Recombinant H3N2 for Flu

No longer recruiting at 3 trial locations

Overseen By Christopher Woods

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

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

Must not be taking: Corticosteroids, Immunosuppressants, Allergy injections, 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: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the safest and most effective dose of a specific strain of the flu virus, H3N2, for use in future vaccine or treatment studies. Researchers will administer this flu virus, known as Influenza RG-A/Texas/71/2017 (H3N2) Challenge, to healthy adults to observe their bodily reactions and track any symptoms. The trial suits healthy individuals who have not recently received a flu vaccine and do not have ongoing health issues. Participants will be monitored for flu symptoms and viral activity after receiving the virus.

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 novel treatment.

Will I have to stop taking my current medications?

The trial requires participants to stop using certain medications, such as specific antiviral drugs and over-the-counter medications like aspirin and NSAIDs, at least 7 days before and during the confinement period, unless approved by the investigator. If you are on other medications, it is best to discuss with the study team to see if they are allowed.

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

Research has shown that the specific flu strain used in this study has undergone previous testing. At a certain dose, 78% of participants developed flu symptoms, a typical outcome in this type of study. Importantly, no serious side effects occurred, indicating the treatment's general safety. Participants experienced mild to moderate flu symptoms, which are normal and expected. This suggests the treatment is safe for healthy adults. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores the optimal infection dose and safety of a recombinant H3N2 influenza strain, specifically the A/Texas/71/2017 (H3N2, Clade 3C3a) strain. This study is different from typical flu treatments, which often involve antiviral medications like oseltamivir or zanamivir. Instead of treating the flu after infection, this trial seeks to understand how varying doses of the virus itself can safely induce an immune response. By pinpointing the optimal dose, researchers hope to enhance future vaccine development and improve preventive strategies against influenza.

What evidence suggests that this trial's treatments could be effective?

Research has shown that the A/Texas/71/2017 (H3N2) flu strain was used in studies where about 78% of participants developed flu symptoms after exposure to a specific amount. In this trial, researchers will assign participants to different cohorts to receive varying doses of this strain to evaluate its effects. This strain is notable for its ability to evade some of the body's natural defenses, known as antibodies, which typically fight infections. This characteristic makes it valuable for testing the efficacy of new vaccines or treatments. The aim is to identify a dose that safely induces symptoms in most participants, aiding in the development of future vaccines. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

Inclusion Criteria

Provide written informed consent prior to initiation of any study procedure

Are able to understand and comply with planned study procedures and be available for all study visits

Agree to remain an inpatient for at least 7 days after challenge AND until they have no viral shedding*, determined by qualitative Reverse Transcription - Polymerase Chain Reaction (RT-PCR) beginning on Study Day 6

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Challenge

Participants are challenged with a recombinant H3N2 influenza virus to determine the optimal infection dose and safety

1 day

1 visit (in-person)

Post-challenge Monitoring

Participants are monitored for viral shedding, clinical symptoms, and immune responses

8-10 days

Daily monitoring (inpatient)

Follow-up

Participants are monitored for safety and effectiveness after the challenge

57 days

What Are the Treatments Tested in This Trial?

Interventions

• Influenza RG-A/Texas/71/2017 (H3N2) Challenge
• Placebo

How Is the Trial Designed?

Group I: Cohort 3B Experimental Treatment 2 Interventions

10\^6 TCID50 of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5 mL per nostril) influenza virus (n=17) and Sham Sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5 mL per nostril) (n=1) administered intranasally on Day 1. N = 18

Group II: Cohort 3A Experimental Treatment 2 Interventions

10\^6 TCID50 of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5 mL per nostril) influenza virus (n=17) and Sham Sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5 mL per nostril) (n=1) administered intranasally on Day 1. If no safety threshold is met (halting conditions) proceed to Cohort 3B. N = 18

Group III: Cohort 2C Experimental Treatment 2 Interventions

10\^5 TCID50 of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5 mL per nostril) influenza virus (n=12) and Sham Sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5 mL per nostril) (n=1) administered intranasally on Day 1. If 70% or more of the subjects in Cohorts 2A, 2B, and 2C combined meet the case definition for influenza then the optimal dose of 10\^4 TCID50 will be selected. Cumulatively, if fewer than 70% of subjects in Cohorts 2A, 2B, and 2C meet the case definition for influenza the dose will escalate to include Cohort 3A. N = 13

Group IV: Cohort 2B Experimental Treatment 2 Interventions

10\^5 TCID50 of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5 mL per nostril) influenza virus (n=12) and Sham Sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5 mL per nostril) (n=1) administered intranasally on Day 1.If 70% or more subjects in Cohort 2A and 2B meet the case definition for influenza, proceed to Cohort 2C. Cumulatively, if fewer than 70% of subjects in Cohorts 2A and 2B meet the case definition for influenza, the dose will escalate to include Cohort 3A N = 13

Group V: Cohort 2A Experimental Treatment 2 Interventions

10\^5 TCID50 of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5 mL per nostril) influenza virus (n=12) and Sham Sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5 mL per nostril) (n=1) administered intranasally on Day 1. If 70% or more subjects in Cohort 2A meet the case definition for influenza, proceed to Cohort 1B. If fewer than 70% of subjects meet the case definition for influenza in Cohort 2A, the dose will escalate to include Cohort 3A. N = 13

Group VI: Cohort 1C Experimental Treatment 2 Interventions

10\^4 TCID50 of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5 mL per nostril) influenza virus (n=12) and sham sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5 mL per nostril) (n=1) administered intranasally on Day 1. If 80% or more of the subjects in Cohorts 1A, 1B, and 1C combined meet the case definition for influenza then the optimal dose of 104 TCID50 will be selected. Cumulatively, if fewer than 80% of subjects in Cohorts 1A, 1B, and 1C meet the case definition for influenza the dose will escalate to include Cohort 2A. N = 13

Group VII: Cohort 1B Experimental Treatment 2 Interventions

10\^4 TCID50 of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5 mL per nostril) influenza virus (n=12) and Sham Sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5 mL per nostril) (n=1) administered intranasally on Day 1. If 80% or more subjects in Cohort 1A and 1B meet the case definition for influenza, proceed to Cohort 1C. Cumulatively, if fewer than 80% of subjects in Cohorts 1A and 1B meet the case definition for influenza, the dose will escalate to include Cohort 2A. N = 13

Group VIII: Cohort 1A Experimental Treatment 2 Interventions

10\^4 TCID50of recombinant H3N2 (A/Texas/71/2017, clade 3C3a) 1.0 mL (0.5mL per nostril) influenza virus (n=12) and Sham Sucrose phosphate glutamate (SPG) inoculum 1.0 mL (0.5mL per nostril) (n=1) administered intranasally on Day 1. If 80% or more subjects in Cohort 1A meet the case definition for influenza, proceed to Cohort 1B. If fewer than 80% of subjects meet the case definition for influenza in Cohort 1A, the dose will escalate to include Cohort 2A. N = 13

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

In a study monitoring approximately 3.6 million doses of inactivated influenza vaccine (IIV) and 250,000 doses of live attenuated influenza vaccine (LAIV), no increased risk of adverse events such as seizures, Guillain-Barré syndrome, encephalitis, or anaphylaxis was found following vaccination.

The surveillance indicated that the 2012-2013 influenza vaccines were safe, as no elevated risks were identified compared to historical controls or self-matched intervals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Absence of associations between influenza vaccines and increased risks of seizures, Guillain-Barré syndrome, encephalitis, or anaphylaxis in the 2012-2013 season. Kawai, AT., Li, L., Kulldorff, M., 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 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]

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. 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 ...

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

H3N2 influenza hemagglutination inhibition method ... Here, we report on the qualification of an HAI assay for two representative H3N2 influenza strains, A/Texas/71/2017 and A/Singapore/INFIMH-16- ...

4. 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... The primary objective of these challenge studies is to assess and evaluate the effectiveness of various drug candidates and vaccines against these influenza ...

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 goal of this study is to find a challenge virus dose that is safe and can achieve a symptomatic influenza Attack Rate (AR) that will be ...

7. trial.medpath.com trial.medpath.com/clinical-trial/f359bc4dd146bfae/nct07063849-pre-existing-immunity-influenza-h3n2-challenge

Pilot Influenza Challenge Study | MedPath This is a research study to understand what happens when a person is infected with influenza ("flu") and how the body controls the infection.