Safety & Immunogenicity Study of Ad5 Based Oral Norovirus Vaccines (VXA-NVV-103)

A Ph 1b, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Safety and Immunogenicity Study of Adenoviral-vector Based Oral Norovirus Vaccines Expressing GI.1 or GII.4 VP1 With Monovalent or Bivalent Dosing

VXA-NVV-103 is a phase 1B Randomized, Double-Blind, Placebo-Controlled, Multi-Center Safety and Immunogenicity Study of Adenoviral-vector Based Oral Norovirus Vaccines Expressing GI.1 or GII.4 VP1 with Monovalent or Bivalent Dosing in Healthy Adult Volunteers. The study consists of 2 parts: Part 1 is the double-blinded portion where subjects will be randomized to one of two monovalent vaccine groups, bivalent vaccine group or placebo. Subjects will be followed for ~4 weeks post vaccination for safety and immunogenicity. Part 2 will consist of an open label booster vaccination for the bivalent treatment group ~4 months post initial vaccination. All subjects will be followed for long term safety for 1 year post initial vaccination.

Study Overview

• Status: Completed
• Conditions: Norovirus Infection
• Intervention / Treatment: Biological: VXA-G1.1-NN; Biological: Placebo Tablets; Biological: VXA-G2.4-NS

Detailed Description

VXA-NVV-103 is a phase 1B Randomized, Double-Blind, Placebo-Controlled, Multi-Center Safety and Immunogenicity Study of Adenoviral-vector Based Oral Norovirus Vaccines Expressing GI.1 or GII.4 VP1 with Monovalent or Bivalent Dosing in Healthy Adult Volunteers. The study consists of 2 parts with will enroll 86 subjects:

Part 1 - Double Blind Period: Post confirmation of eligibility subjects will be randomized in a double-blinded manner to one of four treatment arms. Treatment Group 1 will contain an open-label sentinel group of 6 subjects to be enrolled prior to initiation of subsequent treatment groups. After review of the safety data and confirmation the dose is well tolerated through Study Day 8, the rest of the study will proceed in a double-blinded, randomized fashion. The 6 sentinel subjects will not be part of the 16 subjects in Treatment Group 1 to be enrolled in the double-blinded placebo-controlled cohort; randomization will be 1:1:2:1 for Treatment Groups 1 through 4 respectively.

Study Design and Vaccine Groups

1. Monovalent GII.4 VXA-G2.4-NS (6 sentinels / 16 randomized)
2. Monovalent GI.1 VXA-G1.1-NN (16 randomized)
3. Bivalent GII.4/GI.1 VXA-G2.4-NS + VXA-G1.1-NN (32 randomized)
4. Placebo Tablets no vaccine (16 randomized)

Subjects will be followed for ~4 weeks post vaccination for safety and immunogenicity. The study database will be locked post completion of Day 29 visits.

Part 2 will consist of an open label booster vaccination for the bivalent treatment group ~4 months post initial vaccination. Subjects will be followed for safety and immunogenicity for ~4 weeks post the boost.

All subjects will be followed for long term safety for 1 year post initial vaccination.

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Rapid Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female between the ages of 18 to 49 years, inclusive
• General good health, without significant medical illness, based on medical history, physical examination, vital signs, and clinical laboratories
• Demonstrate comprehension of the protocol procedures and willingness to adhere to all visits and assessments
• Body mass index between 17 and 35 at screening
• Female subjects must have a negative pregnancy test at screening and before each vaccination and fulfill protocol specified criteria for adequate birth control.

Exclusion Criteria:

• Presence of a significant medical condition which in the opinion of the investigator precludes participation in the study
• History of cancer or cancer treatment within past 3 years
• Presence of immunosuppression or medical condition possibly associated with impaired immune responsiveness, including diabetes mellitus or angioedema
• Donation or use of blood/blood products within 4 weeks prior to vaccination
• Diagnosed bleeding disorder or significant bruising or bleeding difficulties that could make blood draws problematic.
• Any condition that resulted in the absence or removal of the spleen
• Positive HIV, HBsAg or HCV tests at the screening visit
• Use of antibiotics, proton pump inhibitors, H2 blockers or antacids within 7 days of vaccination
• Use of medications known to affect the immune function within 14 days of vaccination
• Use of NSAIDs, sulfonylureas, and angiotensin II blockers within 7 days of vaccination
• Evidence of recent or of current nonbacterial gastroenteritis suggestive of NV infection to any gastroenteritis within 2 weeks of vaccination
• History of drug, alcohol or chemical abuse within 1 year of screening or positive urine drug test at screening
• Consistent/habitual smoking within 2 months as per medical history
• History of hypersensitivity or allergic reaction to any component of the investigational vaccine or placebo
• Use of any investigational vaccine, drug or device within 8 weeks preceding vaccination, or planned use of the above stated for the duration of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Monovalent GI.1; Monovalent GI.1 tableted vaccine group	Biological: VXA-G1.1-NN; Monovalent GI.1 tableted vaccine; Other Names: GI.1 oral vaccine tablet; Biological: Placebo Tablets; Tablets matching in number and appearance to active vaccine doses; Other Names: Oral tablets for control arm
Experimental: Monovalent GII.4; Monovalent GII.4 tableted vaccine group	Biological: Placebo Tablets; Tablets matching in number and appearance to active vaccine doses; Other Names: Oral tablets for control arm; Biological: VXA-G2.4-NS; Monovalent GII.4 tableted vaccine; Other Names: GII.4 oral vaccine tablet
Experimental: Bivalent GI.1 and GII.4 vaccine group; Bivalent vaccine group consisting of co-administration of GI.1 and GII.4 vaccine	Biological: VXA-G1.1-NN; Monovalent GI.1 tableted vaccine; Other Names: GI.1 oral vaccine tablet; Biological: VXA-G2.4-NS; Monovalent GII.4 tableted vaccine; Other Names: GII.4 oral vaccine tablet
Placebo Comparator: Placebo; Placebo tablets	Biological: Placebo Tablets; Tablets matching in number and appearance to active vaccine doses; Other Names: Oral tablets for control arm

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Solicited Adverse Events	Comparison of rate of occurance and severity of Solicited Adverse Events observed between treatment groups	Day 1 (Vaccination) to 7 days post vaccination
Rate of Unsolicited Adverse Events	Comparison of the rate of occurrence and severity of unsolicited Adverse Events observed between treatment groups	Day 1 (Vaccination) to 28 days post vaccination
Immunogenicity - VP1 Specific IgA ASC	LS Mean difference in VP1 specific IgA ASC between vaccine and placebo group	Day 1 (vaccination) to 7 days post-vaccination
Immunogenicity - BT50 Assay	Difference in HBGA blocking antibodies (by blocking titer fifty assay [BT50]) between vaccine and placebo groups	Day 1 (vaccination) to 28 days post-vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunogenicity - VP1 specific serum IgG	LS Mean difference in VP1 specific serum IgG between vaccine and placebo groups	Day 1 (vaccination) to 7 days post-vaccination

Collaborators and Investigators

• Sponsor: Vaxart
• Investigators: Principal Investigator: Mary Beth Manning, MD, Rapid Medical Research

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2019
• Primary Completion (Actual): January 15, 2021
• Study Completion (Actual): April 1, 2021

Study Registration Dates

• First Submitted: March 28, 2019
• First Submitted That Met QC Criteria: March 29, 2019
• First Posted (Actual): April 1, 2019

Study Record Updates

• Last Update Posted (Actual): September 21, 2022
• Last Update Submitted That Met QC Criteria: September 19, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Caliciviridae Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: VXA-NVV-103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Study results will be summarized and presented by treatment arm comparisons. Individual subject data will not be shared with other researchers.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No