Phase 1 Placebo-controlled, Randomized Trial of an Adenoviral-vector Based Norovirus Vaccine

A Phase 1, Randomized, Double-Blind, Placebo-controlled, Dose-ranging Trial to Determine the Safety and Immunogenicity of an Adenoviral-vector Based Norovirus Vaccine (VXA-G1.1-NN) Expressing GI.1 VP1 and dsRNA Adjuvant Administered Orally to Healthy Volunteers

A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Trial to Determine the Safety and Immunogenicity of an Adenoviral-Vector Based Norovirus Vaccine (VXA-G1.1-NN) Expressing GI.1 VP1 and dsRNA Adjuvant Administered Orally to Healthy Volunteers

Study Overview

• Status: Completed
• Conditions: Norovirus Gastroenteritis
• Intervention / Treatment: Other: VXA Placebo Tablets; Biological: VXA-G1.1-NN (high dose) Oral Vaccine Tablet; Biological: VXA-G1.1-NN (low dose) Oral Vaccine Tablet

Detailed Description

The study will enroll 66 subjects in four cohorts. All subjects will receive a single administration of VXA-G1.1-NN at a low dose, a high dose or placebo.

Two sentinel groups will enroll 3 subjects each in an open-label manner (Cohorts 1 and 3) to receive VXA-G1.1-NN prior to enrolling either of the randomized, controlled cohorts (Cohorts 2 and 4). Within the double-blinded Cohorts (2 and 4), placebo subjects will receive the same number of tablets as the vaccine subjects in that Cohort. Subjects will be enrolled and dosed in the low dose groups prior to initiation of dosing in the high dose group.

Cohort 1: 3 subjects at low dose Cohort 2: 20 subjects at low dose and 10 placebo Cohort 3: 3 subjects at high dose Cohort 4: 20 subjects at low dose and 10 placebo

Subjects will be followed for 28 days post vaccination for preliminary immunogenicity. Subjects will continue to be followed for 1 year post-vaccination for long term safety.

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Lincoln, Nebraska, United States, 68502
      • Celerion, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 49 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female volunteers aged 18 - 49 years, inclusive
2. Able to give written informed consent
3. Healthy (no clinically significant health concerns)
4. Safety laboratory values within the following range criteria normal range
5. Body mass index between 17 and 35 at screening

Exclusion Criteria:

1. Receipt of any investigational norovirus vaccine within two years prior to study
2. Receipt of any investigational vaccine, drug or device within 8 weeks preceding vaccination
3. Administration of any licensed vaccine within 30 days prior to study
4. 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
5. History of drug, alcohol or chemical abuse within 1 year prior to vaccination
6. Presence of a fever ≥ 38oC measured orally at baseline
7. Stool sample with occult blood at screening -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: H1N1 (high dose) Oral Vaccine Tablet; Singe dose of orally administered VXA-G1.1-NN (high dose) Oral Vaccine Tablet. 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.	Biological: VXA-G1.1-NN (high dose) Oral Vaccine Tablet; The drug product will be provided as small white enteric-coated tablets. Multiple tablets will be administered to deliver the high dose.; Other Names: H1N1 (high dose) Oral Vaccine Tablet
EXPERIMENTAL: H1N1 (low dose) Oral Vaccine Tablet; Singe dose of orally administered VXA-G1.1-NN (low dose) Oral Vaccine Tablet. 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.	Biological: VXA-G1.1-NN (low dose) Oral Vaccine Tablet; The drug product will be provided as small white enteric-coated tablets. Multiple tablets will be administered to deliver the low dose.; Other Names: H1N1 (low dose) Oral Vaccine Tablet
PLACEBO_COMPARATOR: Placebo Tablets; Singe dose of VXA Placebo tablets. The placebo tablets are small off-white tablets that are similar in size and number to the active vaccine dose being delivered.	Other: VXA Placebo Tablets; The placebo will be provided as small white enteric-coated tablets that are similar in size and number to the active drug product tablets.; Other Names: Placebo Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment Emergent Solicited and Unsolicited Adverse Events	Solicited Symptoms of Reactogenicity (thru Day 8); unsolicited Adverse Events thru Day 28 post vaccination	Day 1 thru Day 28

Collaborators and Investigators

• Sponsor: Vaxart
• Investigators: Principal Investigator: Laura Sterling, MD, PhD, Celerion

Publications and helpful links

General Publications

• Kim L, Liebowitz D, Lin K, Kasparek K, Pasetti MF, Garg SJ, Gottlieb K, Trager G, Tucker SN. Safety and immunogenicity of an oral tablet norovirus vaccine, a phase I randomized, placebo-controlled trial. JCI Insight. 2018 Jul 12;3(13):e121077. doi: 10.1172/jci.insight.121077.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 29, 2016
• Primary Completion (ACTUAL): October 5, 2016
• Study Completion (ACTUAL): October 1, 2017

Study Registration Dates

• First Submitted: August 11, 2016
• First Submitted That Met QC Criteria: August 11, 2016
• First Posted (ESTIMATE): August 16, 2016

Study Record Updates

• Last Update Posted (ACTUAL): May 31, 2018
• Last Update Submitted That Met QC Criteria: May 29, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: VXA-G11-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO