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

NCT ID: NCT02918006

Last Updated: 2022-10-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 179 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-08-31
• Study Completion Date: 2018-01-19

Brief Summary

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.

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).

Conditions

Influenza

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Oral Vaccine (VXA-A1.1)

Oral enteric coated vaccine tablets. Placebo (saline solution) IM injection will also be administered in this arm.

Group Type: EXPERIMENTAL

VXA-A1.1

Intervention Type: BIOLOGICAL

Enteric coated oral vaccine tablet

Saline Solution for Placebo IM Injection

Intervention Type: OTHER

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.

Group Type: ACTIVE_COMPARATOR

Fluzone®

Intervention Type: BIOLOGICAL

Fluzone Quadravalent (Fluzone®) influenza vaccine (QIV) suspension for intramuscular (IM) injection

Placebo Tablets

Intervention Type: OTHER

Placebo tablets similar in size, color and number to the active oral tablet vaccine drug product

Oral and IM Placebo

Two forms or placebos (saline IM injection and oral placebo tablets) will be administered in this arm.

Group Type: PLACEBO_COMPARATOR

Placebo Tablets

Intervention Type: OTHER

Placebo tablets similar in size, color and number to the active oral tablet vaccine drug product

Saline Solution for Placebo IM Injection

Intervention Type: OTHER

Interventions

VXA-A1.1

Enteric coated oral vaccine tablet

Intervention Type: BIOLOGICAL

Fluzone®

Fluzone Quadravalent (Fluzone®) influenza vaccine (QIV) suspension for intramuscular (IM) injection

Intervention Type: BIOLOGICAL

Placebo Tablets

Placebo tablets similar in size, color and number to the active oral tablet vaccine drug product

Intervention Type: OTHER

Saline Solution for Placebo IM Injection

Intervention Type: OTHER

Other Intervention Names

Oral H1N1 Ad5 Tableted Vaccine; Fluzone Quadravalent; Enteric Coated Placebo Tablets; 0.9% Sodium Chloride Injection, USP

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 49 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Biomedical Advanced Research and Development Authority

FED

Sponsor Role: collaborator

Vaxart

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sean Tucker, PhD

Role: STUDY_DIRECTOR

Vaxart, Inc.

Locations

WCCT Global

Costa Mesa, California, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 31978354 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33632249 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

VXA-CHAL-201

Identifier Type: -

Identifier Source: org_study_id