day 29
1.0
13.0
1.0
12.0
1.0
Day 36
7.3
12.6
10.6
14.2
7.5
Day 57
6.6
12.1
10.0
13.3
5.3
Day 211
3.2
5.5
4.8
5.3
2.4
Day 393
2.4
3.9
3.2
3.5
1.8
17. Secondary Outcome
Title GMFR of Anti-norovirus GII.4 VLP Antibody Titers (HBGA)
Description GMFR of anti-norovirus GII.4 VLP antibody titers measured by HBGA blocking assay are reported. The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level.
Time Frame Days 8, 29, 36, 57, 211 and 393

Outcome Measure Data

Analysis Population Description
PPS included all participants in the FAS, who received the planned vaccination (both doses of vaccine, i.e. NoV VLP vaccine or placebo), and did not have major protocol violations. Number analyzed is the number of participants with evaluable data at the given time point.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 72 67 66 66 24
Day 8
0.9
6.9
0.9
11.6
0.9
Day 29
0.9
7.9
0.8
10.2
0.9
Day 36
8.4
7.5
7.3
9.3
15.1
Day 57
8.1
5.8
8.4
7.1
9.4
Day 211
3.4
3.0
3.4
3.7
3.8
Day 393
3.0
2.6
2.7
3.2
3.0
18. Secondary Outcome
Title 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 Total Immunoglobulin-Enzyme-linked Immunosorbent Assay (Pan-Ig ELISA)
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 measured by Pan-Ig ELISA are reported.
Time Frame Days 8, 29, 36, 57, 211 and 393

Outcome Measure Data

Analysis Population Description
PPS included all participants in the FAS, who received the planned vaccination (both doses of vaccine, i.e. NoV VLP vaccine or placebo), and did not have major protocol violations. Number analyzed is the number of participants with evaluable data at the given time point.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 72 67 66 66 24
Day 8
0.0
0%
31.8
43%
0.0
0%
52.3
72.6%
0.0
0%
Day 29
1.4
1.8%
47.8
64.6%
0.0
0%
62.1
86.3%
0.0
0%
Day 36
37.5
49.3%
49.3
66.6%
39.1
54.3%
63.6
88.3%
69.6
267.7%
Day 57
52.1
68.6%
43.9
59.3%
58.1
80.7%
62.1
86.3%
62.5
240.4%
Day 211
40.8
53.7%
37.9
51.2%
40.6
56.4%
42.4
58.9%
47.8
183.8%
Day 393
24.3
32%
15.4
20.8%
25.4
35.3%
23.1
32.1%
30.4
116.9%
19. Secondary Outcome
Title Percentage of Participants With a 4-Fold Rise or Greater in Serum Anti-norovirus GI.1 VLP Antibody Titers (Pan-Ig ELISA)
Description Percentage of participants with a 4-Fold rise or greater in serum anti-norovirus GI.1 VLP antibody titers measured by Pan-Ig ELISA are reported.
Time Frame Days 8, 29, 36, 57, 211 and 393

Outcome Measure Data

Analysis Population Description
PPS included all participants in the FAS, who received the planned vaccination (both doses of vaccine, i.e. NoV VLP vaccine or placebo), and did not have major protocol violations. Number analyzed is the number of participants with evaluable data at the given time point.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 72 67 66 66 24
Day 8
0.0
0%
56.1
75.8%
0.0
0%
69.2
96.1%
0.0
0%
Day 29
1.4
1.8%
67.2
90.8%
0.0
0%
80.3
111.5%
8.3
31.9%
Day 36
59.7
78.6%
67.2
90.8%
68.8
95.6%
83.3
115.7%
91.3
351.2%
Day 57
73.2
96.3%
65.2
88.1%
83.9
116.5%
84.8
117.8%
87.5
336.5%
Day 211
62.0
81.6%
63.6
85.9%
70.3
97.6%
72.7
101%
73.9
284.2%
Day 393
48.6
63.9%
41.5
56.1%
52.4
72.8%
60.0
83.3%
60.9
234.2%
20. Secondary Outcome
Title Percentage of Participants With a 4-Fold Rise or Greater in Serum Anti-norovirus GII.4 VLP Antibody Titers (Pan-Ig ELISA)
Description Percentage of participants with a 4-fold rise or greater in serum anti-norovirus GII.4 VLP antibody titers measured by Pan-Ig ELISA are reported.
Time Frame Days 8, 29, 36, 57, 211 and 393

Outcome Measure Data

Analysis Population Description
PPS included all participants in the FAS, who received the planned vaccination (both doses of vaccine, i.e. NoV VLP vaccine or placebo), and did not have major protocol violations. Number analyzed is the number of participants with evaluable data at the given time point.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 72 67 66 66 24
Day 8
0.0
0%
50.0
67.6%
0.0
0%
62.5
86.8%
0.0
0%
Day 29
0.0
0%
70.8
95.7%
0.0
0%
70.8
98.3%
0.0
0%
Day 36
52.8
69.5%
68.7
92.8%
48.4
67.2%
71.2
98.9%
73.9
284.2%
Day 57
70.4
92.6%
63.6
85.9%
67.7
94%
68.2
94.7%
66.7
256.5%
Day 211
60.6
79.7%
53.0
71.6%
50.0
69.4%
53.0
73.6%
52.2
200.8%
Day 393
34.3
45.1%
32.3
43.6%
34.9
48.5%
36.9
51.3%
34.8
133.8%
21. Secondary Outcome
Title GMT of Anti-norovirus GI.1 VLP Antibody Titers (Pan-Ig ELISA)
Description GMT of anti-norovirus GI.1 VLP antibody titers measured by Pan-Ig ELISA are reported.
Time Frame Baseline (Day 1), Days 8, 29, 36, 57, 211 and 393

Outcome Measure Data

Analysis Population Description
PPS included all participants in the FAS, who received the planned vaccination (both doses of vaccine, i.e. NoV VLP vaccine or placebo), and did not have major protocol violations. Number analyzed is the number of participants with evaluable data at the given time point.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 72 67 66 66 24
Baseline (Day 1)
661.8
906.1
838.5
619.7
460.3
Day 8
678.0
4534.9
829.4
6382.8
455.2
Day 29
668.2
7701.1
791.9
8951.5
574.0
Day 36
4158.6
7663.6
6411.8
9161.1
7603.5
Day 57
6183.5
7235.1
8838.3
8182.2
8165.5
Day 211
3945.2
5161.2
5406.6
4882.3
3523.2
Day 393
2903.4
3672.1
3862.9
3370.0
2252.6
22. Secondary Outcome
Title GMT of Anti-norovirus GII.4 VLP Antibody Titers (Pan-Ig ELISA)
Description GMT of anti-norovirus GII.4 VLP antibody titers measured by Pan-Ig ELISA are reported.
Time Frame Baseline (Day 1), Days 8, 29, 36, 57, 211 and 393

Outcome Measure Data

Analysis Population Description
PPS included all participants in the FAS, who received the planned vaccination (both doses of vaccine, i.e. NoV VLP vaccine or placebo), and did not have major protocol violations. Number analyzed is the number of participants with evaluable data at the given time point.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 72 67 66 66 24
Baseline (Day 1)
761.9
1054.9
1066.3
897.4
1023.2
Day 8
766.6
4725.5
1078.9
5691.9
1054.6
Day 29
766.8
8105.1
1017.7
8314.1
1022.4
Day 36
4587.6
7911.9
5411.9
8025.5
10084.9
Day 57
6564.1
7489.2
7877.2
7028.4
9507.3
Day 211
3702.0
4915.8
4657.8
4456.2
4531.5
Day 393
2216.7
3151.5
2807.4
2853.9
2969.5
23. Secondary Outcome
Title GMFR of Anti-norovirus GI.1 VLP Antibody Titers (Pan-Ig ELISA)
Description GMFR of anti-norovirus GI.1 VLP antibody titers measured by Pan-Ig ELISA are reported. The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level.
Time Frame Days 8, 29, 36, 57, 211 and 393

Outcome Measure Data

Analysis Population Description
PPS included all participants in the FAS, who received the planned vaccination (both doses of vaccine, i.e. NoV VLP vaccine or placebo), and did not have major protocol violations. Number analyzed is the number of participants with evaluable data at the given time point.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 72 67 66 66 24
Day 8
1.0
5.1
1.0
10.3
1.0
Day 29
1.0
8.5
0.9
14.4
1.2
Day 36
6.3
8.5
7.6
14.8
17.3
Day 57
9.0
7.9
11.4
13.2
17.7
Day 211
6.0
5.8
6.4
7.9
8.0
Day 393
4.4
4.0
4.6
5.2
5.1
24. Secondary Outcome
Title GMFR of Anti-norovirus GII.4 VLP Antibody Titers (Pan-Ig ELISA)
Description GMFR of anti-norovirus GII.4 VLP antibody titers measured by Pan-Ig ELISA are reported. The fold rise was calculated as the ratio of the post-vaccination titer level to the pre-vaccination titer level.
Time Frame Days 8, 29, 36, 57, 211 and 393

Outcome Measure Data

Analysis Population Description
PPS included all participants in the FAS, who received the planned vaccination (both doses of vaccine, i.e. NoV VLP vaccine or placebo), and did not have major protocol violations. Number analyzed is the number of participants with evaluable data at the given time point.
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 72 67 66 66 24
Day 8
1.0
4.5
1.0
6.3
1.0
Day 29
1.0
7.7
1.0
9.3
1.0
Day 36
6.0
7.5
5.0
8.9
9.6
Day 57
8.7
6.9
8.3
7.8
9.3
Day 211
4.9
4.6
4.5
5.0
4.7
Day 393
3.1
3.1
2.6
3.0
3.1
25. Secondary Outcome
Title Percentage of Participants With At Least One Adverse Event of Special Interest (AESI)
Description 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.
Time Frame From first vaccination up to Day 393

Outcome Measure Data

Analysis Population Description
SAF included all participants who received at least 1 dose of vaccine (NoV VLP vaccine or placebo).
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 76 74 72 72 25
Number [percentage of participants]
1.3
1.7%
2.7
3.6%
2.8
3.9%
0.0
0%
0.0
0%
26. Secondary Outcome
Title Percentage of Participants With At Least One Adverse Event (AE) Leading to Participant's Withdrawal From the Study
Description Withdrawal due to an AE will occur if the participant experiences an AE that requires early termination of treatment, 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 From first vaccination up to Day 393

Outcome Measure Data

Analysis Population Description
SAF included all participants who received at least 1 dose of vaccine (NoV VLP vaccine or placebo).
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
Measure Participants 76 74 72 72 25
Number [percentage of participants]
1.3
1.7%
1.4
1.9%
0.0
0%
1.4
1.9%
0.0
0%

Adverse Events

Time Frame All-Cause Mortality and Serious adverse events: From first vaccination (Day 1) through end of study (Day 393); Other adverse events: From any vaccination (Day 1 and Day 29) up to 28 days post vaccination.
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. SAF included all participants who received at least 1 dose of vaccine (NoV VLP vaccine or placebo).
Arm/Group Title Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Arm/Group Description Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, intramuscularly (IM), on Day 1, followed by norovirus (NoV) GI.1 (15 μg)/GII.4 (50 μg) bivalent virus-like particle (VLP) vaccine (Formulation A), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Days 1 and 29. Participants ≥ 60 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg monophosphoryl lipid A (MPL) (Formulation B), IM, on Day 29. Participants ≥ 60 years of age, 2-dose regimen: Norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine with 15 μg MPL (Formulation B), IM, on Days 1 and 29. Participants 18 to 49 years of age, 1-dose regimen: Norovirus bivalent placebo-matching vaccine, IM, on Day 1, followed by norovirus GI.1 (15 μg)/GII.4 (50 μg) bivalent VLP vaccine (Formulation A), IM, on Day 29.
All Cause Mortality
Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1/76 (1.3%) 1/74 (1.4%) 0/72 (0%) 1/72 (1.4%) 0/25 (0%)
Serious Adverse Events
Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 7/76 (9.2%) 9/74 (12.2%) 17/72 (23.6%) 9/72 (12.5%) 0/25 (0%)
Blood and lymphatic system disorders
Haemorrhagic anaemia 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Cardiac disorders
Atrial fibrillation 1/76 (1.3%) 0/74 (0%) 2/72 (2.8%) 1/72 (1.4%) 0/25 (0%)
Aortic valve stenosis 1/76 (1.3%) 0/74 (0%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Cardiac failure congestive 0/76 (0%) 1/74 (1.4%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Acute coronary syndrome 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Acute myocardial infarction 0/76 (0%) 0/74 (0%) 0/72 (0%) 1/72 (1.4%) 0/25 (0%)
Aortic valve incompetence 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Atrial flutter 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Atrioventricular block complete 1/76 (1.3%) 0/74 (0%) 0/72 (0%) 0/72 (0%) 0/25 (0%)
Atrioventricular block second degree 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Myocardial infarction 1/76 (1.3%) 0/74 (0%) 0/72 (0%) 0/72 (0%) 0/25 (0%)
Stress cardiomyopathy 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Tachycardia 1/76 (1.3%) 0/74 (0%) 0/72 (0%) 0/72 (0%) 0/25 (0%)
Ear and labyrinth disorders
Vertigo positional 1/76 (1.3%) 0/74 (0%) 0/72 (0%) 0/72 (0%) 0/25 (0%)
Gastrointestinal disorders
Gastrointestinal haemorrhage 1/76 (1.3%) 0/74 (0%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Colitis 0/76 (0%) 0/74 (0%) 0/72 (0%) 1/72 (1.4%) 0/25 (0%)
Diarrhoea 0/76 (0%) 0/74 (0%) 0/72 (0%) 1/72 (1.4%) 0/25 (0%)
Diverticulum intestinal haemorrhagic 1/76 (1.3%) 0/74 (0%) 0/72 (0%) 0/72 (0%) 0/25 (0%)
Pancreatitis 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Pancreatitis acute 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
General disorders
Non-cardiac chest pain 1/76 (1.3%) 0/74 (0%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Complication associated with device 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Hepatobiliary disorders
Cholecystitis 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 1/72 (1.4%) 0/25 (0%)
Bile duct stone 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Infections and infestations
Pneumonia 0/76 (0%) 1/74 (1.4%) 0/72 (0%) 1/72 (1.4%) 0/25 (0%)
Sepsis 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 1/72 (1.4%) 0/25 (0%)
Urinary tract infection 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 1/72 (1.4%) 0/25 (0%)
Bronchitis 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Diverticulitis 0/76 (0%) 0/74 (0%) 0/72 (0%) 1/72 (1.4%) 0/25 (0%)
Escherichia sepsis 0/76 (0%) 0/74 (0%) 0/72 (0%) 1/72 (1.4%) 0/25 (0%)
Gastroenteritis viral 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Splenic abscess 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Streptococcal endocarditis 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Injury, poisoning and procedural complications
Hip fracture 0/76 (0%) 1/74 (1.4%) 2/72 (2.8%) 0/72 (0%) 0/25 (0%)
Cervical vertebral fracture 0/76 (0%) 1/74 (1.4%) 0/72 (0%) 0/72 (0%) 0/25 (0%)
Femur fracture 0/76 (0%) 1/74 (1.4%) 0/72 (0%) 0/72 (0%) 0/25 (0%)
Pelvic fracture 1/76 (1.3%) 0/74 (0%) 0/72 (0%) 0/72 (0%) 0/25 (0%)
Periprosthetic fracture 0/76 (0%) 1/74 (1.4%) 0/72 (0%) 0/72 (0%) 0/25 (0%)
Procedural pneumothorax 0/76 (0%) 0/74 (0%) 0/72 (0%) 1/72 (1.4%) 0/25 (0%)
Musculoskeletal and connective tissue disorders
Osteoarthritis 0/76 (0%) 1/74 (1.4%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Rotator cuff syndrome 0/76 (0%) 0/74 (0%) 0/72 (0%) 1/72 (1.4%) 0/25 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon 0/76 (0%) 0/74 (0%) 0/72 (0%) 1/72 (1.4%) 0/25 (0%)
Bone cancer 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Breast cancer 0/76 (0%) 0/74 (0%) 0/72 (0%) 1/72 (1.4%) 0/25 (0%)
Intraductal proliferative breast lesion 0/76 (0%) 1/74 (1.4%) 0/72 (0%) 0/72 (0%) 0/25 (0%)
Myelodysplastic syndrome 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Plasma cell myeloma 1/76 (1.3%) 0/74 (0%) 0/72 (0%) 0/72 (0%) 0/25 (0%)
Prostate cancer metastatic 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Nervous system disorders
Haemorrhagic stroke 0/76 (0%) 0/74 (0%) 0/72 (0%) 1/72 (1.4%) 0/25 (0%)
Metabolic encephalopathy 0/76 (0%) 0/74 (0%) 0/72 (0%) 1/72 (1.4%) 0/25 (0%)
Ruptured cerebral aneurysm 0/76 (0%) 0/74 (0%) 0/72 (0%) 1/72 (1.4%) 0/25 (0%)
Seizure 0/76 (0%) 1/74 (1.4%) 0/72 (0%) 0/72 (0%) 0/25 (0%)
Psychiatric disorders
Delirium 0/76 (0%) 1/74 (1.4%) 0/72 (0%) 0/72 (0%) 0/25 (0%)
Renal and urinary disorders
Acute kidney injury 1/76 (1.3%) 0/74 (0%) 0/72 (0%) 0/72 (0%) 0/25 (0%)
Bladder outlet obstruction 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma 0/76 (0%) 1/74 (1.4%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Acute respiratory failure 0/76 (0%) 0/74 (0%) 0/72 (0%) 1/72 (1.4%) 0/25 (0%)
Dyspnoea 0/76 (0%) 0/74 (0%) 0/72 (0%) 1/72 (1.4%) 0/25 (0%)
Pneumothorax 1/76 (1.3%) 0/74 (0%) 0/72 (0%) 0/72 (0%) 0/25 (0%)
Pulmonary embolism 0/76 (0%) 1/74 (1.4%) 0/72 (0%) 0/72 (0%) 0/25 (0%)
Vascular disorders
Deep vein thrombosis 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 1/72 (1.4%) 0/25 (0%)
Other (Not Including Serious) Adverse Events
Arm 1: NoV Vaccine Formulation A_1-Dose Arm 2: NoV Vaccine Formulation A_2-Dose Arm 3: NoV Vaccine Formulation B_1-Dose Arm 4: NoV Vaccine Formulation B_2-Dose Arm 5: NoV Vaccine Formulation A_1-Dose
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 28/76 (36.8%) 25/74 (33.8%) 23/72 (31.9%) 21/72 (29.2%) 7/25 (28%)
Gastrointestinal disorders
Dyspepsia 2/76 (2.6%) 0/74 (0%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Nausea 1/76 (1.3%) 1/74 (1.4%) 1/72 (1.4%) 0/72 (0%) 1/25 (4%)
Diarrhoea 4/76 (5.3%) 3/74 (4.1%) 2/72 (2.8%) 0/72 (0%) 0/25 (0%)
General disorders
Injection site bruising 4/76 (5.3%) 1/74 (1.4%) 4/72 (5.6%) 2/72 (2.8%) 0/25 (0%)
Fatigue 3/76 (3.9%) 3/74 (4.1%) 1/72 (1.4%) 3/72 (4.2%) 2/25 (8%)
Infections and infestations
Upper respiratory tract infection 8/76 (10.5%) 8/74 (10.8%) 5/72 (6.9%) 3/72 (4.2%) 1/25 (4%)
Viral upper respiratory tract infection 2/76 (2.6%) 4/74 (5.4%) 0/72 (0%) 1/72 (1.4%) 2/25 (8%)
Bronchitis 0/76 (0%) 1/74 (1.4%) 2/72 (2.8%) 2/72 (2.8%) 0/25 (0%)
Pneumonia 0/76 (0%) 0/74 (0%) 1/72 (1.4%) 2/72 (2.8%) 0/25 (0%)
Otitis media 0/76 (0%) 0/74 (0%) 0/72 (0%) 2/72 (2.8%) 0/25 (0%)
Conjunctivitis 0/76 (0%) 0/74 (0%) 0/72 (0%) 0/72 (0%) 1/25 (4%)
Injury, poisoning and procedural complications
Laceration 1/76 (1.3%) 2/74 (2.7%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Muscle strain 0/76 (0%) 2/74 (2.7%) 1/72 (1.4%) 0/72 (0%) 0/25 (0%)
Procedural pain 0/76 (0%) 1/74 (1.4%) 0/72 (0%) 2/72 (2.8%) 0/25 (0%)
Skin abrasion 2/76 (2.6%) 0/74 (0%) 0/72 (0%) 1/72 (1.4%) 0/25 (0%)
Contusion 0/76 (0%) 1/74 (1.4%) 1/72 (1.4%) 0/72 (0%) 1/25 (4%)
Exposure to communicable disease 0/76 (0%) 0/74 (0%) 0/72 (0%) 0/72 (0%) 1/25 (4%)
Musculoskeletal and connective tissue disorders
Back pain 2/76 (2.6%) 1/74 (1.4%) 1/72 (1.4%) 2/72 (2.8%) 0/25 (0%)
Pain in extremity 2/76 (2.6%) 0/74 (0%) 2/72 (2.8%) 2/72 (2.8%) 0/25 (0%)
Arthralgia 2/76 (2.6%) 1/74 (1.4%) 1/72 (1.4%) 1/72 (1.4%) 0/25 (0%)
Myalgia 1/76 (1.3%) 0/74 (0%) 3/72 (4.2%) 1/72 (1.4%) 0/25 (0%)
Muscle spasms 1/76 (1.3%) 0/74 (0%) 0/72 (0%) 2/72 (2.8%) 0/25 (0%)
Nervous system disorders
Headache 2/76 (2.6%) 2/74 (2.7%) 3/72 (4.2%) 1/72 (1.4%) 1/25 (4%)
Dizziness 1/76 (1.3%) 1/74 (1.4%) 3/72 (4.2%) 0/72 (0%) 0/25 (0%)
Presyncope 0/76 (0%) 0/74 (0%) 0/72 (0%) 2/72 (2.8%) 1/25 (4%)
Poor quality sleep 0/76 (0%) 0/74 (0%) 0/72 (0%) 0/72 (0%) 1/25 (4%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain 1/76 (1.3%) 1/74 (1.4%) 0/72 (0%) 2/72 (2.8%) 0/25 (0%)
Rhinorrhoea 0/76 (0%) 2/74 (2.7%) 0/72 (0%) 0/72 (0%) 0/25 (0%)
Vascular disorders
Hypertension 2/76 (2.6%) 0/74 (0%) 1/72 (1.4%) 1/72 (1.4%) 0/25 (0%)

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.

Results Point of Contact

Name/Title Medical Director
Organization Takeda
Phone +1-877-825-3327
Email trialdisclosures@takeda.com
Responsible Party:
Takeda
ClinicalTrials.gov Identifier:
NCT02661490
Other Study ID Numbers:
  • NOR-204
  • U1111-1162-4913
First Posted:
Jan 22, 2016
Last Update Posted:
May 18, 2020
Last Verified:
Apr 1, 2020