Pilot Influenza Challenge Study

NCT07063849 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: SLU-25-001
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This is a research study to understand what happens when a person is infected with influenza ("flu") and how the body controls the infection. Healthy participants (challenge) will be infected with a strain of flu (H3N2), and followed to see what symptoms occur and when they occur. Blood will be drawn and nasopharyngeal (NP) swabs will be collected before participants are infected to understand if having antibodies can protect participants from flu infection or lead to a milder flu illness. Blood will also be drawn and NP swabs collected after participants are infected to understand how and when the body's immune response to flu occurs. Participants will also breathe through a device for virus collection every other day. Participants will be screened during one or more visits and will stay in the inpatient challenge unit for at least 10 days, maybe longer. Participants will complete a FLU PRO Diary Card daily. Blood will be drawn before the challenge and on Days 2, 4, and 8 while in the inpatient unit. NP samples will be taken every day to check for viruses and on certain days, immune responses such as antibodies. If on Day 8 (7 days after the challenge) the participant still has flu virus, medicine will be offered to treat the flu and the participant will be asked to stay in the challenge unit until NP swabs are negative for 2 consecutive days. Once the participant is discharged from the challenge unit, they will be asked to return to the clinic for 3 more visits. At the end of the study will be a final phone call.

Conditions

Influenza

Keywords

CHIM; Challenge

Outcome Measures

Primary Outcomes (9)

• Frequency of Adverse Events (AEs) and Serious Adverse Events (SAE) during inpatient challenge

  Post-challenge Day 1 through Day 8

• Frequency of AE and SAE post-inpatient discharge

  Thoughout the duration of the study (approximately three months post challenge)

• FLU-PRO symptomatic scoring of clinical symptoms twice daily

  Day 2 through at least Day 8 after challenge

• H3N2-specific polymerase chain reaction (PCR) on nasopharyngeal (NP) samples daily

  Day 2 through at least Day 8 post-challenge

• H3N2 viral loads as assessed by quantitative reverse transcription polymerase chain reaction (qRT-PCR).

  Days 2, 4, 6, and 8 post challenge

• H3N2 viral clonotypic complexity by Next-Gen sequencing of NP and exhaled breath samples.

  Days 2, 4, 6, and 8 post challenge

• Studies of biologically relevant mutations in the H3N2 viral genome post-challenge discovered by Next-Gen sequencing of NP and exhaled breath samples

  Days 2, 4, 6, and 8 post challenge

• Relative abundance of live H3N2 virus shed in exhaled breath within droplets (diameter greater than or equal to 5 microns) and aerosols (diameter less than 5 microns)

  Days 2, 4, 6, and 8 post challenge

• H3N2 viral loads as assessed by median tissue culture infective dose (TCID50) assays

  Days 2, 4, 6, and 8 post challenge

Secondary Outcomes (14)

• Proportions positive for virus shed into NP swabs on different days post-challenge using qRT-PCR.

  From baseline (Day -2 or -1) and daily from Day 2 through Day 8

• Baseline and post-challenge hemagglutination inhibition (HAI) and microneutralization (MN) antibody Geometric Mean Titers (GMTs) from serum

  Baseline (Day -2), and Days 8, 29, and 61.

• Percentage of participants achieving HAI and MN seroconversion (either a pre-challenge titer <1:10 and a post-challenge titer of greater than or equal to 1:40 or a pre-challenge titer of greater than or equal to 1:10 and a four-fold rise post-challenge

  Baseline (Day -2), and on Days 8, 29, and 61

• Baseline and post challenge H3HA-specific secretory GMTs by ELISA in NP swab samples

  Baseline (Day -2), and on Days 8, 29, and 61

• Spearman correlations between HAI/MN titers pre-challenge and FLU PRO scoring levels post-challenge

  Day 1 prior to the challenge through Day 14

Other Outcomes (12)

• Baseline and post-challenge neuraminidase inhibition (NAI) antibody GMTs from serum

  Baseline (Day -2), and on Days 8, 29, and 61.

• Percentage achieving NAI seroconversion (defined as either a pre-challenge titer of <1:10 and post challenge titer greater than or equal to 1:40 or a pre-challenge titer greater than or equal to 1:10 and a four fold rise in post-challenge antibody titer

  Baseline (Day -2), and on Days 8, 29, and 61.

• Spearman correlations between baseline A/Bethesda/MM2/H2N1 NAI antibody GMT and post challenge total AUC of NP viral shedding measured by qRT-PCR

  Baseline (Day -2) and on Days 2-8, 15, 29, and 61

Study Arms (1)

Single Arm

EXPERIMENTAL

One dose of RG-A/Texas/71/2017 Influenza Virus

Biological: A/Texas

Interventions

A/Texas BIOLOGICAL

Live Influenza Virus RG-A/Texas/71/2017 H3N2 Dose: 1.0 mL (0.5mL per nostril) of approximately 1x10\^6 TCID50 Administered intranasally by atomizer device Challenge virus will be administered once on Day 1

Single Arm

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Provide written informed consent prior to initiation of any study procedure.
• Are able to understand and comply with planned study procedures and be available for all study visits.
• Agree to remain an inpatient for at least seven days after challenge, AND until they have no virus shedding,1 determined by qualitative RT-PCR for a minimum of two consecutive days post-challenge 1For a minimum of seven days post-challenge (Study Day 8).
• Healthy2 males and non-pregnant, non-breastfeeding females3 aged ≥18 and ≤45 years of age, inclusive, at enrollment.
• \. Women of childbearing potential4 must agree to use or have practiced true abstinence5 or use at least 1 acceptable primary form of contraception6,7 These criteria are applicable to females in a heterosexual relationship and child-bearing potential (i.e., the criteria do not apply to participants in a same sex relationship).
• Not of child- bearing potential - post-menopausal females (defined as having a history of amenorrhea for at least one year) or a documented status as being surgically sterile (hysterectomy, bilateral oophorectomy, tubal ligation/salpingectomy, or Essure® placement with history of documented radiological confirmation test at least 90 days after the procedure).
• True abstinence is 100% of time no sexual intercourse (male's penis enters the female's vagina). (Periodic abstinence \[e.g. calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception).
• Acceptable forms of primary contraception include intrauterine devices, birth control pills, and injectable/implantable/insertable hormonal birth control products monogamous relationship with a vasectomized partner who has been vasectomized for180 days or more prior to the subject receiving the influenza challenge virus.
• Must use at least one acceptable primary form of contraception for at least 30 days prior to admission and at least one acceptable primary form of contraception during the remainder of the study.
• \. Non-habitual smoker8 of tobacco, or marijuana. 8Non-habitual smokers are those who smoke no more than four cigarettes, other tobacco products, vaping (e-cigarettes) or marijuana in a week for more than three months and agree not to smoke cigarettes, other tobacco products, e-cigarettes and/or marijuana products during participation in the study.
• \. No self-reported or known history of alcoholism or drug use within the last 30 days and agrees to abstain from alcohol and drugs9 for at least one week before admission and throughout the inpatient period.
• including forms of marijuana not included in criterion 6 8. Negative drug urine toxicology result on screening (i.e., amphetamines, cocaine, and opiates). and on admission to the challenge unit (i.e., amphetamines, cocaine, and opiates).
• \. Agree not to use the listed10 prescription or over-the-counter medications within 7 days prior to inpatient stay and through inpatient stay, unless approved by the investigator.
• Oseltamivir, zanamivir, peramivir, baloxavir marboxil, amantadine (generic) and rimantadine (Flumadine and generic), aspirin, intranasal steroids, decongestants, antihistamines, and other non-steroidal anti-inflammatory drugs (NSAIDs).

You may not qualify if:

• \. Does not have an ongoing symptomatic condition12 for which subject has had or has ongoing medical investigations but has not yet received a diagnosis or treatment plan.
• e.g., ongoing fatigue without a diagnosis for symptom. 12. Vital signs as follows13: 13pulse is 47 to 99 beats per minute, inclusive; systolic blood pressure is 85 to 139 mmHg, inclusive; diastolic blood pressure is 55 to 89 mmHg, inclusive; SpO2 \>95%; RR\<18; oral temperature is less than 100.0°F.
• \. Eligibility laboratory values (WBC, Absolute Lymphocyte Count, Hgb, PLTs, ALT and Cr) are within acceptable parameters.
• \. Body mass index (BMI) \>18.5 and \<35 kg/m2 at screening. 15. Other screening tests (ECG and CXR) are within normal reference range or not deemed clinically significant by the PI or appropriate sub-investigator14 14Designated clinician licensed to make medical diagnoses and listed on the Form FDA 1572 16. H3N2 Challenge virus MN titer done in SLU VTEU research lab during screening to allow selection for enrollment of subjects with the broadest range of pre-existing H3N2 immunity.
• \. Negative test for HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) at screening blood draw.
• \. Negative respiratory virus panel by BIOFIRE® FILMARRAY® respiratory panel by bioMérieux or by Luminex xTAG® on Day -2, and Day -1.
• Female subject who has a positive pregnancy test on screening or admission, is breastfeeding or planning to become pregnant from 30 days prior to challenge through the end of the study.
• Presence of self-reported or medically documented significant medical or psychiatric condition(s)15 15Significant medical or psychiatric conditions include but are not limited to:
• Respiratory disease (e.g., chronic obstructive pulmonary disease \[COPD\], asthma) requiring daily medications15 currently or any treatment of respiratory disease exacerbations (e.g., asthma exacerbation) in the last 5 years 16Asthma medications: inhaled, oral, or intravenous (IV) corticosteroids, leukotriene modifiers, long and short acting beta agonists, theophylline, ipratropium, biologics.
• Presence of any febrile illness or symptoms suggestive of a respiratory infection within two weeks prior to CHI.
• Cardiovascular disease (e.g., congestive heart failure, cardiomyopathy, ischemic heart disease) or history of myocarditis or pericarditis as an adult.
• Neurological or neurodevelopmental conditions (e.g., epilepsy, stroke, seizures, encephalopathy, focal neurologic deficits, Guillain-Barre syndrome, encephalomyelitis or transverse myelitis).
• Ongoing malignancy or recent diagnosis of malignancy in the last five years excluding basal cell carcinoma of the skin, which is allowed.
• An autoimmune disease.
• An immunodeficiency of any cause.

Sponsors & Collaborators

• Daniel Hoft, MD, PhD: lead

Study Sites (1)

Saint Louis University Center for Vaccine Development

St Louis, Missouri, 63104, United States

Location

Related Publications (22)

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MeSH Terms

Conditions

Influenza, Human

Condition Hierarchy (Ancestors)

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

Study Officials

• Daniel F. Hoft, MD, PhD

  Saint Louis University Center for Vaccine Development

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Internal Medicine

Study Record Dates

• First Submitted: June 16, 2025
• First Posted: July 14, 2025
• Study Start: May 20, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: July 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)