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

• ClinicalTrials.gov Identifier: NCT02868073
• Recruitment Status: Completed
• First Posted: August 16, 2016
• Last Update Posted: May 31, 2018
• Sponsor: Vaxart
• Information provided by (Responsible Party): Vaxart

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Norovirus Gastroenteritis	Biological: VXA-G1.1-NN (high dose) Oral Vaccine Tablet; Other: VXA Placebo Tablets; Biological: VXA-G1.1-NN (low dose) Oral Vaccine Tablet	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 66 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: 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
• Actual Study Start Date: July 29, 2016
• Actual Primary Completion Date: October 5, 2016
• Actual Study Completion Date: October 1, 2017

Arms and Interventions

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 Name: 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 Name: 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 Name: Placebo Control

Outcome Measures

Primary Outcome Measures :

1. Incidence of Treatment Emergent Solicited and Unsolicited Adverse Events [ Time Frame: Day 1 thru Day 28 ]
   Solicited Symptoms of Reactogenicity (thru Day 8); unsolicited Adverse Events thru Day 28 post vaccination

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 49 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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 -

Contacts and Locations

Locations

United States, Nebraska

Celerion, Inc.

Lincoln, Nebraska, United States, 68502

Sponsors and Collaborators

Vaxart

Investigators

• Principal Investigator: Laura Sterling, MD, PhD; Celerion

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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). pii: 121077. doi: 10.1172/jci.insight.121077.

• Responsible Party: Vaxart
• ClinicalTrials.gov Identifier: NCT02868073
• Other Study ID Numbers: VXA-G11-101
• First Posted: August 16, 2016
• Last Update Posted: May 31, 2018
• Last Verified: May 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Additional relevant MeSH terms:

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Vaccines; Immunologic Factors; Physiological Effects of Drugs