Flu Challenge Study

Recruiting at 2 trial locations

Overseen By Nadine Rouphael, MD, MSc

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Emory University

Must not be taking: Antivirals, NSAIDs

Disqualifiers: Chronic pulmonary, cardiovascular, diabetes, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the immune system's response to the H3N2 flu virus and examines how the virus spreads. Researchers aim to determine the safety of this controlled exposure and to understand the range of symptoms. It suits healthy adults without serious health conditions such as asthma, heart disease, or diabetes in the past five years. Participants will experience mild to moderate flu symptoms, similar to real-life scenarios. 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?

Yes, you must stop taking certain medications that could impact the influenza challenge. This includes prescription or over-the-counter medications like oseltamivir, zanamivir, and others, starting 14 days before and during the quarantine period, unless approved by the investigator.

Will I have to stop taking my current medications?

The trial requires participants to stop using certain medications that could affect the flu challenge or symptoms, such as flu antivirals, aspirin, and some over-the-counter drugs, at least 14 days before and during the quarantine period. It's best to discuss your specific medications with the study investigator to see if they are allowed.

What prior data suggests that the H3N2 influenza challenge virus is safe for use in clinical research?

Research has shown that the H3N2 flu virus has been safely used in past studies. Researchers created it specifically for controlled research settings. In earlier studies, the virus caused mild to moderate flu symptoms in healthy volunteers, which were less severe than those from other flu strains, such as the H1N1 virus. This indicates that while participants might feel unwell, severe effects are rare. These findings confirm the virus's safety for use in human trials. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for the flu focus on alleviating symptoms or shortening the duration of illness after infection. However, the Influenza Virus Type A H3N2 Challenge is unique because it involves exposing participants to a controlled dose of the influenza virus itself. This method allows researchers to study the body's immune response in real-time, which can lead to a better understanding of how to prevent and treat the flu more effectively. Researchers are excited about this approach because it could pave the way for developing vaccines and treatments that are more precisely tailored to combat specific flu strains.

What evidence suggests that the Influenza A H3N2 Challenge Virus is effective for studying flu response?

Studies have shown that the H3N2 influenza virus is a common type of flu virus. Researchers have used this specific strain in controlled settings to understand its effects on the body and the immune system's response. In this trial, participants will be exposed to the H3N2 strain, A/Perth/16/2009, which has proven suitable for clinical research, as it can reliably cause mild to moderate flu symptoms. This exposure allows researchers to study the body's natural reaction to the virus, providing valuable insights into flu transmission and immune defense. While the study focuses on understanding the virus rather than testing treatments, the information gathered may help develop better flu prevention and treatment strategies in the future. ^{1 2 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 who can follow study procedures and are not pregnant, breastfeeding, or planning to become pregnant. They must use birth control if applicable, avoid certain medications before and during the trial, not smoke or use tobacco products, and have no chronic diseases like asthma or heart conditions.

Inclusion Criteria

Are able to understand and comply with all planned study procedures

I will not take certain medications that could affect flu study results for 14 days before and during the study.

Demonstrate knowledge and comprehension of the study by scoring ≥70% on a quiz of the study protocol and policies

Exclusion Criteria

I am in close contact with vulnerable individuals, including young children, pregnant women, elderly, or those with chronic conditions.

I have been on high-dose steroids for more than 2 weeks in the last 3 months.

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Challenge and Observation

Participants are exposed to the influenza virus and observed for symptoms

8-12 days

Inpatient stay at Emory University Hospital

Follow-up

Participants are monitored for safety and effectiveness after the challenge

Up to 12 weeks

Outpatient visits at the Hope Clinic of the Emory Vaccine Center

What Are the Treatments Tested in This Trial?

Interventions

• Influenza Virus Type A H3N2 Challenge

Trial Overview The trial is testing how people's immune systems respond to a controlled flu virus infection (H3N2 strain) and how this virus spreads in an environment. It aims to understand the body's defense mechanisms against flu and assesses the safety of exposing healthy individuals to this specific flu strain.

How Is the Trial Designed?

Group I: Influenza Challenge Model with Influenza A H3N2 Strain Experimental Treatment 1 Intervention

Participants exposed to a previously validated influenza challenge model with influenza A H3N2 strain (A/Perth/16/2009 H3N2).

Influenza Virus Type A H3N2 Challenge is already approved in United States, United Kingdom for the following indications:

Approved in United States as H3N2 Influenza Challenge Virus for:

• Research Use Only - Not for Therapeutic Use

Approved in United Kingdom as H3N2 Influenza Challenge Virus for:

• Research Use Only - Not for Therapeutic Use

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Published Research Related to This Trial

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 rise in influenza cases during the 2003-2004 season was primarily due to the circulation of the A(H3N2) virus, which showed high similarity to the reference strain A/Fujian/411/02, with only minor variations in some strains.

Resistance to the antiviral drug rimantadine was found in 14% of the isolated A(H3N2) strains, and a significant portion of patients (68.7%) showed an increase in antibodies against the A(H3N2) virus, indicating a low overall immunity in the population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Characterization of epidemic influenza virus A(H3N2) strains circulating in Russia in the 2003-2004 epidemic season]. Ivanova, VT., Burtseva, EI., Slepushkin, AN., et al.[2016]

In trials involving the H1N1 influenza A virus, infections were mild across all age groups, particularly in volunteers with low initial antibody levels, indicating a generally lower severity compared to other influenza subtypes.

The study also found that recombinant viruses with H3 hemagglutinin showed similar mild symptoms, suggesting that gene substitutions from H1N1 can attenuate the severity of H3N2 viruses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human trials with wild-type H1N1 and recombinant H3N2-H1N1 influenza A viruses of 1977-1978. Beare, AS., Kendal, AP., Cox, NJ., et al.[2021]

Outpatients with influenza A(H1N1)pdm09 were more likely to be hospitalized compared to those with A(H3N2), indicating a higher initial severity of illness, especially among younger patients with fewer comorbidities.

Despite higher hospitalization rates and ICU admissions for A(H1N1)pdm09, there were no significant differences in disease progression or all-cause mortality within 60 days of discharge among the different influenza types/subtypes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of the Outcomes of Individuals With Medically Attended Influenza A and B Virus Infections Enrolled in 2 International Cohort Studies Over a 6-Year Period: 2009-2015. Dwyer, DE., Lynfield, R., Losso, MH., et al.[2022]

The wild-type influenza A/Bethesda/MM1/H3N2 challenge virus was safely administered to 37 healthy volunteers, resulting in mild to moderate influenza disease in 32% of participants, indicating its potential for studying influenza pathogenesis and immunity.

Compared to the A(H1N1)pdm09 challenge virus, the H3N2 virus caused less severe disease and lower viral shedding, suggesting that preexisting immunity may play a significant role in limiting viral replication and symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Dose-finding Study of a Wild-type Influenza A(H3N2) Virus in a Healthy Volunteer Human Challenge Model. Han, A., Czajkowski, LM., Donaldson, 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]

This study successfully established a wild-type influenza A challenge model using a GMP-produced virus, marking the first such study in the U.S. in over a decade, which will aid in developing vaccines and treatments.

The optimal dose of the A(H1N1)pdm09 virus caused mild to moderate illness in 69% of participants, with viral shedding occurring before symptoms, highlighting the potential for individuals to spread the virus before they feel sick.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Validation of the wild-type influenza A human challenge model H1N1pdMIST: an A(H1N1)pdm09 dose-finding investigational new drug study. Memoli, MJ., Czajkowski, L., Reed, S., et al.[2018]

In 2011, a variant influenza virus (A(H3N2)v) caused 12 human cases, showing a mix of genes from swine, avian, and human sources, including a gene from the H1N1 pandemic virus.

The A(H3N2)v virus was found to be antigenically different from seasonal influenza viruses, suggesting that it may require a specific vaccine, similar to the proposed vaccine strain A/Minnesota/11/2010.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human infections with novel reassortant influenza A(H3N2)v viruses, United States, 2011. Lindstrom, S., Garten, R., Balish, A., et al.[2022]

During the peak of the 2009 H1N1 pandemic, 52% of hospitalized patients had a single respiratory virus, with pH1N1 being associated with more severe symptoms like fever, cough, and gastrointestinal issues compared to other viruses.

The mortality rate for patients with pH1N1 was higher (2.1%) than for those with other respiratory viruses (0.3%), indicating a greater risk associated with pH1N1 infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Distinguishing characteristics between pandemic 2009-2010 influenza A (H1N1) and other viruses in patients hospitalized with respiratory illness. Chan, PA., Mermel, LA., Andrea, SB., et al.[2021]

In a clinical study involving 29 healthy young adults, a dose-dependent increase in influenza symptoms was observed, with 75% of participants developing confirmed illness at the highest dose of the A/H1N1 virus.

The safety profile of the challenge was acceptable, as symptoms were primarily mild to moderate and mainly affected the upper airways, indicating that this model can be safely used to evaluate the efficacy of vaccines and antiviral treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterisation of a wild-type influenza (A/H1N1) virus strain as an experimental challenge agent in humans. Watson, JM., Francis, JN., Mesens, S., et al.[2018]

Citations

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A Dose-finding Study of a Wild-type Influenza A(H3N2) ... Table 2. Clinical Outcomes of Participants Receiving the Influenza A(H3N2) Challenge Virus. Dose, Total, Symptoms, Shedding, MMID. 104 TCID50, 4, 4 (100), 0, 0.

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NCT05332899 | Influenza Human Challenge Model This study examines how the immune system responds to the flu virus (H3N2) during and after infection and how the flu virus is transmitted in the ...

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Influenza vaccine outcomes: a meta-analysis revealing ... Despite higher infection rates, vaccination against H3N2 remains as highly effective as vaccination against H1N1 and IBV in reducing influenza- ...

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Interim Estimates of 2024–2025 Seasonal Influenza ... Effectiveness against influenza A(H3N2) was 51% (IVY) against influenza-associated hospitalization but was not statistically significant in ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0264410X24010909

Advancing influenza vaccines: A review of next-generation ... Influenza vaccination is also effective against severe outcomes, as evidenced by a 37% reduction in influenza-associated hospitalizations [51] ...

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Influenza A (H3N2) - an overview Influenza A H3N2 is a subtype of influenza virus that has been associated with repeated infections in certain populations, such as middle-aged adults, ...

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H3N2 influenza viruses in humans: Viral mechanisms ... During the 2016/2017 flu season, the H3N2 component of the influenza vaccine exhibited a poor protective efficacy (∼28–42%) against preventing infection of co- ...

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Influenza virus type A: Infectious substances pathogen ... Influenza A is susceptible to disinfectants including sodium hypochlorite (freshly made 1:10 dilution of bleach), 60 to 95% ethanol, 2% alkaline ...