A Phase 2 Influenza A Challenge Study Following Oral Administration of an H1N1 HA Ad-Vector Seasonal Flu Vaccine

Phase 2 Randomized, Controlled, Human Influenza A (H1N1) Challenge Study Following Administration of an Oral H1N1 HA Adenoviral-Vector Based Seasonal Influenza Vaccine and dsRNA Adjuvant to Healthy Adult Volunteers

A Phase 2 Randomized, Placebo- and Active-Controlled, Human Influenza A/California/04/2009 (H1N1) Challenge Study Following Administration of an Oral H1N1 Hemagglutinin (HA) Adenoviral-Vector Based Seasonal Influenza Vaccine and dsRNA Adjuvant (VXA-A1.1) to Healthy Adult Volunteers.

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: VXA-A1.1; Other: Saline Solution for Placebo IM Injection; Biological: Fluzone®; Other: Placebo Tablets

Detailed Description

This is a Phase 2 randomized, placebo- and active-controlled, two-part study in which healthy adult volunteers with low or undetectable pre-existing antibodies against A/California/7/2009(H1N1) pdm09-like virus will be challenged with an influenza A/H1N1 human challenge strain approximately 90 days after vaccination with a single dose of H1N1 HA Adenoviral-vector based seasonal influenza vaccine and dsRNA adjuvant (VXA-A1.1), an injectable QIV vaccine, and/or placebo.

An independent Safety Monitoring Committee (SMC) will oversee the safety of the study.

To accommodate the limited size of the isolation unit that will be utilized for the challenge and post-challenge sequestration period, subjects will move through the study (enrollment, vaccination and challenge) sequentially in a total of 6 cohorts. Each cohort will randomize 30 subjects to obtain approximately 25 subjects per cohort for the challenge phase. Subjects will be randomized in a ratio of 2:2:1 (VXA-A1.1: Quadrivalent Influenza Vaccine (QIV): Placebo.

The study will be conducted in two parts.

Part A: Subjects will be randomized in a double-blinded manner to receive a single administration of one of three treatment arms:

• Arm 1: VXA-A1.1 oral vaccine + placebo Intramuscular (IM)
• Arm 2: QIV (IM) injection + oral placebo
• Arm 3: Placebo IM injection + oral placebo

Subjects will return to the site for ~8 visits and be contacted remotely at defined time points to be followed for immunogenicity and safety during study Part A.

Part B: Subjects will be challenged with a wild-type influenza A H1 virus strain ~90 days following vaccination. Blood samples will be collected to evaluate immunogenicity. Subjects will remain in the isolation unit for 6 to 9 days post-challenge.

Following challenge, influenza symptoms and signs will be assessed during the sequestration period. Blood samples and nasopharyngeal swab samples will be collected. Vital signs will be measured every 4 hours during waking hours.

After release from the isolation unit subjects will return to the site 30 days post-challenge. Part B will continue for purposes of collecting long term safety follow-up (serious adverse events (SAEs), AEs of special interest (AESIs) and any new onset of chronic illness (NOCI) via phone contacts through 1 year post-vaccination (Day 365).

• Study Type: Interventional
• Enrollment (Actual): 179
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Costa Mesa, California, United States, 92626
      • WCCT Global

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:

1. Male or female volunteers aged 18 - 49 years, inclusive
2. Able to give written informed consent
3. Low pre-existing antibodies to the study vaccine
4. In general good health (no clinically significant health concerns)
5. Safety laboratory normal range or not clinically significant (NCS), with few exceptions
6. Body mass index (BMI) between 17 and 35
7. Comprehension of the study requirements with ability and willingness to complete all assessments and comply with scheduled visits and contacts
8. Female participants must have a negative pregnancy test at screening

Exclusion Criteria:

1. Receipt of any influenza vaccine within two years prior to study
2. Use of any investigational vaccine/adjuvanted vaccine within 8 weeks of study
3. Use of any investigational drug or device within 4 weeks of study
4. Use of any licensed vaccine within 30 days of study
5. Presence of significant uncontrolled medical or psychiatric illness within 3 months of study
6. Clinically significant and/or protocol defined ECG abnormality
7. Positive serology for HIV-1 or HIV-2, or HBsAg or HCV antibodies
8. Cancer, or treatment for cancer, within 3 years of study
9. History of drug, alcohol or chemical abuse within 1 year
10. Receipt of blood or blood products within 6 months of study
11. Donation of blood within 4 weeks of study
12. Presence of a fever ≥ 38ºC measured orally at baseline
13. Stool sample with occult blood at screening
14. Positive urine drug screen for drugs of abuse at screening
15. Positive breath or urine alcohol test at screening or baseline
16. Consistent/habitual smoking within 2 months prior to vaccination
17. History of serious reactions to any vaccination such as anaphylaxis, respiratory problems, Guillain-Barre syndrome, hives or abdominal pain
18. Asthma, bronchiectasis or chronic obstructive pulmonary disease
19. Any known allergy or intolerance to oseltamivir

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oral Vaccine (VXA-A1.1); Oral enteric coated vaccine tablets. Placebo (saline solution) IM injection will also be administered in this arm.	Biological: VXA-A1.1; Enteric coated oral vaccine tablet; Other Names: Oral H1N1 Ad5 Tableted Vaccine; Other: Saline Solution for Placebo IM Injection; Other Names: 0.9% Sodium Chloride Injection, USP
Active Comparator: QIV IM Injection; A commercially available QIV will be administered at the approved dose level as the active comparator. Oral placebo tablets will also be administered in this arm.	Biological: Fluzone®; Fluzone Quadravalent (Fluzone®) influenza vaccine (QIV) suspension for intramuscular (IM) injection; Other Names: Fluzone Quadravalent; Other: Placebo Tablets; Placebo tablets similar in size, color and number to the active oral tablet vaccine drug product; Other Names: Enteric Coated Placebo Tablets
Placebo Comparator: Oral and IM Placebo; Two forms or placebos (saline IM injection and oral placebo tablets) will be administered in this arm.	Other: Saline Solution for Placebo IM Injection; Other Names: 0.9% Sodium Chloride Injection, USP; Other: Placebo Tablets; Placebo tablets similar in size, color and number to the active oral tablet vaccine drug product; Other Names: Enteric Coated Placebo Tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Influenza-like Clinical Illness and Laboratory Confirmed Infection Post Challenge With a Homologous A Strain Influenza Virus	The clinical efficacy of VXA-A1.1 to protect against illness caused by the homologous A strain influenza virus with challenge 3 months following a single immunization in comparison to placebo and QIV. Participants were evaluated for clinical signs and symptoms of influenza as well as for viral shedding via PCR for confirmation of infection.	Clinical Illness and/or laboratory confirmed infection occurring following viral challenge at 3 months post vaccination

Collaborators and Investigators

• Sponsor: Vaxart
• Collaborators: Biomedical Advanced Research and Development Authority
• Investigators: Study Director: Sean Tucker, PhD, Vaxart, Inc.

Publications and helpful links

General Publications

• Liebowitz D, Gottlieb K, Kolhatkar NS, Garg SJ, Asher JM, Nazareno J, Kim K, McIlwain DR, Tucker SN. Efficacy, immunogenicity, and safety of an oral influenza vaccine: a placebo-controlled and active-controlled phase 2 human challenge study. Lancet Infect Dis. 2020 Apr;20(4):435-444. doi: 10.1016/S1473-3099(19)30584-5. Epub 2020 Jan 21.
• McIlwain DR, Chen H, Apkarian M, Affrime M, Bock B, Kim K, Mukherjee N, Nolan GP, McNeal MM. Performance of BioFire array or QuickVue influenza A + B test versus a validation qPCR assay for detection of influenza A during a volunteer A/California/2009/H1N1 challenge study. Virol J. 2021 Feb 25;18(1):45. doi: 10.1186/s12985-021-01516-0. Erratum in: Virol J. 2021 Mar 15;18(1):55.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2016
• Primary Completion (Actual): August 8, 2017
• Study Completion (Actual): January 19, 2018

Study Registration Dates

• First Submitted: September 26, 2016
• First Submitted That Met QC Criteria: September 26, 2016
• First Posted (Estimate): September 28, 2016

Study Record Updates

• Last Update Posted (Actual): October 6, 2022
• Last Update Submitted That Met QC Criteria: October 2, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Challenge; oral vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: VXA-CHAL-201

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

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