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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05436444
Recruitment Status : Not yet recruiting
First Posted : June 29, 2022
Last Update Posted : September 30, 2022
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

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.


Condition or disease Intervention/treatment Phase
Influenza Infection Biological: A/Mallard/Ohio-99/MM4/1989 H10N7 Phase 1

Detailed Description:

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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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Dose-Escalation Study of a Low Pathogenicity Avian H10N7 Influenza Virus in a Healthy Human Challenge Model
Estimated Study Start Date : October 5, 2022
Estimated Primary Completion Date : May 31, 2024
Estimated Study Completion Date : May 31, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 1
All participants receive challenge virus
Biological: A/Mallard/Ohio-99/MM4/1989 H10N7
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.




Primary Outcome Measures :
  1. The rate of MMID, defined as a positive FDA-approved clinical test for influenza plus one or more influenza symptoms, is induced. [ Time Frame: 9 days ]
    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.


Secondary Outcome Measures :
  1. Daily and total score on FLUPRO questionnaire and number and duration of symptoms and signs elicited by daily oral history and clinical exam [ Time Frame: 28 days ]
    To evaluate clinical disease, identify clinical markers, and observe initiation of shedding, length of shedding, and pathogenesis in participants



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

An individual must meet all of the following criteria to be eligible for study participation:

  1. Greater than or equal to 18 and less than or equal to 50 years of age.
  2. Able to provide consent.
  3. Agrees to not use tobacco products, marijuana, or vaping products during participation in this study.
  4. 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.
  5. 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:

    1. Is infertile, including history of successful vasectomy.
    2. Agrees to practice abstinence.
    3. Agrees that, with heterosexual intercourse with a fertile female partner, he will use a condom with spermicide and his female partner (including those who have undergone bilateral tubal ligation) will use an acceptable form of contraception (see inclusion criterion 6c).
  6. 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:

    1. Is infertile, including postmenopausal status (as defined by no menses for greater than or equal to 1 year) or history of hysterectomy.
    2. Agrees to practice abstinence.
    3. 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.
  7. Willing to have samples stored for future research.
  8. Human immunodeficiency virus (HIV) uninfected with a negative test within 60 days of inoculation (Day 0).

EXCLUSION CRITERIA:

An individual meeting any of the following criteria will be excluded from study participation:

  1. Has self-reported or medically documented significant medical condition including but not limited to:

    1. Chronic pulmonary disease (e.g., asthma, emphysema).
    2. Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, cardiac surgery, ischemic heart disease, known anatomic defects).
    3. Chronic medical conditions requiring close medical follow-up or hospitalization during the past 5 years (e.g., insulin-dependent diabetes mellitus, renal dysfunction, hemoglobinopathies).
    4. Immunosuppression or ongoing malignancy.
    5. Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, stroke, seizures).
    6. Post-infectious or post-vaccine neurological sequelae.
  2. Has close or household (i.e., share the same apartment or house) high-risk contacts including but not limited to:

    1. Persons greater than or equal to 65 years of age.
    2. Children less than or equal to 5 years of age.
    3. Residents of nursing homes.
    4. 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).
      • Chronic medical conditions requiring medical follow-up or hospitalization during the past 5 years (e.g., insulin-dependent diabetes mellitus, renal dysfunction, hemoglobinopathies).
      • Immunosuppression or cancer.
      • Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, stroke, seizures).
      • Persons who are receiving long-term aspirin therapy.
      • Women who are pregnant, trying to become pregnant, or breastfeeding.
  3. Has a body mass index (BMI) less than or equal to 18.5 or greater than or equal to 35.
  4. Smokes more than 4 cigarettes or other tobacco products on a weekly basis or any type of vaping/e-cigarette use more than 4 times per week.
  5. History of facial reconstructive procedures or nasopharyngeal malformation.
  6. Positive for Hepatitis B or Hepatitis C infections.
  7. Complete blood count (CBC) with differential outside of the NIH Department of Laboratory Medicine (DLM) normal reference range and deemed clinically significant by the PI.
  8. Grade 2 or higher Hemoglobin for female participants or Grade 1 or higher Hemoglobin for male participants.
  9. Chemistries in the acute care, mineral, and/or hepatic panels, and/or any of the following: lactate dehydrogenase (LDH), uric acid, creatine kinase, and total protein outside of the NIH DLM normal reference range and deemed clinically significant by the PI.
  10. Urinalysis outside of the NIH DLM normal reference range and deemed clinically significant by the PI.
  11. Clinically significant abnormality as deemed by the PI on ECG.
  12. Clinically significant abnormality as deemed by the PI on ECHO.
  13. Clinically significant abnormality as deemed by the PI on the PFT and/or spirometry.
  14. Recent acute illness within 1 week of admission to the NIH CC.
  15. Known allergy to any component of the interventional agent.
  16. Known allergy to treatments for influenza (including but not limited to oseltamivir, nonsteroidals).
  17. Known allergy to 2 or more classes of antibiotics (e.g., penicillins, cephalosporins, fluoroquinolones, or glycopeptides).
  18. Receipt of influenza vaccine within 8 weeks prior to enrollment.
  19. Receipt of blood or blood products (including immunoglobulins) within 3 months prior to enrollment.
  20. Receipt of any unlicensed drug within 3 months or 5.5 half-lives (whichever is greater) prior to enrollment.
  21. Receipt of any unlicensed vaccine within 6 months prior to enrollment.
  22. Self-reported or known history of current alcoholism or drug abuse, or positive urine/serum test for drugs of abuse (i.e., amphetamines, cocaine, benzodiazepines, opiates, or metabolites, but not tetrahydrocannabinol or metabolites).
  23. Self-reported or known history of psychiatric or psychological issues deemed by the PI to be a contraindication to protocol participation
  24. Known close contact with anyone known to have influenza in the past 7 days.
  25. Known close contact with anyone known to have COVID-19 in the past 14 days.
  26. Diagnosed with COVID-19 in the 90 days prior to enrollment. The 90 days will be counted from the first positive test for SARS-CoV-2 or if a test was not done (i.e., presumptive positive), then the 90 days will be counted from the date of symptom onset.
  27. Diagnosed with COVID-19 and had complications, including, but not limited to: inpatient hospitalization, required the use of oxygen, and/or on-going sequelae.
  28. Non-English speaking participants.
  29. Any condition that, in the judgment of the PI, is a contraindication to protocol participation or impairs the volunteer s ability to give informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05436444


Contacts
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Contact: Rani S Athota, Ph.D. (301) 594-0803 kotar@mail.nih.gov
Contact: Matthew J Memoli, M.D. (301) 443-5971 mm982v@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Principal Investigator: Matthew J Memoli, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
Additional Information:
Publications:
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT05436444    
Other Study ID Numbers: 200160
20-I-0160
First Posted: June 29, 2022    Key Record Dates
Last Update Posted: September 30, 2022
Last Verified: June 16, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: .We are not working with any outside collaborators that require this information.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
Influenza A
H10N7
Challenge Model
Influenza
Human Challenge
Additional relevant MeSH terms:
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Influenza, Human
Respiratory Tract Infections
Infections
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Diseases