Clinical trial NCT04875676: Immunogenicity & Safety Study of Adenovirus Type 5 (AD5) Based Oral Norovirus Vaccines
Official title: A Phase 1b, Open-label, Boost-optimization Study of an Adenoviral- Vector Based Oral Norovirus Vaccine (VXA-G1.1-NN) Expressing GI.1 VP1 Administered Orally to Healthy Adult Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Norovirus Infections
Lead sponsor: Vaxart
Sponsor class: INDUSTRY
First posted: 2021-05-06
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: PREVENTION

Brief summary: To evaluate the immunogenicity of VXA-G1.1-NN with repeat-dose administration at Day 1 and varying boost schedules (Week 4, 8 or 12 post initial dose) in healthy adults aged 18-55, inclusive, and to assess the safety and tolerability of VXA- G1.1-NN with repeat-dose administration at varying boost schedules (Week 4, 8 or 12) in healthy adults aged 18-55, inclusive


Eligibility criteria: Inclusion Criteria:

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

Age

1. 18 to 55 years old inclusive at the time of signing the Informed Consent Form (ICF).

   Type of Participants
2. General good health, without significant uncontrolled medical illness, based on medical history, physical examination, vital signs, and clinical laboratories (CBC, chemistry, and urinalysis) as determined by the investigator in consultation with the Research Monitor and Sponsor
3. Body mass index (BMI) between 17 and 35 kg/m2 at screening
4. 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
5. Male or female participants Contraception use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

   a. Female participants must provide a negative pregnancy test at each required visit and fulfill one of the following criteria:
   * At least 1 year post-menopausal (defined as amenorrhea for ≥12 consecutive months prior to Screening without an alternative medical cause).
   * Women under 60 years will need to verify post-menopausal status via a follicle-stimulating hormone (FSH) test if another option to prevent potential pregnancy will not be utilized for 30 days prior to baseline vaccination and until 60 days after the last vaccination.
   * Surgically sterile
   * Use of oral, implantable, transdermal or injectable contraceptives for 30 days prior to initial vaccination and until 60 days after the last vaccination. The form of contraception must be approved by the Investigator
   * A reliable form of contraception must be approved by the Investigator (e.g., double barrier method, Depo-Provera, intrauterine device, Norplant, oral contraceptives, contraceptive patches).
   * Not be sexually active (abstinent) or be in a relationship with partner who is sterile (must be discussed with site staff and documented).

   Informed Consent
6. 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 received treatment for cancer, 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 1 and 2
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 any 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. Positive urine drug screen for drugs of abuse at screening
15. Positive breath or urine alcohol test at screening and baseline Prior/Concurrent Therapy
16. Receipt of a licensed vaccine within 14 days prior to baseline vaccination or planned administration during the study active period (4 weeks post each study vaccination).
17. 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
18. 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
19. Daily use of nonsteroidal anti-inflammatory drugs within 7 days prior to study drug administration or planned use during the active study period
20. Administration of any investigational vaccine, drug or device within 8 weeks preceding study drug administration (Day 1), or planned use within the duration of the study Other Exclusions
21. Donation or use of blood or blood products within 30 days prior to study drug administration or planned donation during the active study period
22. History of drug, alcohol or chemical abuse within 1 year of screening
23. History of hypersensitivity or allergic reaction to any component of the investigational vaccine, including but not limited to fish gelatin

Primary outcomes:
measure: Viral-capsid Protein 1 (VP1)-Specific Antibody Secreting Cells (ASC) by Enzyme-linked Immunospot (ELISpot) Assay
timeFrame: Day 1 (Initial Vaccination) through Day 8 post boost (Second Vaccination)
measure: Norovirus G1.1 Histo-blood Group Antigen (HBGA) Blocking Antibodies (BT50) Assay
timeFrame: Day 1 (Initial Vaccination) through Day 29 post boost (Second Vaccination)
measure: VP1 Serum Immunoglobin G (IgG) by Mesoscale Discovery (MSD) Assay
timeFrame: Day 1 (Initial Vaccination) through Day 29 post boost (Second Vaccination)
measure: Norovirus G1.1 Histo-blood Group Antigen (HBGA) Blocking Antibodies (BT50) Assay
timeFrame: Day 1 (Initial Vaccination) through Day 29 post boost (Second Vaccination)
Secondary outcomes:
measure: Solicited Symptoms of Reactogenicity
timeFrame: Day 1 (Vaccination) to Day 8 post each vaccination
Other outcomes:
measure: Unsolicited Adverse Events (AEs)
timeFrame: Day 1 (Vaccine) through 28 days following boost (Second Vaccination)
measure: Long-term Safety
timeFrame: Day 1 (Vaccine) through 6 months following boost (Second Vaccination)
Locations:
city: Cypress
country: United States
facility: WCCT Global, Inc.
state: California
Study officials:
affiliation: Icon, Inc.
name: Helen Paguntalan, MD
role: PRINCIPAL_INVESTIGATOR
References: