| Eligibility |
Inclusion Criteria:
1. Male or female between the ages of 18 - 49 years, inclusive
2. Able to give written informed consent
3. Healthy, as determined by the principal investigator (PI) or PI in consultation with
the research monitor and Sponsor Healthy = No clinically significant health concerns
or medical illness, as determined by medical history, physical examination, vital
signs, electrocardiogram (ECG), and clinical laboratories (complete blood count (CBC),
chemistry and urinalysis)
4. Comprehension of the study requirements with ability and willingness to complete all
assessments and comply with confinement period post viral challenge, and all scheduled
visits and contacts
5. Confirmed blood type (A or O)
6. Demonstrated to be H type-1 antigen secretor positive (by saliva test)
7. Body mass index between 17 and 35 kg/m2, inclusive, at Screening
8. Female participants must have a negative pregnancy test at pre-vaccination and
pre-challenge and fulfill one of the following Criteria:
1. At least one year post-menopausal;
2. Surgically sterile;
3. Use of oral, implantable, transdermal or injectable contraceptives for 30 days
prior to immunization and until 60 days after challenge;
i. A reliable form of contraception must be approved by the Investigator (eg, double
barrier method, Depo-Provera, intrauterine device, Norplant, oral contraceptives,
contraceptive patches) d. Not be sexually active (abstinent) or in a same sex
relationship (must be discussed with site staff and documented)
9. Male subjects must agree not to father a child or donate sperm, as well as to use
contraception/barrier (a male condom) or be abstinent from heterosexual intercourse,
from vaccination through the active period (Day 57)
Exclusion Criteria:
1. Administration/use of any investigational drug or device 30 days prior to vaccination
through the active period (Day 57)
2. Administration of any licensed vaccine within 30 days prior to vaccination or planned
use of the above stated during the active period (through Day 57)
3. Presence of a significant medical condition, which, in the opinion of the
investigator, precludes participation in the study. Significant medical condition =
for example, psychiatric conditions, or gastrointestinal disease, such as peptic
ulcer, symptoms or evidence of active gastritis or gastroesophageal reflux disease,
inflammatory bowel disease, alcohol or illicit drug abuse/dependency, or other
laboratory abnormalities
4. Laboratory values outside the range of normal for platelet counts and the following
coagulation tests: prothromibin time test (PT/INR), activated partial thromboplastine
time test (aPTT) and fibrinogen
5. Any of the following history or conditions that may lead to higher risk of clotting
events and/or thrombocytopenia:
1. Family or personal history of bleeding or thrombosis
2. History of heparin-related thrombotic events, and/or receiving heparin treatments
3. History of autoimmune or inflammatory disease
4. Presence of any of the following conditions known to increase risk of thrombosis
within 6 months prior to screening:
- Recent surgery other than removal/biopsy of cutaneous lesions
- Immobility (confined to bed or wheelchair for 3 or more successive days)
- Head trauma with loss of consciousness or documented brain injury
- Receipt of anticoagulants for prophylaxis of thrombosis
- Recent clinically significant infection
6. Any one of the following ECG findings within 45 days prior to vaccination:
Exclusionary ECG findings:
1. QTc F (interval duration > 450 msec (male) or > 470 msec (female)
2. QRS interval greater than 120 msec
3. PR interval greater than 220 msec
4. Clinically significant ST-T wave changes or pathologic Q waves
7. History of cancer or cancer treatment within past 3 years (excluding basal cell or
squamous cell carcinomas)
8. Presence of immunosuppression or medical condition possibly associated with impaired
immune responsiveness, including diabetes mellitus or angioedema
9. Donation or use of blood or blood products within 30 days prior to vaccination through
the active period (Day 57)
10. Diagnosed bleeding disorder or significant bruising or bleeding difficulties that
could make blood draws problematic
11. Any condition that resulted in the absence or removal of the spleen
12. Evidence of confirmed infection with human immunodeficiency virus (HIV), hepatitis B
surface antigen (HBsAg) or hepatitis C virus (HCV) with confirmatory assays
13. Abnormal stool pattern (fewer than 3 bowel movements per week or more than 3 per day)
14. History of irritable bowel disease or 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 (e.g. Celiac disease, gluten intolerance)
4. Pancreaticobiliary disorders
5. Irritable bowel syndrome
6. Inflammatory Bowel Disease
7. Surgical Resection with the exception of appendectomy or a minor resection that
is deemed acceptable by investigator and sponsor
8. Gastroesophageal reflux disease (GERD)
9. Hiatal Hernia
10. Peptic Ulcer (History of cholecystectomy is not exclusionary)
15. Use of proton pump inhibitors, H2 blockers or antacids within 7 days prior to
vaccination through the active period (Day 57)
16. Use of antibiotics within 30 days prior to vaccination through the active period (Day
57) Note: use of a brief (= 10 days) course of oral or topical antibiotic for minor
upper respiratory infection (URI), urinary tract infection (UTI), dental work, or skin
infection allowed within the screening period, but must be completed 7 days prior to
first vaccination
17. Use of medication known to affect the immune function (e.g. systemic corticosteroids
and others) within 14 days prior to vaccination through the active period (Day 57)
18. Regular use of nonsteroidal anti-inflammatory drugs within 7 days prior to vaccination
through the active period (Day 57)
19. Use of over-the-counter probiotics or antidiarrheals within 7 days prior to
vaccination through the active period (Day 57)
20. Evidence of recent (within 2 months of vaccination) or of current nonbacterial
gastroenteritis suggestive of NV infection [vomiting or unformed or watery stools (> 2
during a 24-hour period)]
21. Any gastroenteritis within the past 2 weeks prior to vaccination
22. Acute disease within 72 hours prior to vaccination, defined as the presence of a
moderate or severe illness with or without fever (as determined by the Investigator
through medical history and physical examination). (Assessment may be repeated during
screening period)
23. Presence of a fever = 38ºC measured orally at baseline
24. History if hematochezia (blood in stool) or melena (black stool)
25. Any significant hospitalization within the last year which in the opinion of the
investigator or sponsor could interfere with study participation
26. History of serious reactions to any vaccination such as anaphylaxis, respiratory
problems, Guillain-Barre syndrome, hives or abdominal pain
27. History of a hypersensitivity or allergic reaction to any component of the
investigational vaccine or placebo, including but not limited to fish gelatin.
Subjects with known fish allergies should be excluded.
28. History of drug, alcohol or chemical abuse within 1 year prior to vaccination
29. Positive test for drugs of abuse or alcohol at screening, vaccination baseline and
pre-challenge (except for previous marijuana use; concurrent or ongoing use of
marijuana during the active study period).
30. Consistent/habitual smoking within 2 months prior to vaccination (defined as smoking =
1 pack of cigarettes a day). Smoking is not permitted during the inpatient stay
31. Other conditions, in the clinical judgment of the investigator, that would jeopardize
the safety or rights of a subject or interfere with the evaluation of the study
Social/Occupational:
32. Living with or having daily contact with children < 5 years old or women known to be
pregnant or nursing; this includes significant contact at home, school, day-care, or
equivalent facilities
33. Living with or having daily contact with elderly persons > 70 years of age or
infirmed, diapered individuals, persons with disabilities or incontinence; this
includes at work or visits to nursing homes and day-care or equivalent facilities
34. Employment in the food service industry such as restaurant or cafeteria facilities;
specifically, this includes persons whose employment requires food handling and
processing in the 4 weeks following viral challenge
35. Health-care workers with patient contact expected in the 4 weeks following viral
challenge
36. Expected contact, via employment or at home, with immunocompromised persons in the 4
weeks following viral challenge. Immunocompromised persons = HIV-positive, receiving
immunosuppressive medications such as oral steroids, anti-neoplastic agents
37. Presence of household members who have received the Ad4 or Ad7 vaccines within 2
months prior to vaccination
38. Employment as an airline flight attendant or cruise ship crew, scheduled to work in
the 4 weeks following challenge
39. Persons planning to live in a confined environment (eg, a cruise, camp, etc.) in the 4
weeks following viral challenge
|
