NCT07215871

Rechallenge With a Low Pathogenicity Avian H10N7 Influenza Virus in Healthy Human Volunteers Previously Challenged With H10N7 Influenza

• Status: Enrolling By Invitation
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 33 (estimated)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

Background: Influenza (flu) is a virus that can infect humans and animals. In humans, the flu can cause mild symptoms such as fever, cough, sore throat, runny nose, muscle aches, headaches, and fatigue. It can also cause sinus infections or pneumonia. Some flu strains, such as H5N1 and H7N9, which come from birds, can lead to more severe symptoms or death. Others, like H10N7, also come from birds but usually cause mild symptoms. Researchers want to study bird flu in humans to help develop new flu vaccines and treatments. Objective: To learn more about how bird flu viruses infect humans. Eligibility: Healthy people aged 18 to 55 years who were infected with the H10N7 bird flu strain as part of a previous study. Design: Participants who were infected with H10N7 in a previous study will be infected again with the same virus. The virus will be sprayed into their nostrils. Participants will stay in the hospital for at least 9 days. They will stay in an isolation unit. No outside visitors will be allowed. During their stay, participants will provide blood, urine, and nasal fluid samples. They will have tests of their heart and lung function. They will complete questionnaires about their symptoms. Participants will remain in the hospital until they test negative for the flu 2 days in a row. They will continue to complete questionnaires about their symptoms for 2 weeks after they were infected with the virus. Participants will have 2 follow-up visits, at 5 weeks and 9 weeks after they were infected. They will have a physical exam and provide samples of blood and nasal fluids. They will have a test of their heart function.

Detailed description

This is a single-center study to evaluate infection after a second exposure to a low pathogenicity avian influenza A H10N7. Participants who have previously been challenged with H10N7 willbe rechallenged with 10\^7 Tissue Culture Infective Dose (TCID50) virus and followed for a minimum of 9 weeks after inoculation. 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-exposure despite the potential development of immunity after the last challenge. This will be evaluated by monitoring participants for influenza disease symptoms, viral shedding, and immunological response. The primary way MMID will be determined will be through clinical testing for influenza and symptom monitoring. Objectives: Primary Objective: 1\. Determine if participants develop MMID after a second challenge with A/Mallard/Ohio/99/1989 H10N7. Secondary Objectives: 1. Evaluate clinical disease, identify clinical markers, and observe initiation of shedding, length of shedding, and pathogenesis in participants with low pathogenicity avian influenza A infection. 2. Evaluate immune response after a second challenge with H10N7 compared to the initial challenge. Exploratory Objectives: 1. Evaluate additional host immune responses, viral replication, viral fitness, and intrahost evolution. 2. Evaluate clinical and virologic outcomes as outlined in primary and secondary objectives in subgroups of interest. 3. Determine correlates of protection against H10N7 challenge. Endpoints: Primary Endpoint: 1. Rate of MMID, defined as a positive US Food and Drug Administration (FDA)-approved clinical test for influenza plus one or more influenza symptoms. Secondary Endpoints: 2. Clinical outcomes after challenge including: a. Mean duration and quantity of shedding of influenza in nasal wash/synthetic absorptive matrices (SAM) by quantitative real-time polymerase chain reaction (PCR). b. Mean duration and number of symptoms and signs elicited by daily oral history and clinical exam compared to prior infection. c. Mean daily and total score of influenza patientreported outcome (FLU-PRO) questionnaire. 3. Immunological responses after challenge including: 1. Serum hemagglutination (HA) inhibition (HAI) and/or enzyme-linked immunosorbent assay (ELISA) against HA. 2. Serum neuraminidase (NA) inhibition (NAI) and/or ELISA titers against NA. 3. Mucosal ELISA titers against HA and NA. Exploratory Endpoints: 1. Immune response and viral factors including: 1. Levels and type of influenza infection induced gene expression determined by human gene expression analysis and high-throughput sequencing. 2. Characterization of B- and T-cell responses. 3. Change in viral genotype from the inoculum of virus isolated from infected participants. 2. MMID, shedding, symptom rates, and immune responses in subgroups of interest (including but not limited to those who had/had not MMID after the first challenge, had/had not shedding after first challenge). 3. Immunological correlates of protection (like HAI, NAI, mucosal responses, cellular responses) in protecting against clinical outcomes (including MMID, shedding, symptoms).

Conditions

• Influenza Infection
• Infections
• Respiratory Virus Infections
• Respiratory Tract Infections
• RNA Viruses
• Orthomyxoviridae Infections
• Viral Diseases

Interventions

Type	Name	Description
BIOLOGICAL	A/Mallard/Ohio-99/MM4/1989 H10N7	Low pathogenicity avian influenza virus H10N7

Timeline

• Start date: 2026-04-22
• Primary completion: 2026-09-29
• Completion: 2027-09-29
• First posted: 2025-10-14
• Last updated: 2026-04-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study