Influenza Virus Challenge for Flu

Overseen By Matthew J Memoli, M.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Antibiotics, Influenza treatments

Disqualifiers: Chronic pulmonary, cardiovascular, neurological, others

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

Compensation: Varies

Number of Visits: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial seeks to determine the smallest dose of the H10N7 flu virus that causes a mild to moderate infection in healthy individuals. By identifying this dose, researchers aim to use it in future flu vaccine tests. Participants will receive a nasal spray containing the virus and will be monitored closely to assess immune responses. Ideal candidates are healthy adults who do not smoke or use vaping products and are willing to stay in isolation for at least 10 days. 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 experience this novel approach.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, it does exclude individuals with certain medical conditions and those who have received specific treatments recently, so it's best to discuss your medications with the trial team.

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

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have a significant medical condition or are taking certain medications like long-term aspirin therapy, you may be excluded from participating.

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

Research has shown that the A/Mallard/Ohio-99/MM4/1989 H10N7 flu virus is "low pathogenicity," meaning it is less likely to cause severe illness. Researchers have used this virus to induce mild to moderate flu symptoms in healthy individuals, aiding in the understanding of immune responses to the flu.

In past studies, researchers aimed to determine a safe amount of this virus that could cause mild flu symptoms in most people without serious side effects. They focused on ensuring it was well-tolerated and did not cause severe reactions.

Although specific side effects are not detailed in the sources, the virus's low-risk nature suggests it is likely safe in a controlled setting. Participants in similar studies experienced mild to moderate symptoms, aligning with the study's goals. This information can help potential participants feel more informed about the virus's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about this treatment for the flu because it uses the A/Mallard/Ohio-99/MM4/1989 H10N7 virus, which is different from the strains usually found in common vaccines. Unlike the standard flu vaccines that target specific seasonal strains, this treatment offers a unique approach by using a non-seasonal influenza strain, potentially broadening the immune response. This novel method could lead to a more versatile defense against various influenza viruses, which is why it has caught the attention of the scientific community.

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

Research has shown that the A/Mallard/Ohio-99/MM4/1989 H10N7 flu virus can cause mild to moderate flu symptoms in people. Studies safely used the virus to induce these symptoms. This trial aims to understand how the immune system reacts to the virus. By determining the appropriate viral dose, future studies can assess vaccine efficacy. Previous trials demonstrated that the virus triggers an immune response, which is crucial for developing future treatments. ^{1 2 3 4 5}

Who Is on the Research Team?

Matthew J Memoli, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

Healthy adults aged 18-50 who can consent and agree to stay in isolation for at least 10 days without using tobacco, marijuana, or vaping. Women must meet specific fertility and HIV criteria; men must meet certain fertility conditions. Excludes those with significant medical issues, high-risk contacts, abnormal test results, recent illness or vaccinations, drug/alcohol abuse, psychiatric problems, non-English speakers.

Inclusion Criteria

Agrees to not use tobacco products, marijuana, or vaping products during participation

I am a woman following specific fertility and contraception guidelines and do not have HIV.

Able to provide consent

Exclusion Criteria

I have a serious long-term health condition like heart or lung disease.

I have a serious health condition like heart or lung disease, or I am immunocompromised.

I live with or am in close contact with high-risk individuals such as those over 65, under 5, or nursing home residents.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Inoculation and Monitoring

Participants are inoculated with one dose of the flu virus and monitored 24 hours a day in an isolation room for at least 10 days.

10 days

Continuous monitoring (in-patient)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with at least 4 follow-up visits over 8 weeks.

8 weeks

4 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• A/Mallard/Ohio-99/MM4/1989 H10N7

Trial Overview The trial is testing the smallest dose of H10N7 flu virus that causes mild to moderate infection in healthy people. This will help evaluate new flu vaccines' effectiveness. Participants will receive one dose via nasal spray and be monitored closely with frequent tests and symptom surveys.

How Is the Trial Designed?

Group I: 1 Experimental Treatment 1 Intervention

All participants receive challenge virus

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

The low pathogenic avian influenza virus (LPAI) H1N1 triggers a strong but very short-lived innate immune response in mallards, with key immune genes RIG-I and Mx significantly upregulated just one day after infection but returning to normal levels by day two.

This rapid response suggests that the mallard's immune system has evolved to effectively control LPAI infections while minimizing potential damage from prolonged immune activation, highlighting the importance of the spleen in this process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A rapid and transient innate immune response to avian influenza infection in mallards. Helin, AS., Wille, M., Atterby, C., et al.[2018]

A new H7N7 avian influenza vaccine candidate was developed using genes from low pathogenicity strains, showing broad antigenic cross-reactivity against various H7 subtype isolates, which is crucial for pandemic preparedness.

In preclinical studies, the vaccine demonstrated safety in mice and provided significant protection against mortality and lung infection from the H7N7 virus, leading to its advancement into phase-I human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of Eurasian H7N7/PR8 high growth reassortant virus for clinical evaluation as an inactivated pandemic influenza vaccine. Jadhao, SJ., Achenbach, J., Swayne, DE., et al.[2008]

The study investigated the pathogenesis of low-pathogenic avian influenza (LPAI) in Mallards, revealing that the infection primarily localized to the intestinal tract and cloacal bursa, with peak viral activity occurring around 2 days post-infection.

Exposure to the active metabolite of oseltamivir (Tamiflu) led to the development of a viral resistance mutation (H274Y) at certain concentrations, indicating potential challenges in treatment efficacy against LPAI in ducks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pathobiology and virus shedding of low-pathogenic avian influenza virus (A/H1N1) infection in mallards exposed to oseltamivir. Bröjer, C., Järhult, JD., Muradrasoli, S., et al.[2013]

The highly pathogenic avian influenza A(H5N2) virus clade 2.3.4.4 was found in a wild mallard in Alaska in August 2016, indicating its reoccurrence in North America.

This discovery suggests that the virus can persist at low frequencies in migratory bird populations, raising concerns about its potential spread during migration seasons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reoccurrence of Avian Influenza A(H5N2) Virus Clade 2.3.4.4 in Wild Birds, Alaska, USA, 2016. Lee, DH., Torchetti, MK., Killian, ML., et al.[2018]

The H10N7 avian influenza subtype caused outbreaks in Minnesota turkey farms in 1979 and 1980, with mortality rates reaching up to 31%, indicating a significant threat to poultry health.

The virus was found to be antigenically similar to strains isolated from healthy mallards nearby, suggesting that feral ducks may have introduced the virus to the turkey populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influenza A outbreaks in Minnesota turkeys due to subtype H10N7 and possible transmission by waterfowl. Karunakaran, D., Hinshaw, V., Poss, P., et al.[2007]

Laughing gulls infected with low-pathogenicity avian influenza viruses (LPAIVs) primarily shed the virus through their respiratory system, indicating a potential for direct bird-to-bird transmission.

In contrast, mallards infected with different LPAIVs shed the virus through both respiratory and fecal routes, suggesting that water contamination plays a significant role in the spread of these viruses among birds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-pathogenicity influenza viruses replicate differently in laughing gulls and mallards. Criado, MF., Moresco, KA., Stallknecht, DE., et al.[2021]

In a study comparing two strains of avian influenza A viruses in mink, the H10N4 strain (A/mink/Sweden/3,900/84) caused more severe respiratory lesions and greater viral replication compared to the H10N7 strain (A/chicken/Germany/N/49).

Mink infected with the H10N4 strain showed significant inflammatory reactions, lower weight gain, and higher levels of the virus in their tissues, indicating that this strain is more pathogenic in mink than the H10N7 strain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two avian H10 influenza A virus strains with different pathogenicity for mink (Mustela vison). Englund, L., Hård af Segerstad, C.[2019]

The study found that domestic mallards exposed to low pathogenic avian influenza virus (LPAIV) in a laboratory setting showed a stronger complement activity response in the first three days compared to sentinel and free-living mallards, indicating a robust initial immune reaction.

Despite differences in immune response strength, the innate humoral immune parameters measured suggest that domestic mallards can serve as a suitable model for studying the immune responses of free-living mallards, especially in cases of secondary exposure to LPAIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Comparative Study of the Innate Humoral Immune Response to Avian Influenza Virus in Wild and Domestic Mallards. van Dijk, JGB., Verhagen, JH., Hegemann, A., et al.[2020]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07215871

Rechallenge With a Low Pathogenicity Avian H10N7 ... The study hypothesis is that mild to moderate influenza disease (MMID) can be induced with the A/Mallard/Ohio/99/1989 H10N7 influenza challenge virus on re- ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05436444?term=DUCK&rank=5

Low Pathogenicity Avian H10N7 Influenza Virus in a ... This is a dose-finding and pathogenicity study following human challenge with a low pathogenicity avian influenza A H10N7. Participants will be inoculated with ...

3. trial.medpath.com trial.medpath.com/clinical-trial/99e77cfde4acfd88/nct07215871-h10n7-influenza-rechallenge-healthy-volunteers

Rechallenge With a Low Pathogenicity Avian H10N7 ... The study hypothesis is that mild to moderate influenza disease (MMID) can be induced with the A/Mallard/Ohio/99/1989 H10N7 influenza challenge ...

4. withpower.com withpower.com/trial/phase-1-influenza-human-6-2022-fb151?lat=36.65114&lng=-97.3517

Influenza Virus Challenge for Flu · Info for Participants The low pathogenic avian influenza virus (LPAI) H1N1 triggers a strong but very short-lived innate immune response in mallards, with key immune genes RIG-I ...

5. clinicaltrial.be clinicaltrial.be/fr/details/16348?per_page=100&only_recruiting=0&only_eligible=0&only_active=0

Low Pathogenicity Avian H10N7 Influenza Virus in a Health... This is a dose-finding and pathogenicity study following human challenge with a low pathogenicity avian influenza A H10N7. Participants will be ...