Trial Outcomes & Findings for Influenza Challenge Study to Determine the Optimal Infection Dose and Safety of a Recombinant H3N2 (A/Texas/71/2017 (H3N2, Clade 3C3a) Influenza Strain (NCT NCT04978454)

Participants were healthy adult volunteers meeting all protocol-defined eligibility criteria. Participants were recruited from the existing cohort that were pre-screened for influenza antibody titers in the screening protocol DMID 20-0004, as well as from other existing participant registries, through advertising, and by word of mouth. Enrollment occurred between 19AUG2021 and 21JUL2022.

Influenza Challenge Study to Determine the Optimal Infection Dose and Safety of a Recombinant H3N2 (A/Texas/71/2017 (H3N2, Clade 3C3a) Influenza Strain

Symptomatic influenza virus infection is defined as meeting both of the following criteria: 1. Viral shedding (as determined by a positive qualitative RT-PCR result or a detectable quantitative RT-PCR result) on at least two days beginning 24 hours after challenge until Study Day 8. 2. A cumulative symptom score = 6 from daily component symptoms computed across any consecutive 5-day window through Day 8 beginning on Day 2 post challenge using a Modified Jackson Score (MJS). MJS ranges from 0 to 36, with higher scores corresponding to worse outcomes.

Viral shedding status (yes/no) is determined by at least one of: a positive qualitative reverse transcription-polymerase chain reaction (RT-PCR) result from multiplex assay, or a detectable quantitative RT-PCR result.

The magnitude of viral shedding is measured via quantitative RT-PCR. Peak VL post-challenge is computed for each participant as the maximum log-10 viral copies/mL.

Viral shedding status (yes/no) for each day during the challenge period is determined by at least one of: a positive qualitative RT-PCR result from multiplex assay, or a detectable quantitative RT-PCR result. The duration of shedding for each participant was computed as the number of days from the initial positive NP swab until the day after the final positive NP swab. Intermittent negative results were ignored for this computation.

The cumulative symptom score from daily component symptoms is computed across any consecutive 5-day window through Day 8 beginning on Day 2 post challenge using the Modified Jackson Score (MJS). MJS ranges from 0 to 36, with higher scores corresponding to worse outcomes. The maximum cumulative score post-challenge was computed for each participant.

Participants were categorized as symptomatic if they reported a cumulative symptom score = 6 from daily component symptoms computed across any consecutive 5-day window through Day 8 beginning on Day 2 post challenge using a Modified Jackson Score (MJS). MJS ranges from 0 to 36, with higher scores corresponding to worse outcomes.

Adverse events were defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of medicinal (investigational) product. Non-serious, unsolicited adverse events were collected from Day 1 through Day 29. Serious adverse events were collected from Day 1 through Day 57. Adverse events were MedDRA coded.

Adverse events were defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of medicinal (investigational) product. Non-serious, unsolicited adverse events were collected from Day 1 through Day 29. Serious adverse events were collected from Day 1 through Day 57. Adverse events were MedDRA coded.

An adverse event or suspected adverse reaction is considered "serious" if, in the view of either the investigator or sponsor, it results in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.

An adverse event or suspected adverse reaction is considered "serious" if, in the view of either the investigator or sponsor, it results in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered serious when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.

Serological conversion (seroconversion) is defined as a minimum 4-fold rise in post-challenge antibody titers, compared to baseline. Titers for each participant are estimated as the geometric mean of technical replicate results, and the geometric mean is taken again across participants in each challenge dose group.

Titers for each participant are estimated as the geometric mean of technical replicate results, and the geometric mean is taken again across participants in each challenge dose group.

Serological conversion (seroconversion) is defined as a minimum 4-fold rise in post-challenge antibody titers, compared to baseline. Titers for each participant are estimated as the geometric mean of technical replicate results, and the geometric mean is taken again across participants in each challenge dose group.

Titers for each participant are estimated as the geometric mean of technical replicate results, and the geometric mean is taken again across participants in each challenge dose group.

Serological conversion (seroconversion) is defined as a minimum 4-fold rise in post-challenge antibody titers against HA group 2 stem domains, compared to baseline. Titers for each participant are estimated as the geometric mean of technical replicate results, and the geometric mean is taken again across participants in each challenge dose group.

Titers for each participant are estimated as the geometric mean of technical replicate results, and the geometric mean is taken again across participants in each challenge dose group.