Examining immune responses to the flu virus

Influenza Human Challenge Model

This study tests how the immune system responds to the H3N2 flu virus in healthy people to help improve future flu vaccines and treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years to 49 Years
• Sex: All
• Sponsor: Emory University (Academic / other)
• Drugs / interventions: prednisone
• Locations: 2 sites (Atlanta, Georgia and 1 other locations)
• Trial ID: NCT05332899 on ClinicalTrials.gov

What this trial studies

This study investigates how the immune system reacts to the H3N2 influenza virus during and after infection, as well as how the virus spreads in the environment. It utilizes a specifically produced H3N2 influenza challenge virus in a controlled setting to assess safety and immune responses in healthy participants. The study aims to gather data that could inform future influenza vaccinations and therapeutics, addressing the limitations of current vaccines and antiviral treatments.

Who should consider this trial

Good fit: Ideal candidates are healthy males and non-pregnant, non-breastfeeding females aged 18 to 49 years.

Not a fit: Patients with chronic pulmonary or cardiovascular diseases, or those who are pregnant or breastfeeding, may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved influenza vaccines and treatments, enhancing patient outcomes during flu seasons.

How similar studies have performed: Other studies using influenza challenge models have shown success in understanding immune responses, making this approach both relevant and promising.

Eligibility criteria

Inclusion Criteria:

* Provide written informed consent prior to initiation of any study procedures.
* Are able to understand and comply with all planned study procedures.
* Healthy males and non-pregnant, non-breast-feeding females aged ≥18 and ≤49 years of age inclusive at enrollment.
* Women of childbearing potential must be practicing abstinence or using an acceptable method of birth control for at least 30 days prior to enrollment through the duration of the trial. Male subjects must agree not to father a child for the duration of the trial.
* Women of childbearing potential must have a negative serum or urine pregnancy test at screening and negative urine pregnancy test within 24 hours prior to challenge.
* Are in good general health, as determined by the study investigator within 30 days of challenge and do not have any of the following conditions:

  * Chronic pulmonary disease (e.g., asthma or reactive airway disease, 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., diabetes mellitus, renal dysfunction, hemoglobinopathies)
  * Immunosuppression or ongoing malignancy or history of malignancy (excluding nonmelanotic skin cancer in remission without treatment for more than 5 years)
  * Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, stroke, seizures)
  * History of postinfectious or postvaccine neurological sequelae
  * Autoimmune, inflammatory, vasculitic or rheumatic disease, including but not limited to systemic lupus erythematosus, polymyalgia rheumatica, rheumatoid arthritis or scleroderma
* Demonstrate knowledge and comprehension of the study by scoring ≥70% on a quiz of the study protocol and policies.
* Agrees to not use cigarettes, e-cigarettes, marijuana, or other tobacco products during the quarantine period.
* Agrees to not use prescription or over-the-counter medications that could impact influenza challenge efficacy or symptoms (including oseltamivir, zanamivir, peramivir, baloxavir marboxil, amantadine and rimantadine, aspirin, intranasal steroids, acetaminophen, decongestants, antihistamines, and other NSAIDs), within 14 days prior to quarantine and through the quarantine period, unless approved by the investigator.

Exclusion Criteria:

* Have household contact with or have daily contact with:

  * Children under 5 years of age
  * Children and/or teenagers who are receiving long-term aspirin therapy
  * Women who are pregnant or who are trying to become pregnant
  * Persons older than 65 years of age
  * Persons of any age with significant chronic medical conditions such as: chronic pulmonary disease, chronic cardiovascular disease, contacts who required medical follow-up or hospitalization during the past 5 years because of chronic metabolic disease, immunosuppression or cancer, neurological and neurodevelopmental conditions
* Are healthcare workers with patient contact in the 2 weeks after influenza challenge.
* Plan to be living in a confined environment (e.g. ship, camp, or dormitory) within 2 weeks after receiving the challenge strain.
* For females, are pregnant or plan to become pregnant at any time between the Screening Visit through the duration of the trial.
* Are breastfeeding or plan to breastfeed at any given time throughout the study.
* Have a body mass index (BMI) less than or equal to 18.5 and greater than or equal to 35.
* Smoke more than 4 cigarettes, e-cigarettes, marijuana, or other tobacco products on weekly basis within 60 days prior to challenge.
* Have moderate or severe illness and/or an oral temperature ≥100°F and/or diarrhea or vomiting within seven days prior to challenge.
* Have a pulse rate less than 55 beats per minute (bpm) or \>100 bpm. If heart rate is \<55 bpm and the investigator determines that this is not clinically significant (e.g., athletes) and heart rate increases \>55 bpm on moderate exercise (two flights of stairs), subject will not be excluded.
* Have a systolic blood pressure less than 90 mmHg or greater than 140 mmHg on two separate measurements (screening and pre-challenge).
* Have a diastolic blood pressure less than 50 mmHg or greater than 90 mmHg on two separate measurements (screening and pre-challenge).
* Have long-term (≥2 weeks) use of high-dose oral (≥20 mg per day prednisone or equivalent) or parenteral glucocorticoids, or high-dose inhaled steroids for greater than 7 days in the last 3 months.
* Have an active HIV, hepatitis B, or hepatitis C infection.
* Have screening laboratory test results (white blood cells (WBCs), absolute neutrophil count (ANC), hemoglobin (Hgb), platelets) that are outside the laboratory reported normal values and deemed clinically significant by the study investigator.
* Have a serum creatinine greater than 1.1 x upper limit of normal (ULN).
* Have an alanine aminotransferase (ALT) greater than 1.1 x ULN.
* Have abnormal findings on screening electrocardiogram deemed clinically significant by study investigator.
* Have abnormal findings on screening chest X-ray deemed clinically significant by study investigator.
* Have ongoing drug abuse/dependence (including alcohol), or a history of these issues within 5 years of enrollment.
* Have positive urine/serum test for drugs of abuse (i.e. cocaine, benzodiazepines, opiates, or metabolites). Positive results for tetrahydrocannabinol (THC) will not be considered exclusionary. Metabolites and amphetamines as prescribed for a documented medical condition will also not be considered exclusionary.
* Have any medical, psychiatric, occupational, or behavioral problems that could make it difficult for the subject to comply with the protocol as determined by the investigator.
* Have received experimental products within 30 days before study entry or plan to receive experimental products at any time during the study.
* Plans to enroll in another clinical trial that could interfere with safety assessment of the investigational product at any time during the study period, including study interventions such as drugs, biologics or devices.
* Plan to donate blood during the course of the study.
* Have received a live vaccine within 30 days before study entry or plan to receive a live vaccine prior to Day 31 of the challenge.
* Have received an inactivated vaccine within 14 days before study entry or plan to receive an inactivated vaccine prior to Day 14 of the challenge.
* Have received parenteral immunoglobulin or blood products within 3 months of the study start, or plan to receive parenteral immunoglobulin or blood products for the duration of the study.
* Have a known close contact with anyone known to have influenza in the past 7 days prior to screening or challenge.
* Have a known history of allergy to anti-influenza drugs, more than 2 classes of antibiotics or severe egg allergy.
* Have any condition that, in the judgment of the study investigator, is a contraindication to protocol participation or impairs the subject's ability to give informed consent.
* Have a BIOFIRE® FILMARRAY® respiratory panel that identifies any pathogen on the day of admission.
* Clinically significant abnormality as deemed by the study investigator on the PFT and/or spirometry at screening visit (if applicable, for inhalation challenge only.)

Where this trial is running

Atlanta, Georgia and 1 other locations

• Hope Clinic — Atlanta, Georgia, United States (Recruiting)
• Emory University Hospital — Atlanta, Georgia, United States (Recruiting)

Study contacts

• Principal investigator: Nadine Rouphael, MD — Emory University
• Study coordinator: Nadine Rouphael, MD

Conditions Influenza