Ph 1b: Safety & Immunogenicity of Ad5 Based Oral Norovirus Vaccine
Ph 1b: Safety & Immunogenicity of Ad5 Based Oral Norovirus Vaccine
A Phase 1b, multicenter, randomized, double-blind, placebo-controlled study to determine the
 safety and immunogenicity of an adenoviral-vector based oral norovirus vaccine expressing
 GI.1 VP1 administered orally to healthy older adult volunteers 55-80 years of age. The study
 is designed to assess the safety, tolerability, immunogenicity, and efficacy of 2 dose levels
 of vaccine with a 2-dose vaccination schedule (4 weeks apart) in healthy older adults (55 to
 80 years old)
A Phase 1b, multicenter, randomized, double-blind, placebo-controlled study to determine the
 safety and immunogenicity of an adenoviral-vector based oral norovirus vaccine expressing
 GI.1 VP1 administered orally to healthy older adult volunteers 55-80 years of age. The study
 is designed to assess the safety, tolerability, immunogenicity, and efficacy of 2 dose levels
 of vaccine with a 2-dose vaccination schedule (4 weeks apart) in healthy older adults (55 to
 80 years old).

 Subjects will we randomized in the study utilizing an age and dose escalation schedule. A
 Safety Monitoring Committee will provide oversight of the trial throughout the duration of
 the study.
Inclusion Criteria

 To be eligible for this study, participants must meet all the following:

 Age

 1. 55 to 80 years old inclusive at the time of signing the Informed Consent Form (ICF).

 Type of Participants

 2. In stable and good general health, without significant medical illness, based on
 medical history, physical examination and vital signs at screening

 3. Safety laboratory values within the following range criteria at screening:

 1. Laboratory value of < grade 1 elevation from normal or decrease from normal with
 no clinical significance (NCS) for alkaline phosphatase (ALP), alanine
 aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin,

 2. Laboratory value of < grade 1 from normal with no NCS for:

 -  decreased: albumin, magnesium, total protein and phosphorous

 -  elevated: amylase, BUN, CPK and creatine and;

 -  elevated or decreased: calcium, glucose, potassium and sodium;

 4. Body mass index (BMI) between 17 and 35 kg/m2 at screening

 5. Available for all planned visits and phone calls, and willing to complete all
 protocol- defined procedures and assessments (including ability and willingness to
 swallow multiple small enteric-coated tablets per study dose).

 Gender and Reproductive Considerations

 6. Male or female participants Female participants must provide a negative pregnancy test
 at screening and baseline or be at least one year post-menopausal or surgically
 sterile. Female participants of childbearing potential must be willing to use a
 reliable oral, implantable, transdermal or injectable contraceptive for 30 days prior
 to and until 60 days post last study drug administration. The form of contraception
 must be approved by the Investigator Contraception use by men should be consistent
 with local regulations regarding the methods of contraception for participants in
 clinical studies.

 Informed Consent

 7. Capable of giving signed informed consent which includes compliance with the
 requirements and restrictions listed in the ICF and in this protocol.

 Exclusion Criteria

 The participants must be excluded from participating in the study if they meet any of the
 following:

 Medical Conditions

 1. Presence of significant uncontrolled medical or psychiatric illness (acute or chronic)
 including institution of new medical/surgical treatment or significant dose alteration
 for uncontrolled symptoms or drug toxicity within 3 months of screening and
 reconfirmed at baseline

 2. Cancer, or treatment for cancer treatment, within past 3 years (excluding basal cell
 carcinoma or squamous cell carcinoma)

 3. Presence of immunosuppression or medical condition possibly associated with impaired
 immune responsiveness, including diabetes mellitus

 4. History of irritable bowel disease or other inflammatory digestive or gastrointestinal
 condition that could affect the distribution/safety evaluation of an orally
 administered vaccine targeting the mucosa of the small intestine.

 Such conditions may include but are not limited to:

 1. Esophageal Motility Disorder

 2. Malignancy

 3. Malabsorption

 4. Pancreaticobiliary disorders

 5. Irritable bowel syndrome

 6. Inflammatory Bowel Disease

 7. Surgical Resection

 8. GERD

 9. Hiatal Hernia

 10. Peptic Ulcer (History of cholecystectomy is not exclusionary)

 5. History of any form of angioedema

 6. History of serious reactions to vaccination such as anaphylaxis, respiratory problems,
 hives or abdominal pain

 7. Diagnosed bleeding disorder or significant bruising or bleeding difficulties that
 could make blood draws problematic

 8. Any condition that resulted in the absence or removal of the spleen

 9. Acute disease within 72 hours prior to vaccination defined as the presence of a
 moderate or severe illness (as determined by the Investigator through medical history
 and physical exam). (Assessment may be repeated during screening period.)

 10. Presence of a fever ≥ 38oC measured orally at baseline (Assessment may be repeated
 during screening period)

 11. Any significant hospitalization within the last year which in the opinion of the
 investigator or sponsor could interfere with study participation.

 12. Any other condition that in the clinical judgment of the investigator would jeopardize
 the safety or rights of a participant taking in the study, would render the
 participant unable to comply with the protocol or would interfere with the evaluation
 of the study endpoints

 Diagnostic Assessments

 13. Positive human immunodeficiency virus (HIV), Hepatitis B surface antigen (HBsAg) or
 hepatitis C virus (HCV) tests at the screening visit

 14. Stool sample with occult blood at screening

 15. Positive urine drug screen for drugs of abuse at screening

 16. Positive breath or urine alcohol test at screening and baseline

 17. Positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by
 reverse transcription polymerase chain reaction (RT-PCR) at screening and by SARS-
 CoV-2 Rapid Antigen Test at baseline. If Rapid Antigen Test is positive, the test can
 be repeated using RT-PCR at baseline. If retest by PCR is also positive, the subject
 is ineligible.

 Prior/Concurrent Therapy

 18. Receipt of a licensed vaccine within 14 days prior to baseline vaccination or planned
 administration during the study active period (Day 57)

 19. Use of antibiotics, proton pump inhibitors, H2 blockers or antacids within 7 days
 prior to study drug administration or planned use during the active study period (Day
 57)

 20. Use of medications known to affect the immune function (e.g., systemic corticosteroids
 and others) within 2 weeks before study drug administration or planned use during the
 active study period (Day 57)

 21. Daily use of nonsteroidal anti-inflammatory drugs within 7 days prior to study drug
 administration or planned use during the active study period (Day 57)

 22. Administration of any investigational vaccine, drug or device within 8 weeks preceding
 study drug administration, or planned use within the duration of the study

 Other Exclusions

 23. Donation or use of blood or blood products within 30 days prior to study drug
 administration or planned donation during the active study period (Day 57)

 24. History of drug, alcohol or chemical abuse within 1 year of screening

 25. History of hypersensitivity or allergic reaction to any component of the
 investigational vaccine, including but not limited to fish gelatin