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

NCT03125473 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: VXA-G11-102
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

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

Conditions

Norovirus Gastroenteritis

Outcome Measures

Primary Outcomes (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).

  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).

  Day 1 thru Day 57

Secondary Outcomes (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.

  Day 1 thru Day 180

Study Arms (4)

Dose Group 1

EXPERIMENTAL

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

Dose Group 2

EXPERIMENTAL

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

Dose Group 3

EXPERIMENTAL

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

Dose Group 4

EXPERIMENTAL

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

Interventions

VXA-G1.1-NN Oral Vaccine BIOLOGICAL

The drug product will be provided as small white enteric-coated tablets. Multiple tablets will be administered to deliver the high total doses.

Also known as: Active VXA-G.1.1-NN Oral Tablet Vaccine

Dose Group 1; Dose Group 2; Dose Group 3; Dose Group 4

Eligibility Criteria

• Age: 19 Years - 49 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female volunteers aged 19 - 49 years
• Able to give written informed consent.
• Healthy (no clinically significant health concerns), as determined by medical history, physical examination, 12-lead ECG, and vital signs at screening.
• Safety laboratory values within the following range criteria at screening or abnormal and not clinically significant as outlined within the clinical protocol
• Body mass index between 17 and 35 inclusively (kg/m2)
• Comprehension of the study requirements with ability and willingness to complete all assessments and comply with scheduled visits and contacts.
• Female participants must have a negative pregnancy test at baseline and fulfill one of the following criteria:
• At least one year post-menopausal;
• Surgically sterile;
• Willing to use oral, implantable, transdermal or injectable contraceptives for 30 days prior to and until 60 days after vaccination;
• A reliable form of contraception must be approved by the Investigator

You may not qualify if:

• Receipt of any investigational norovirus vaccine within past 2 years
• 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.
• Administration of any licensed vaccine within 30 days prior to vaccination.
• 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
• 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.
• Positive serology for HIV-1 or HIV-2, or HBsAg or HCV antibodies.
• Cancer, or treatment for cancer treatment, within past 3 years (excluding history of basal cell carcinoma, squamous cell carcinoma, or cervical cancer in situ).
• 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.
• Presence of immunosuppression or medical condition possibly associated with impaired immune responsiveness, including diabetes mellitus.
• 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.
• Presence of household members who have received the Ad4 or Ad7 vaccines within 2 months prior to vaccination.

Sponsors & Collaborators

• Vaxart: lead

Study Sites (1)

Celerion, Inc.

Lincoln, Nebraska, 68502, United States

Location

Study Officials

• Laura Sterling, MD

  Celerion

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 14, 2017
• First Posted: April 24, 2017
• Study Start: April 7, 2017
• Primary Completion: July 1, 2017
• Study Completion: May 6, 2018
• Last Updated: May 30, 2018

Record last verified: 2018-05

Locations

US (1)