H3N2 Virus Challenge for Flu

Overseen By Project Manager

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Duke University

Must not be taking: Corticosteroids, Beta agonists, Biologics, others

Disqualifiers: Respiratory disease, Cardiovascular disease, Neurological conditions, Autoimmune disease, Immunodeficiency, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand the body's response to the flu using a specific strain of the H3N2 influenza virus (Influenza A/Texas/71/2017). Researchers will study breath and saliva samples to detect early signs of infection. Participants will receive either the virus or a harmless placebo nasally. This trial suits healthy adults who have not recently had the flu and do not have ongoing medical conditions. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Do I have to stop taking my current medications for the trial?

The trial requires participants to stop using certain prescription or over-the-counter medications within 7 days prior to and throughout the confinement period, unless approved by the investigator. The protocol does not specify all medications, so you should discuss your current medications with the study team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that the Influenza A/Texas/71/2017 (H3N2) virus used in this trial is generally safe. In past studies, over 70% of people exposed to this virus contracted the flu. Importantly, these studies did not report any serious side effects. Some mild effects, such as typical flu symptoms, were noted, but nothing severe occurred from day 1 to day 29 after exposure. This suggests that while participants might experience flu-like symptoms, healthy adults usually tolerate the virus well. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the Influenza A/Texas/71/2017 (H3N2) treatment because it involves a recombinant version of the H3N2 virus, which is different from traditional flu vaccines that use inactivated or weakened viruses. This approach could potentially stimulate a more robust immune response. Additionally, the specific dose used in this trial has shown an attack rate of over 70%, which suggests it could be highly effective in challenging the virus. This could lead to quicker and more comprehensive protection compared to existing flu vaccines.

What evidence suggests that this trial's treatments could be effective for early detection of H3N2 infection?

In this trial, participants will receive either the A/Texas/71/2017 (H3N2) flu virus or a sham product. Research has shown that the A/Texas/71/2017 (H3N2) flu virus, at a specific dose, infects about 78% of those exposed. This indicates that many people contract this flu strain upon contact. The A/Texas/71/2017 strain can evade detection by antibodies, proteins that help fight infections. This characteristic makes it valuable for studying how the flu virus bypasses the immune system. Understanding this virus's behavior can lead to improved flu vaccines and treatments. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

Healthy adults aged 18-45 who can give informed consent, follow study procedures, and stay inpatient for at least a week post-challenge. They must not be heavy smokers or have recent histories of alcoholism or drug abuse. Women should use contraception and not be pregnant.

Inclusion Criteria

Non-habitual smoker of tobacco, e-cigarettes or marijuana

Eligibility laboratory values within acceptable parameters

Body mass index (BMI) >18.5 and <40 kg/m2 at screening

Exclusion Criteria

History of a previous severe allergic reaction to any drug or biologic with generalized urticaria, angioedema, or anaphylaxis

I have received blood or blood products in the last 6 months.

I have not been in close contact with anyone with a suspected or confirmed respiratory virus in the last week.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

6 weeks

Confinement

Participants are admitted to the inpatient unit 2 days prior to inoculation and remain until approximately Day 8-10 post challenge. Daily collection of biological samples and clinical information occurs.

10-12 days

Daily visits (inpatient)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with additional follow-up for 3 weeks post confinement.

3 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Influenza A/Texas/71/2017 (H3N2)

Trial Overview

The trial is testing the body's response to a flu virus (H3N2) by comparing it with a placebo. Up to 40 volunteers will get either the virus or sham placebo intranasally. The goal is to find early infection markers through breath and saliva analysis.

How Is the Trial Designed?

Group I: Influenza A/Texas/71/2017 (H3N2) Experimental Treatment 1 Intervention

Recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus at 106 TCID50 dose. This dose has an attack rate of \>70%, and a good safety profile related to adverse events reporting. Each vial of virus stock and diluent will be individually labeled with the product name, description and caution statement.

Group II: Sham Product Placebo Group 1 Intervention

The viral stock diluent will be used as a sham inoculum, without the viral stock added. Each vial of sham will be labeled with the product name, description and caution statement.

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

Owlstone Ltd

Industry Sponsor

Trials

13

Recruited

4,700+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Darwin Biosciences

Collaborator

Trials

1

Recruited

30+

Published Research Related to This Trial

The effectiveness of the influenza A(H3N2) vaccine was found to be 36% in the 2016-2017 season and dropped to 14% in the 2017-2018 season, indicating a significant decrease in vaccine efficacy over time.

The study revealed that specific mutations in the virus, such as the T135K loss of glycosylation, and the impact of prior vaccination history can influence vaccine effectiveness, suggesting that these factors should be considered in future vaccine design.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza Vaccine Effectiveness by A(H3N2) Phylogenetic Subcluster and Prior Vaccination History: 2016-2017 and 2017-2018 Epidemics in Canada. Skowronski, DM., Leir, S., Sabaiduc, S., et al.[2022]

Influenza A(H3N2) strains from Alachua County, Florida, during the 2014-15 season were identified as belonging to the hemagglutinin gene clade 3C.2a, which may have implications for vaccine formulation.

The effectiveness of the influenza vaccine was lower during this season, particularly in children, although the overall severity of illnesses was milder compared to the previous season, with severe cases primarily affecting elderly patients with pre-existing health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hemagglutinin Gene Clade 3C.2a Influenza A(H3N2) Viruses, Alachua County, Florida, USA, 2014-15. Lednicky, JA., Iovine, NM., Brew, J., et al.[2023]

In the first year after the high-dose trivalent inactivated influenza vaccine (TIV-HD) was licensed for adults aged 65 and older, 606 reports were made to the Vaccine Adverse Event Reporting System (VAERS), with only 8.2% involving serious events, indicating a generally favorable safety profile.

While no new serious safety concerns were identified, there was a notable increase in reported gastrointestinal events after TIV-HD compared to the standard dose vaccine, suggesting the need for further investigation into this potential association.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postlicensure safety surveillance for high-dose trivalent inactivated influenza vaccine in the Vaccine Adverse Event Reporting System, 1 July 2010-31 December 2010. Moro, PL., Arana, J., Cano, M., et al.[2013]

During the 2016 influenza season, the U.S. saw low overall activity but a slight increase in positive test results and localized outbreaks of influenza A (H3N2) starting in late August.

Most influenza viruses detected during this period were similar to the vaccine components recommended for the 2016-17 Northern Hemisphere vaccine, indicating good alignment between circulating strains and the vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update: Influenza Activity - United States and Worldwide, May 22-September 10, 2016. Budd, A., Blanton, L., Kniss, K., et al.[2019]

The 2019-2020 Northern Hemisphere influenza vaccine, which includes the 3c3.A H3N2 strain, generates antibodies in ferrets and humans, but these antibodies show reduced effectiveness against the currently circulating 3c2.A1b H3N2 viruses.

The study highlights a significant mismatch between the vaccine strain and the circulating strains, suggesting that the vaccine may not provide optimal protection against the prevalent H3N2 viruses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antigenic assessment of the H3N2 component of the 2019-2020 Northern Hemisphere influenza vaccine. Gouma, S., Weirick, M., Hensley, SE.[2021]

The study estimated that there were approximately 2055 illnesses caused by the H3N2v virus in the U.S. from August 2011 to April 2012, indicating that the virus was more widespread than laboratory-confirmed cases suggested.

Using a multiplier model, the researchers found that the true burden of illness was significantly underestimated, with multipliers of 200 for children and 255 for adults, highlighting the need for improved surveillance and detection of H3N2v infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estimates of the number of human infections with influenza A(H3N2) variant virus, United States, August 2011-April 2012. Biggerstaff, M., Reed, C., Epperson, S., et al.[2021]

A study of 19 influenza A/H3N2 viruses from Mexico revealed that multiple viral lineages can co-circulate within the same season and persist between seasons, which raises the risk of genetic reassortment.

The research identified a new minor cluster of the virus, named Korea, and emphasized the importance of using both molecular and antigenic data for effective surveillance of influenza virus diversity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular epidemiology of influenza A/H3N2 viruses circulating in Mexico from 2003 to 2012. Escalera-Zamudio, M., Nelson, MI., Cobián Güemes, AG., et al.[2021]

A study of 1116 serum samples revealed that only 25% of individuals had cross-reactive antibodies against the novel H3N2v influenza virus, with children and older adults showing significant susceptibility.

The seasonal trivalent inactivated influenza vaccine (TIV) did not significantly enhance seroprotection, as less than 15% of vaccinated individuals showed a notable increase in antibody levels, indicating that a specific vaccine may be necessary if H3N2v spreads widely.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cross-reactive and vaccine-induced antibody to an emerging swine-origin variant of influenza A virus subtype H3N2 (H3N2v). Skowronski, DM., Janjua, NZ., De Serres, G., et al.[2022]

The 2012 trivalent inactivated influenza vaccine did not significantly prevent hospital admissions for confirmed influenza A(H3N2) infection, as shown in a study of 92 patients.

Vaccination status did not influence the length of hospital stay or the final clinical outcomes for patients infected with the H3N2 strain, indicating limited efficacy of the vaccine against this specific influenza virus.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lack of effect of seasonal trivalent influenza vaccine against influenza A(H3N2) infections in hospitalised patients in winter 2012. Buchanan, J., Buckley, C., Jennings, LC., et al.[2014]

The Instituto Butantan seasonal trivalent influenza vaccine (IB-TIV) was found to be safe, with the majority of adverse events following immunization (AEFI) being classified as non-serious, based on an analysis of 1,253 reported cases from 2013 to 2017.

Common AEFI included local pain and fever, with serious adverse events occurring in only 9.8% of cases, aligning with known safety profiles of similar vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety assessment of seasonal trivalent influenza vaccine produced by Instituto Butantan from 2013 to 2017. Gattás, VL., Braga, PE., Koike, ME., et al.[2020]

In 2015, there was a notable increase in allergy-related adverse events following immunization (AEFI) with the seasonal trivalent influenza vaccines, rising from 12% in 2014 to 25%, particularly among adults, although the overall risk-benefit of the vaccination program remained unchanged.

The reporting risk for allergy-related AEFI nearly doubled in 2015 compared to previous years, indicating a potential variability in vaccine reactogenicity linked to different influenza vaccine strains, highlighting the need for ongoing monitoring of vaccine safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allergic adverse events following 2015 seasonal influenza vaccine, Victoria, Australia. Clothier, HJ., Crawford, N., Russell, MA., et al.[2018]

Both paper-based and web-based surveys reported similar rates of local and systemic adverse events following influenza vaccination, indicating that the method of data collection does not significantly affect the safety outcomes reported.

The paper-based survey, which recruited participants through general practitioners, was more representative of the elderly population targeted for influenza vaccination, suggesting that combining recruitment methods could enhance the accuracy of safety monitoring during mass vaccination campaigns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of different collection methods for reported adverse events following pandemic and seasonal influenza vaccination. Kemmeren, J., Honsbeek, M., Dijkstra, F., et al.[2017]

A new TaqMan assay has been developed specifically for detecting H3N2 influenza viruses, with a high sensitivity that can detect as few as 16.5 standard DNA copies.

This assay is important as H3N2 viruses continue to circulate alongside the pandemic H1N1 strain, potentially becoming more prevalent in future influenza seasons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of seasonal H3N2 influenza A virus by type-specific TaqMan minor groove binder probe assay. Wang, R., Schwartzman, LM., Memoli, MJ., et al.[2021]

Two new strains of the H3N2 influenza A virus, A/swine/Oklahoma/65980/2017 and A/swine/Oklahoma/65260/2017, were identified from pig samples in the United States, indicating ongoing evolution of the virus in swine populations.

These findings highlight the importance of monitoring influenza viruses in animals, as they can potentially impact both animal and human health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complete Genome Sequences of Two Novel Human-Like H3N2 Influenza A Viruses, A/swine/Oklahoma/65980/2017 (H3N2) and A/Swine/Oklahoma/65260/2017 (H3N2), Detected in Swine in the United States. Zeller, MA., Li, G., Harmon, KM., et al.[2020]

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