Low Pathogenicity Avian H10N7 Influenza Virus in a Healthy Human Challenge Model

NCT05436444 | Completed Phase 1 FDA Drug

• 2 other identifiers: 20016020-I-0160
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Influenza Infection

Keywords

Influenza A; H10N7; Challenge Model; Influenza; Human Challenge

Outcome Measures

Primary Outcomes (1)

• The rate of MMID, defined as a positive FDA-approved clinical test for influenza plus one or more influenza symptoms, is induced.

  To determine the dose of A /Mallard/Ohio-99/MM4/1989 H10N7 human challenge virus that induces MMID in at least 60% of healthy volunteers.

  9 days

Secondary Outcomes (1)

• Daily and total score on FLUPRO questionnaire and number and duration of symptoms and signs elicited by daily oral history and clinical exam

  28 days

Study Arms (1)

1

EXPERIMENTAL

All participants receive challenge virus

Biological: A/Mallard/Ohio-99/MM4/1989 H10N7

Interventions

A/Mallard/Ohio-99/MM4/1989 H10N7 BIOLOGICAL

The human challenge virus will be administered intranasally to each participant using a nasal atomizer. A total volume of up to 2 mL will be administered split between both nostrils of each participant.

1

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• An individual must meet all of the following criteria to be eligible for study participation:
• Greater than or equal to 18 and less than or equal to 50 years of age.
• Able to provide consent.
• Agrees to not use tobacco products, marijuana, or vaping products during participation in this study.
• Willing to remain in isolation for a minimum of 10 calendar days (or for the duration of viral shedding) and to comply with all study requirements.
• A male subject is eligible for the study if he meets one of the following criteria, beginning at least 4 weeks prior to enrollment and continuing until 10 weeks after administration of the human challenge virus and follow-up visit #4:
• Is infertile, including history of successful vasectomy.
• Agrees to practice abstinence.
• A female participant is eligible for this study if she is not pregnant or breastfeeding and meets one of the following criteria, beginning at least 4 weeks prior to enrollment and continuing until 10 weeks after administration of the human challenge virus and follow-up visit #4:
• Is infertile, including postmenopausal status (as defined by no menses for greater than or equal to 1 year) or history of hysterectomy.
• Agrees to practice abstinence.
• Agrees that, with heterosexual intercourse with a fertile male partner, she will use an acceptable form of contraception and her male partner will use a condom with spermicide. Acceptable effective methods of female contraception include the following: bilateral tubal ligation, implant of levonorgestrel, injectable progestogen, intrauterine device, oral contraceptive pills, and diaphragm with spermicide.
• Willing to have samples stored for future research.
• Human immunodeficiency virus (HIV) uninfected with a negative test within 60 days of inoculation (Day 0).

You may not qualify if:

• An individual meeting any of the following criteria will be excluded from study participation:
• Has self-reported or medically documented significant medical condition including but not limited to:
• Chronic pulmonary disease (e.g., asthma, emphysema).
• Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, cardiac surgery, ischemic heart disease, known anatomic defects).
• Chronic medical conditions requiring close medical follow-up or hospitalization during the past 5 years (e.g., insulin-dependent diabetes mellitus, renal dysfunction, hemoglobinopathies).
• Immunosuppression or ongoing malignancy.
• Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, stroke, seizures).
• Post-infectious or post-vaccine neurological sequelae.
• Has close or household (i.e., share the same apartment or house) high-risk contacts including but not limited to:
• Persons greater than or equal to 65 years of age.
• Children less than or equal to 5 years of age.
• Residents of nursing homes.
• Persons of any age with significant chronic medical conditions such as:
• Chronic pulmonary disease (e.g., asthma).
• Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, cardiac surgery, ischemic heart disease, known anatomic defects).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Beare AS, Webster RG. Replication of avian influenza viruses in humans. Arch Virol. 1991;119(1-2):37-42. doi: 10.1007/BF01314321.

  PMID: 1863223 BACKGROUND

• Memoli MJ, Czajkowski L, Reed S, Athota R, Bristol T, Proudfoot K, Fargis S, Stein M, Dunfee RL, Shaw PA, Davey RT, Taubenberger JK. Validation of the wild-type influenza A human challenge model H1N1pdMIST: an A(H1N1)pdm09 dose-finding investigational new drug study. Clin Infect Dis. 2015 Mar 1;60(5):693-702. doi: 10.1093/cid/ciu924. Epub 2014 Nov 20.

  PMID: 25416753 BACKGROUND

• KASEL JA, ALFORD RH, KNIGHT V, WADDELL GH, SIGEL MM. EXPERIMENTAL INFECTION OF HUMAN VOLUNTEERS WITH EQUINE INFLUENZA VIRUS. Nature. 1965 Apr 3;206:41-3. doi: 10.1038/206041a0. No abstract available.

  PMID: 14334358 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Study Officials

• Matthew J Memoli, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 17, 2022
• First Posted: June 29, 2022
• Study Start: October 23, 2023
• Primary Completion: December 17, 2024
• Study Completion: December 17, 2024
• Last Updated: March 11, 2025

Record last verified: 2025-02-20

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)