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

Influenza Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02918006
• Other study ID #: VXA-CHAL-201
• Status: Completed
• Phase: Phase 2
• Start date: August 31, 2016
• Est. completion date: January 19, 2018

Study information

• Verified date: October 2022
• Source: Vaxart
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 179
• Est. completion date: January 19, 2018
• Est. primary completion date: August 8, 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 49 Years

Eligibility

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

Related Conditions & MeSH terms

• Influenza
• Influenza, Human

Intervention

Biological:
• VXA-A1.1
Enteric coated oral vaccine tablet
• Fluzone®
Fluzone Quadravalent (Fluzone®) influenza vaccine (QIV) suspension for intramuscular (IM) injection

Other:
• Placebo Tablets
Placebo tablets similar in size, color and number to the active oral tablet vaccine drug product
• Saline Solution for Placebo IM Injection

Locations

Country	Name	City	State
United States	WCCT Global	Costa Mesa	California

Sponsors (2)

Lead Sponsor	Collaborator
Vaxart	Biomedical Advanced Research and Development Authority

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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