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Dose-Optimization Trial of VXA-G1.1-NN in Healthy Volunteers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03125473
Recruitment Status : Completed
First Posted : April 24, 2017
Last Update Posted : May 30, 2018
Sponsor:
Information provided by (Responsible Party):
Vaxart

Brief Summary:
A Phase 1b, randomized, double-blind, dose-ranging trial to determine the safety of different dosing regimens an adenoviral-vector based norovirus vaccine (VXA-G1.1-NN) expressing GI.1 VP1 and dsRNA adjuvant administered orally to healthy volunteers

Condition or disease Intervention/treatment Phase
Norovirus Gastroenteritis Biological: VXA-G1.1-NN Oral Vaccine Phase 1

Detailed Description:

This study will enroll approximately 60 subjects in four cohorts of 15 subjects each. The cohorts may be enrolled and run in parallel or overlap; they do not have to run sequentially. The dosing for each cohort will be as follows:

Cohort 1: Multiple low dose on Days 1 and 8 Cohort 2: Multiple low dose on Days 1, 3 and 5 Cohort 3: Multiple low dose on Days 1 and 29 Cohort 4: Multiple high dose on Days 1 and 29

All subjects receiving study drug will have safety and immunogenicity assessments completed through Study Day 57 following their initial vaccination. Subjects may also be evaluated for persistent immunogenicity at Day 180 and will be followed for safety for 12 months following initial vaccination (Study Day 365).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 66 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: A Phase 1b, Open-Label, Dose-Optimization Trial of an Adenoviral-vector Based Norovirus Vaccine (VXA-G1.1-NN) Expressing GI.1 VP1 and dsRNA Adjuvant Administered Orally to Healthy Volunteers
Actual Study Start Date : April 7, 2017
Actual Primary Completion Date : July 1, 2017
Actual Study Completion Date : May 6, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dose Group 1
Multiple doses of low dose VXA-G1.1-NN Oral Vaccine Tablets will be orally administered. VXA-G1.1-NN is an E1/E3-deleted replication-defective Adenovirus serotype 5 vaccine vector for prevention of noroviral gastroenteritis caused by Norovirus GI.1. The vaccine vector encodes for a full length VP1 (major capsid protein) gene from Norvirus GI.1 Norwalk. Subjects will receive 1 tablet of VXA-G1.1-NN on Days 1 and 8
Biological: VXA-G1.1-NN Oral Vaccine
The drug product will be provided as small white enteric-coated tablets. Multiple tablets will be administered to deliver the high total doses.
Other Name: Active VXA-G.1.1-NN Oral Tablet Vaccine

Experimental: Dose Group 2
Multiple doses of low doseVXA-G1.1-NN Oral Vaccine Tablets will be orally administered. VXA-G1.1-NN is an E1/E3-deleted replication-defective Adenovirus serotype 5 vaccine vector for prevention of noroviral gastroenteritis caused by Norovirus GI.1. The vaccine vector encodes for a full length VP1 (major capsid protein) gene from Norvirus GI.1 Norwalk. Subjects will receive 1 tablet of VXA-G1.1-NN on Days 1, 3, and 5
Biological: VXA-G1.1-NN Oral Vaccine
The drug product will be provided as small white enteric-coated tablets. Multiple tablets will be administered to deliver the high total doses.
Other Name: Active VXA-G.1.1-NN Oral Tablet Vaccine

Experimental: Dose Group 3
Multiple doses of low dose VXA-G1.1-NN Oral Vaccine Tablets will be orally administered. VXA-G1.1-NN is an E1/E3-deleted replication-defective Adenovirus serotype 5 vaccine vector for prevention of noroviral gastroenteritis caused by Norovirus GI.1. The vaccine vector encodes for a full length VP1 (major capsid protein) gene from Norvirus GI.1 Norwalk. Subjects will receive 1 tablet of VXA-G1.1-NN on Days 1 and 29.
Biological: VXA-G1.1-NN Oral Vaccine
The drug product will be provided as small white enteric-coated tablets. Multiple tablets will be administered to deliver the high total doses.
Other Name: Active VXA-G.1.1-NN Oral Tablet Vaccine

Experimental: Dose Group 4
Multiple doses of low dose VXA-G1.1-NN Oral Vaccine Tablets will be orally administered. VXA-G1.1-NN is an E1/E3-deleted replication-defective Adenovirus serotype 5 vaccine vector for prevention of noroviral gastroenteritis caused by Norovirus GI.1. The vaccine vector encodes for a full length VP1 (major capsid protein) gene from Norvirus GI.1 Norwalk. Subjects will receive 6 tablets of VXA-G1.1-NN on Days 1 and 29
Biological: VXA-G1.1-NN Oral Vaccine
The drug product will be provided as small white enteric-coated tablets. Multiple tablets will be administered to deliver the high total doses.
Other Name: Active VXA-G.1.1-NN Oral Tablet Vaccine




Primary Outcome Measures :
  1. Evaluate the safety of different dosing regimens of VXA-G1.1-NN vaccine as determined by the incidence of treatment-emergent adverse events, physical exams, vital signs, and clinical laboratory test results (hematology, serum chemistry, and urinalysis). [ Time Frame: Day 1 thru Day 57 ]
    Safety will be evaluated by local and systemic reactogenicity (solicited symptoms), and clinical and laboratory assessments including physical exams, vital signs, clinical laboratory tests (hematology, serum chemistry, and urinalysis), and adverse events (AEs).


Secondary Outcome Measures :
  1. Evaluate the effect of different dosing regimens of VXA-G1.1-NN vaccine on its immunogenicity as determined by cellular and humoral immune function assays performed on blood samples collected at preselected study visits. [ Time Frame: Day 1 thru Day 180 ]
    All subjects will have blood samples collected on study days 7, 28, and 57 following their initial vaccination for cellular and humoral immune function assays (i.e., production of vaccine specific blocking and neutralizing antibodies, formation of vaccine specific antibody secreting and memory cells, etc.) to assess the effect of the different dosing schedules on the immunogenicity of the VXA-G1.1-NN vaccine. Subjects may also be evaluated for persistent immunogenicity at Day 180 (optional).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   19 Years to 49 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Male or female volunteers aged 19 - 49 years
  2. Able to give written informed consent.
  3. Healthy (no clinically significant health concerns), as determined by medical history, physical examination, 12-lead ECG, and vital signs at screening.
  4. Safety laboratory values within the following range criteria at screening or abnormal and not clinically significant as outlined within the clinical protocol
  5. Body mass index between 17 and 35 inclusively (kg/m2)
  6. Comprehension of the study requirements with ability and willingness to complete all assessments and comply with scheduled visits and contacts.
  7. Female participants must have a negative pregnancy test at baseline and fulfill one of the following criteria:

    1. At least one year post-menopausal;
    2. Surgically sterile;
    3. Willing to use oral, implantable, transdermal or injectable contraceptives for 30 days prior to and until 60 days after vaccination;
    4. A reliable form of contraception must be approved by the Investigator

Exclusion Criteria:

  1. Receipt of any investigational norovirus vaccine within past 2 years
  2. Administration of any investigational vaccine, drug or device within 8 weeks preceding vaccination, or planned use of the above stated during the study through the 12-month safety follow-up.
  3. Administration of any licensed vaccine within 30 days prior to vaccination.
  4. Presence of significant uncontrolled medical or psychiatric illness (acute or chronic) including institution of new medical/surgical treatment or dose alteration for uncontrolled symptoms or drug toxicity within 3 months
  5. Any one of the following ECG findings within 30 days prior to vaccination:

    • QTcF interval duration > 460 msec (male) or > 470 msec (female),
    • QRS interval greater than 120 msec,
    • PR interval greater than 220 msec,
    • Clinically significant ST-T wave changes or pathologic Q waves.
  6. Positive serology for HIV-1 or HIV-2, or HBsAg or HCV antibodies.
  7. Cancer, or treatment for cancer treatment, within past 3 years (excluding history of basal cell carcinoma, squamous cell carcinoma, or cervical cancer in situ).
  8. 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.
  9. Presence of immunosuppression or medical condition possibly associated with impaired immune responsiveness, including diabetes mellitus.
  10. Administration of any medications or treatments that may adversely affect the immune system such as allergy injections, immune globulin, interferon, immunomodulators, cytotoxic drugs or other drugs known to be associated with significant major organ toxicity, or systemic corticosteroids (oral or injectable) during 3 months prior to vaccination. Inhaled and topical corticosteroids allowed.
  11. Presence of household members who have received the Ad4 or Ad7 vaccines within 2 months prior to vaccination.
  12. Presence of household members who are neonates, pregnant women, or hematopoietic stem cell transplant or solid organ transplant recipients from screening until the end of the active period
  13. History of drug, alcohol or chemical abuse within 1 year prior to vaccination.
  14. Receipt of blood or blood products 6 months prior to vaccination or planned administration during the follow-up study period.
  15. Donation of blood or blood products within 4 weeks prior to vaccination or planned donation during the study period.
  16. Acute disease within 72 hours prior to vaccination defined as the presence of a moderate or severe illness with or without fever.

    during screening period).

  17. Presence of fever ≥38oC
  18. Stool sample with occult blood
  19. Positive urine drug screen for drugs of abuse
  20. Positive urine alcohol test at
  21. Consistent/habitual smoking within 2 months prior to vaccination.
  22. History of serious reactions to any vaccination such as anaphylaxis, respiratory problems, hives or abdominal pain.
  23. Diagnosed bleeding disorder or significant bruising or bleeding difficulties that could make blood draws problematic.
  24. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03125473


Locations
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United States, Nebraska
Celerion, Inc.
Lincoln, Nebraska, United States, 68502
Sponsors and Collaborators
Vaxart
Investigators
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Principal Investigator: Laura Sterling, MD Celerion
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Responsible Party: Vaxart
ClinicalTrials.gov Identifier: NCT03125473    
Other Study ID Numbers: VXA-G11-102
First Posted: April 24, 2017    Key Record Dates
Last Update Posted: May 30, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs