Influenza Virus for Influenza

Recruiting at 1 trial location

Overseen By Nadine Rouphael, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Emory University

Must not be taking: Antivirals, NSAIDs, Steroids, Antihistamines

Disqualifiers: Pregnancy, Cardiovascular disease, Immunosuppression, others

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

Compensation: Varies

Number of Visits: 1

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the body's immune response to the flu and how the virus spreads, to improve vaccines and treatments. Researchers will use a specific flu strain, A/Texas/71/2017 (H3N2), to study these effects under controlled conditions. The trial will also assess the safety of exposing healthy participants to this flu strain. Individuals who are generally healthy and free from chronic illnesses like asthma or heart disease might be suitable candidates. Participants will be observed in a hospital setting and will receive compensation for their time. 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.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications that could affect the study, such as flu medications, aspirin, intranasal steroids, and some pain relievers, at least 14 days before the study and during the quarantine period, unless approved by the study investigator.

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

A previous study using the same flu virus strain reported no serious side effects from the time participants received the virus up to 29 days later. Researchers tested this specific flu virus, A/Texas/71/2017 (H3N2), to observe its effects on healthy adults. Some mild symptoms, similar to those of a regular flu, were observed, indicating that people might feel slightly unwell but not severely. Overall, healthy volunteers have tolerated the treatment well. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard flu treatments, which typically include antiviral medications like oseltamivir or zanamivir, this new approach uses a live influenza virus strain, specifically the Influenza A H3N2 strain. Researchers are excited because it explores a unique delivery method—an intranasal challenge or natural exposure—which could potentially induce a more natural immune response. This method might lead to better and longer-lasting immunity compared to traditional vaccines or antiviral drugs, offering a fresh perspective on flu prevention and treatment.

What evidence suggests that this treatment might be an effective treatment for the flu?

Research has shown that the A/Texas/71/2017 H3N2 flu virus strain is useful for understanding flu infections. In a controlled setting, this strain infected 78% of exposed individuals, demonstrating its high transmissibility. This strain is particularly interesting because it can evade some of the body's antibodies, which fight infections. This characteristic makes it ideal for studying the immune system's response to the flu. In this trial, participants will be exposed to the A/Texas/71/2017 H3N2 strain to gain insights into improving flu vaccines and treatments. ^{1 4 6 7 8}

Who Is on the Research Team?

Nadine Rouphael, MD

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

Healthy adults aged 18-49 in the metro Atlanta area can join this flu study. They must be willing to stay at Emory University Hospital for up to 12 days and attend follow-up visits. People with weak immune systems or certain medical conditions cannot participate.

Inclusion Criteria

Can understand and comply with all planned study procedures

Persons of childbearing potential must have a negative serum or urine pregnancy test at screening and a negative urine pregnancy test within 24 hours before challenge

Persons biologically able to become pregnant must be practicing abstinence or using an acceptable method of birth control for at least 30 days before the challenge through the duration of the trial

Exclusion Criteria

Have screening laboratory test results that are outside the laboratory reported normal values and deemed clinically significant by the study investigator

I have an active HIV, hepatitis B, or hepatitis C infection.

Persons who are breastfeeding or plan to breastfeed at any time during the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

8 weeks

1 visit (in-person)

Challenge and Observation

Participants receive the influenza virus via nasal spray or exposure to infected participants, followed by an 8-12 day inpatient stay for observation

2 weeks

Inpatient stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Outpatient visits at the Hope Clinic

What Are the Treatments Tested in This Trial?

Interventions

• Influenza A H3N2 strain

Trial Overview The trial is testing how a specific flu virus (A/Texas/71/2017 H3N2) affects the body and spreads. Participants will get the virus through a nasal spray or by being near infected people, while their immune response and transmission are studied.

How Is the Trial Designed?

Group I: Live Influenza Virus RG-A/Texas/71/2017 (H3N2 Experimental Treatment 1 Intervention

Participants will be pre-screened up to sixty days before the challenge study to identify baseline HAI titer. Participants will either be in the intranasal challenge or the natural exposure cohort.

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

NATIONAL PHILANTHROPIC TRUST

Collaborator

Trials

1

Recruited

50+

Published Research Related to This Trial

A new H3N2 influenza virus strain was identified in Germany from pigs showing flu symptoms, characterized by various tests and complete genome sequencing.

This strain is a reassortant, combining genes from both prevalent European porcine H3N2 and H1N2 viruses, indicating ongoing evolution and reassortment among swine influenza viruses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ongoing evolution of swine influenza viruses: a novel reassortant. Zell, R., Bergmann, S., Krumbholz, A., et al.[2008]

The study evaluated the effectiveness of various A/H3N2 vaccine strains over the past decade, finding that certain strains (PE/09, VI/11, TE/12) induced higher levels of neutralizing antibodies compared to others (HK/14, HK/19, CA/20), highlighting the importance of selecting effective vaccine strains.

Immunizing guinea pigs with three doses of monovalent vaccine stock resulted in stronger and broader neutralizing antibody responses against diverse circulating strains, suggesting that increasing the frequency of immunization could enhance protection against influenza A (H3N2).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Retrospective immunogenicity analysis of seasonal flu H3N2 vaccines recommended in the past ten years using immunized animal sera. Zhang, M., An, Y., Wu, X., et al.[2022]

A multidrug-resistant H3N2 influenza virus developed in an immunocompromised patient after just 5 days of oseltamivir treatment, showing a significant increase in resistance to this antiviral medication.

The virus exhibited a specific genetic change (a 4-amino acid deletion in the neuraminidase gene) that reduced sensitivity to oseltamivir and zanamivir, but it did not affect the virus's fitness or ability to spread, highlighting the challenges of treating influenza in vulnerable populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapid selection of a transmissible multidrug-resistant influenza A/H3N2 virus in an immunocompromised host. Memoli, MJ., Hrabal, RJ., Hassantoufighi, A., et al.[2021]

The 2002/2003 influenza season saw a moderate epidemic primarily caused by Influenza A (H3N2) and B viruses, with H3N2 dominating hospital isolates, indicating a need for effective monitoring and vaccination strategies.

A variant of H3N2, A/Fujian/411/02, was identified as a potential concern due to its poor reaction with the vaccine strain, suggesting a risk of vaccine mismatch for the upcoming season.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The 2002/2003 influenza season in the Netherlands and the vaccine composition for the 2003/2004 season]. de Jong, JC., Rimmelzwaan, GF., Bartelds, AI., et al.[2014]

Swine in Hong Kong carry H3N2 influenza A strains that are closely related to historical human strains, indicating that they may serve as a reservoir for both old and new variants of the virus.

The study used reciprocal hemagglutination inhibition tests and neuraminidase inhibition tests to confirm the relationships between swine and human strains, highlighting the potential for swine to contribute to influenza virus evolution and transmission to humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Further studies of the antigenic properties of H3N2 strains of influenza A isolated from swine in South East Asia. Shortridge, KF., Cherry, A., Kendal, AP.[2006]

The study identified two antigenically distinct groups of the H3N2 influenza virus, SW13 and HK14, that co-circulated during the 2014-2015 winter season, which is crucial for understanding the virus's evolution and its impact on public health.

Key mutations near the receptor-binding site on the hemagglutinin protein were found to significantly influence the antigenic variation of these H3N2 strains, providing valuable insights for future vaccine strain selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antigenic variation of the human influenza A (H3N2) virus during the 2014-2015 winter season. Hua, S., Li, X., Liu, M., et al.[2015]

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]

The H3N2 subtype of influenza A has been linked to severe flu seasons, with a notably low vaccine efficacy of only 28-42% during the 2016/2017 season against circulating strains.

H3N2 viruses have rapidly evolved since their introduction in 1968, developing genetic and antigenic changes that complicate vaccine effectiveness and virus characterization, including modifications to their hemagglutinin and neuraminidase proteins.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

H3N2 influenza viruses in humans: Viral mechanisms, evolution, and evaluation. Allen, JD., Ross, TM.[2019]

A study of 33 patients over three influenza seasons (2009-2011) in Quebec revealed significant antigenic drift in A/H3N2 viruses, indicating that the vaccine strains used were not well matched to circulating viruses, which can reduce vaccine effectiveness.

The research highlighted that while multiple mutations occurred in the HA gene, only a few strains showed significant antigenic drift, suggesting that both the number and specific locations of mutations are crucial in determining how the virus evolves and affects vaccine efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular and antigenic evolution of human influenza A/H3N2 viruses in Quebec, Canada, 2009-2011. Ann, J., Papenburg, J., Bouhy, X., et al.[2011]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11496904/

Controlled Human Influenza Virus Infection Model Studies ... This virus was found to have an attack rate of 78% when administered at a dose of 106 TCID50. The A/Texas/71/2017 H3N2 challenge virus and ...

2. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/54/NCT04978454/Prot_001.pdf

A Multicenter, Blinded, Randomized, Placebo-Controlled, ... This study is designed to determine the optimal infectious dose of the H3N2. (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus challenge ...

3. withpower.com withpower.com/trial/phase-1-influenza-human-7-2021-ac4d5

Influenza Challenge Study to Determine the Optimal ... The Influenza RG-A/Texas/71/2017 (H3N2) Challenge treatment is unique because it involves a specific H3N2 strain that has evolved to escape antibodies elicited ...

4. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1155880/full

H3N2 influenza hemagglutination inhibition method ... We report on a qualified and adaptable influenza serology method and analysis strategy to measure quantifiable HAI titers to define correlates of vaccine ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0264410X2500996X

Qualification of a reporter virus microneutralization assay ... Influenza vaccines help reduce influenza associated morbidity and mortality, but vaccine effectiveness estimates range from 10 %–60 % by season, with lower ...

6. ctv.veeva.com ctv.veeva.com/study/influenza-challenge-study-to-determine-the-optimal-infection-dose-and-safety-of-a-recombinant-h3n2

Influenza Challenge Study to Determine the Optimal Infection ... The primary objectives are: 1) To determine the optimal infectious dose of a recombinant influenza virus (A/Texas/71/2017 (H3N2), clade 3C3a) ...

7. ogtr.gov.au ogtr.gov.au/sites/default/files/2024-12/dir210_risk_assessment_and_risk_management_plan_consultation_version.docx

dir210_risk_assessment_and_ris... ... RG-A/Texas/71/2017 (H3N2). The study did not report any serious adverse effects (SAEs) from day 1 to day 29. However, some mild effects were observed ...

8. trial.medpath.com trial.medpath.com/clinical-trial/2541eed05acb8201/nct06972810-h3n2-influenza-virus-study-australia

Human Infection Study of H3N2 Influenza in Healthy Adults | MedPath This study will examine how the immune system responds to a flu virus (H3N2) during and after infection in health adults aged between 18 and 50 while in an ...