Influenza Infection Clinical Trial
Official title:
Dose-Escalation Study of a Low Pathogenicity Avian H10N7 Influenza Virus in a Healthy Human Challenge Model
Background: Influenza, also called flu, is a virus. It can cause mild symptoms such as fever, cough, sore throat, and aches. Sometimes, flu can cause serious complications. Researchers want to see how people s immune systems respond to the flu. Objective: To find the smallest dose of influenza H10N7 virus that may cause an uncomplicated mild to moderate flu infection in healthy people. This dose will be used in the future to test how well new flu vaccines work. Eligibility: Healthy adults age 18-50. Design: Participants will be screened with: Physical exam with vital signs and weight Medical and medicine review Blood and urine tests Electrocardiogram to measure the heart s electrical activity. Screening tests will be repeated during the study. Participants will be tested for SARS-CoV-2 and other respiratory infections. For this, a swab will be inserted into the back of the nose. Participants will be admitted to an isolation room in the Clinical Center. They will stay in the hospital for at least 10 days. They will not have visitors. Participants may have a heart ultrasound. They may have lung function tests. For this, they will blow into a tube to measure lung capacity. One dose of the flu virus will be sprayed into participants nostrils. Participants will be monitored 24 hours a day. They will give nasal samples (using nasal washes and brushes) and blood samples almost every day. They will complete surveys about their symptoms. Participants will be discharged after they have 2 consecutive negative tests for flu. Participants will have at least 4 follow-up visits: 1 visit every 2 weeks for 8 weeks.
Study Description: This is a dose-finding and pathogenicity study following human challenge with a low pathogenicity avian influenza A H10N7. Participants will be inoculated with 1 dose of challenge virus during the study and then followed for a minimum of 9 weeks after inoculation. Progressively increasing doses will be used according to a specific plan until either the maximum dose is reached or at least 60% of participants develop mild to moderate influenza disease (MMID). Objectives: Primary Objective: 1. Determine the safe dose of A/Mallard/Ohio/99/1989 H10N7 human challenge virus that induces MMID in at least 60% of healthy volunteers or identify the rate of MMID at the maximum dose of 10^7 50% Tissue Culture Infective Dose (TCID50). Secondary Objective: 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. Exploratory Objective: 1. Discover viral factors necessary for human infection/adaptation and evaluate host immune response, viral replication, viral fitness, and intrahost evolution. 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: 1. Daily and total score on FLU-PRO questionnaire in each participant 2. Number and duration of symptoms and signs elicited by daily oral history and clinical exam 3. Duration and quantity of shedding of influenza in nasal wash/SAM by quantitative real-time polymerase chain reaction (rtPCR). Exploratory Endpoints: 1. Levels and type of influenza infection induced gene expression determined by human gene expression analysis and high-throughput sequencing. 2. Levels of mucosal and systemic antibodies after inoculation. 3. Change in viral genotype from the inoculum of virus isolated from infected participants. ;
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