Bivalent Norovirus Vaccine Study
Condition: Gastroenteritis
MeSH terms: Gastroenteritis
Intervention: NoV GI.1/GII.4 Bivalent VLP Vaccine; Saline
Intervention description: 2 Doses 28 days apart Cohort A: 18-49 Years
Cohort A1: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (5/5 mcg)
Cohort A2: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (15/15 mcg)
Cohort A3: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg)
Cohort A4: IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (150/150 mcg)
Cohort B: 50-64 Years IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg)
Cohort C: 65-85 Years IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg)
Cohort D: 18-49 Years IM Norovirus Bivalent GI.1/GII.4 VLP Vaccine (50/50 mcg); Two doses 28 days apart
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 102.0
Sex: All
Minimum age: 18 Years
Maximum age: 85 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Vaccine, norovirus, acute gastroenteritis

Summary:

      Randomized, multi-site, dose-escalation study of the safety and immunogenicity of four dosage
      levels of Intramuscular (IM) Norovirus Bivalent VLP Vaccine adjuvanted with MPL and Al(OH)3
      compared to controls. Participants will receive two doses, by IM injection, 28 days apart.

      The hypotheses for this study are:

        -  The incidence of adverse events after vaccination with IM Norovirus Bivalent VLP Vaccine
           will be similar to the incidence of adverse events after other IM vaccines including
           CERVARIX® which contains MPL and Al(OH)3.

        -  Two doses of IM Norovirus Bivalent VLP Vaccine will be more immunogenic than one dose.

        -  The post-vaccination serum antibody responses, the number of antibody secreting cells
           (ASC), including homing markers, and memory B-cell responses directed against norovirus
           antigens will be increased after IM Norovirus Bivalent VLP Vaccine compared to controls.
    

Eligibility criteria:

        Inclusion Criteria:

        Participants must meet all of the inclusion criteria listed below:

          1. Signed written informed consent.

          2. Age:

               -  Cohort A: 18-49 years, inclusive

               -  Cohort B: 50-64 years, inclusive

               -  Cohort C: 65-85 years, inclusive

               -  Cohort D: 18-49 years, inclusive

          3. Health Status:

               -  Cohort A and D: In good health as determined by a screening evaluation that
                  includes vital signs, medical history, and physical exam within 45 days before
                  administration of IM Norovirus Bivalent VLP Vaccine or control.

               -  Cohorts B and C: In good health as determined by a screening evaluation that
                  includes vital signs, medical history, and physical exam within 45 days before
                  administration of IM Norovirus Bivalent VLP Vaccine or control. Any existing
                  medical diagnoses or conditions must be stable based on medical history and
                  targeted physical examination. A stable medical condition is defined as: (A)
                  Clinically acceptable health outcomes for the specific condition over the prior 6
                  months and (B) No change in prescription medication(s), dose, or frequency over
                  the prior 3 months. Acceptable changes in medications are: a change of health
                  care provider or insurance company or that is made for financial reasons as long
                  as the medications are in the same class and/or a change due to improvement in a
                  disease outcome.

          4. Expressed interest and availability to fulfill the study requirements.

          5. Female participants must be of non-childbearing potential (surgically sterile or
             post-menopausal for greater than or equal to [>=] 12 months), or if of childbearing
             potential (as determined by the investigator) must be practicing abstinence or using
             an effective licensed method of birth control (example oral contraceptives; diaphragm
             or condom in combination with contraceptive jelly, cream, or foam; intrauterine
             contraceptive device, or Depo-Provera; skin patch; vaginal ring or cervical cap) for
             30 days prior to vaccination and must agree to continue such precautions for at least
             60 days after the last vaccination. A woman is eligible if she is monogamous with a
             male who has had a vasectomy. Male participants must agree not to father a child for
             at least 60 days after the last vaccination and to practice abstinence or use an
             effective method of birth control as noted above.

          6. Agrees not to participate in another clinical trial with an investigational product
             for the entire duration of the study one year after the last study dose that is 393
             days.

          7. Agrees to storage of unused clinical specimens for an indefinite period of time for
             future norovirus research or research on other gastrointestinal pathogens.

        Exclusion Criteria:

        Participants who meet any of the exclusion criteria at baseline will be excluded from study
        participation. The exclusion criteria are:

          1. History of any of the following medical illnesses:

               -  Diabetes

               -  Cancer (malignancy other than resolved/excised skin lesion)

               -  Heart disease (hospitalization for a heart attack, arrhythmia, or syncope)

               -  Unconsciousness (other than a single brief "concussion")

               -  Seizures (other than febrile seizures as a child less than [<] 5 years old)

               -  Recurrent infections (more than 3 hospitalizations for invasive bacterial
                  infections such as pneumonia or meningitis)

               -  Any condition associated with immunodeficiency or participants taking
                  immunosuppressant medication

               -  Neuroinflamatory or auto-immune disease

          2. Any current illness requiring daily medication other than the following:

               -  Cohort A and D: Vitamins, birth control, anti-hypertensive medication,
                  antihistamines or anti-depressant medication. The Principal Investigator (PI)
                  should consult with the Central Safety Monitor and/or the sponsor for any
                  clarification of medications allowable.

               -  Cohorts B and C: Vitamins, birth control, anti-hypertensive medication,
                  antihistamines or anti-depressant medication or any current illness requiring
                  daily medication other than as noted above in inclusion criteria 3. The PI should
                  consult with the Central Safety Monitor and/or the sponsor for any clarification
                  of medications allowable.

          3. Allergies or hypersensitivity to any component of the vaccine including MPL and
             Al(OH)3 adjuvants.

          4. Any clinically significant abnormality detected on physical examination, including:

               -  Murmur (other than a functional murmur)

               -  Focal neurological abnormality

               -  Hepatosplenomegaly

               -  Lymphadenopathy

               -  Jaundice

          5. Hypertension (Blood Pressure [BP] greater than [>] 140/90 millimeter of mercury [mm
             Hg] on two separate days)

          6. Any lab abnormality (per the site local laboratory), as listed below:

               -  Absolute Neutrophil Count (ANC) outside the normal range (may be repeated if
                  outside this limit)

               -  Total white blood cells (WBC) outside the normal range (may be repeated if
                  outside this limit)

               -  Hemoglobin outside the normal range (may be repeated if outside this limit)

               -  Platelet count outside the normal range (may be repeated if outside this limit)

               -  Blood urea nitrogen (BUN) > upper limit of normal (ULN) (may be repeated if
                  outside this limit)

               -  Creatinine > ULN (may be repeated if outside this limit)

               -  Glucose (fasting or random) outside the normal range (may be repeated if outside
                  this limit)

               -  Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) > ULN (may be
                  repeated if outside this limit)

          7. Positive serology for hepatitis C or Human Immunodeficiency Virus (HIV) antibody or
             hepatitis B surface antigen.

          8. For women of child bearing potential, positive serum pregnancy test within 14 days and
             urine pregnancy test within 24 hours of administering either dose of IM Norovirus
             Bivalent VLP Vaccine or control.

          9. Nursing mother.

         10. Temperature >100.4 degree Fahrenheit (F) or symptoms of an acute self-limited illness
             such as an upper respiratory infection or gastroenteritis within 3 days of
             administration of IM Norovirus Bivalent VLP Vaccine or control.

         11. Previous participation in a Norovirus vaccine or challenge study.

         12. Study site personnel or their family members.

         13. Significant history of psychiatric hospitalization, alcohol abuse, or illicit drug use
             in the prior 5 years.

         14. Completion of an investigational vaccine or drug study within 28 days before
             administration of IM Norovirus Bivalent VLP Vaccine or control.

         15. Have a history of receiving immunoglobulin or other blood product within the 3 months
             prior to vaccination in this study.

         16. Other condition that in the clinical judgment of the investigator would jeopardize the
             safety or rights of a participant participating in the trial, would render the
             participant unable to comply with the protocol or would interfere with the evaluation
             of the vaccine.