Establishing a Controlled Human Infection Model for Influenza H3N2 as a Foundation for Pandemic Preparedness

NCT07305207 | Not Yet Recruiting Phase 1 DMC

• 2 other identifiers: CI2403OCT-104219
• Study Type: interventional
• Target: 32
• Locations: 0 countries
• Sites: N/A

Brief Summary

The overall objective is to establish an influenza Controlled Human Infection Model (CHIM) in Canada that can be used to assess the safety and efficacy of candidate vaccines, biologics, and therapeutics targeting influenza viruses.

Conditions

Influenza (Healthy Volunteers)

Keywords

human challenge; Controlled human infection model; Influenza; intranasal challenge; Phase 1 clinical trial; Immune response

Outcome Measures

Primary Outcomes (1)

• Symptomatic influenza-virus infection

  Viral shedding (as determined by a detectable quantitative RT-qPCR result on at least two days and/or at least one positive culture) beginning 24 hours after challenge (Study Day 2) until Study Day 8 and A cumulative symptom score of ≥6 from daily component symptoms computed across any consecutive 5-day window starting on Study Day 2 up to Study Day 8 post-challenge using a Modified Jackson Score (MJS).

  Study Day 2 until Study Day 8

Secondary Outcomes (8)

• Compare rates of Symptomatic influenza-virus infection across doses administered.

  Study Day 1 up to Study Day 29

• Establish the safety profile of a live recombinant influenza strain RG-A/Texas/71/2017 (H3N2, Clade 3C3a) following challenge in healthy adult volunteers.

  Study Day 1 up to Study Day 85

• Assess the viral shedding

  Study Day 1 up to Study Day 85

• Assess the peak viral load

  Study Day 1 up to Study Day 85

• Measure the duration of the viral shedding

  Study Day 1 up to Study Day 85

Other Outcomes (12)

• Determine optimal collection time points for biological specimens to assess mucosal and systemic cellular responses to influenza infection (in nasopharyngeal swabs (NPSs), nasal washes (NWs), serum, saliva secretions, peripheral blood) post-challenge.

  Study Day 1 up to Study Day 85

• Compare detection of virus by culture and by RT-qPCR.

  Study Day 1 up to Study Day 8

• Evaluate effects of age, sex, gender, ethnicity, baseline antibody titers, and prior receipt of seasonal influenza vaccine on SII.

  Study Day 1 up to Study Day 85

Study Arms (3)

Experimental: Group 1: Dose Number 1 (10^5)

EXPERIMENTAL

Participants will be inoculated intranasally with a single dose of the A/H3N2 challenge virus or placebo

Biological: Intranasal inoculation of RG-A/Texas/71/2017 (H3N2) influenza in each naris on Day 1 of the study.

Experimental: Group 1: Dose Number 2 (10^4)

EXPERIMENTAL

Participants will be inoculated intranasally with a single dose of the A/H3N2 challenge virus or placebo

Biological: Intranasal inoculation of RG-A/Texas/71/2017 (H3N2) influenza in each naris on Day 1 of the study.

Experimental: Group 1: Dose Number 3 (10^6)

EXPERIMENTAL

Participants will be inoculated intranasally with a single dose of the A/H3N2 challenge virus or placebo

Biological: Intranasal inoculation of RG-A/Texas/71/2017 (H3N2) influenza in each naris on Day 1 of the study.

Interventions

Intranasal inoculation of RG-A/Texas/71/2017 (H3N2) influenza in each naris on Day 1 of the study. BIOLOGICAL

Participants will be inoculated intranasally with a single dose of the A/H3N2 challenge virus or placebo

Experimental: Group 1: Dose Number 1 (10^5); Experimental: Group 1: Dose Number 2 (10^4); Experimental: Group 1: Dose Number 3 (10^6)

Eligibility Criteria

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

You may qualify if:

• Written informed consent obtained from the participant.
• years of age.
• Good general health status, as determined by history and physical examination conducted no longer than 30 days prior to the challenge date.
• HAI antibody titer ≤1:40 against influenza A/Texas/71/2017 (H3N2).
• Eligibility laboratory values\* (complete blood cell count with differential (CBC-D), biochemistry (creatinine (Cr), total bilirubin, blood urea nitrogen (BUN), aspartame aminotransferase (AST), alanine transaminase (ALT), and c-reactive protein (CRP))\*Labs within normal range or grade 1 abnormalities deemed not clinically significant by a study investigator are considered acceptable.
• Vital signs\*\* as follows:
• Pulse is 47 to 99 beats per minute
• Systolic blood pressure is 85 to 139 mmHg
• Diastolic blood pressure is 55 to 89 mmHg
• SpO2 ≥ 95%; RR ≤ 18
• Oral temperature is less than 38.1°C \*\*Clinical judgement when characterizing vital signs will be used in the context of certain populations according to the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (e.g. conditioned athletes, white coat hypertension etc.)
• If a person is at risk of becoming pregnant, has practiced adequate contraception for 28 days prior to challenge, and has a negative pregnancy test on the screening day and the day before influenza A/H3N2 challenge (Check-in Day) and has agreed to continue adequate contraception until 60 days after challenge.
• Risk of pregnancy is defined as any individual assigned female at birth or with reproductive capacity who is sexually active with individuals with sperm-producing capabilities. Individuals who have received the following are considered to not have reproductive capacity:
• Documented hysterectomy
• Documented bilateral salpingectomy

You may not qualify if:

• Underlying chronic medical condition requiring ongoing follow-up and monitoring by a physician (e.g., diabetes, seizure disorder).
• Underlying renal disease or disorders requiring ongoing follow-up and monitoring by a physician. In the event a participant has a minimally elevated BUN and/or Cr at screening, the participant will either be excluded or an eCRF or creatinine clearance may be conducted to determine eligibility.
• Underlying coagulation disorder history. In the event a participant reports a personal history of undiagnosed prolonged bleeding and/or recurrent nosebleeds or a personal or family history of coagulation disorders, a bleeding panel (PTT, INR, fibrinogen) will be used to rule out coagulopathy.
• Underlying cardiac conditions including:
• Hypertension, angina, or prior myocardial infarction
• Structural or functional cardiac disease (e.g., dilated cardiomyopathy, congestive heart failure)
• With a history of arrhythmias/dysrhythmias (e.g., torsades de pointes, atrial fibrillation)
• Cardiac conduction abnormalities (e.g., congenital or acquired heart block)
• Uncorrected or ongoing serum electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia)
• Underlying pulmonary disease including asthma, emphysema, chronic bronchitis, pulmonary tuberculosis or any other structural or functional pulmonary condition (e.g., history of severe airway hyper-responsiveness).
• FEV1/FEV6 \< 0.73 as an indication of potential airflow limitation.
• Known allergy to excipients in the challenge virus inoculum and placebo. The excipient (diluent and placebo) is SPG: sucrose, KH2PO4, K2HPO4, L-glutamic acid.
• Moderate or severe symptoms of health anxiety, anxiety, and mood symptoms. Self-reported current diagnosis of a major psychiatric illness, including, but not limited to, a schizophrenia spectrum disorder, bipolar disorder, posttraumatic stress disorder, obsessive compulsive disorder, substance use disorder, or eating disorder, based on standardized mental health screening tools.
• Habitual\*\*\* smoker of tobacco, e-cigarettes or marijuana. \*\*\*Habitual smokers are those who smoke more than four cigarettes, other tobacco products, e-cigarettes (to include vaping and Juuling products) or marijuana in a week and cannot agree to abstain from smoking cigarettes, other tobacco products, e-cigarettes and/or marijuana products during participation in the study.
• Any current daily use of illicit drugs whereby the individual and/or study staff assess that the individual cannot abstain from during the isolation period.

Sponsors & Collaborators

• Canadian Center for Vaccinology: collaborator
• Dalhousie University: lead
• McGill University Health Centre/Research Institute of the McGill University Health Centre: collaborator

MeSH Terms

Conditions

Influenza, Human

Interventions

Influenza Vaccines

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Central Study Contacts

Nick Bartlett

CONTACT

902-470-8141; nicholas.bartlett@iwk.nshealth.ca

Hannah Munday

CONTACT

902-470-8141; hannah.munday@iwk.nshealth.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2025
• First Posted: December 26, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): January 31, 2028
• Last Updated: December 26, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share