Influenza
Conditions
Keywords
A/Texas/71/2017, Influenza, Influenza Challenge Study, Recombinant H3N2, Recombinant H3N2 Influenza Strain, Safety
Brief summary
An open-label, dose-ranging influenza challenge study in healthy adult volunteers to determine the optimal infection dose and safety of a recombinant H3N2 (A/Texas/ A/Texas/71/2017 (H3N2, clade 3C3a) influenza strain. The goal of this study is to find a challenge virus dose that is safe and can achieve a symptomatic influenza Attack Rate (AR) that will be sufficiently high for utilization in future vaccine or intervention studies. The optimal dose of the three considered is broadly defined as the minimum challenge virus dose that elicits the highest AR without meeting safety-stopping criteria. Additionally, viral recovery, clinical symptoms, and immune responses over the post-challenge period will be described by challenge dose group. This study will last for up to 1 year depending upon the number of challenge cohorts enrolled given the adaptive dose-escalation design. The populations are healthy males and non-pregnant, non-breastfeeding females aged = 18 and \< 46 years of age with a serum HAI antibody titer of \</=1:40 against influenza A/Texas/71/2017 (H3N2), clade 3C3a. The study will enroll and challenge up to 106 (plus 8 shams) healthy adult volunteers with the H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus challenge strain. The primary objectives are: 1) To determine the optimal infectious dose of a recombinant influenza virus (A/Texas/71/2017 (H3N2), clade 3C3a) to be used as a clinical challenge strain in future vaccine efficacy or intervention studies as assessed by viral shedding and clinical symptoms. 2) To describe viral detection by quantitative and qualitative Reverse Transcription - Polymerase Chain Reaction (RT-PCR) from study subjects at baseline and post-challenge. 3) To document clinical symptoms from self-reported surveys and standardized symptom scales at baseline and post-challenge.
Detailed description
An open-label, dose-ranging influenza challenge study in healthy adult volunteers to determine the optimal infection dose and safety of a recombinant H3N2 (A/Texas/ A/Texas/71/2017 (H3N2, clade 3C3a) influenza strain. The goal of this study is to find a challenge virus dose that is safe and can achieve a symptomatic influenza Attack Rate (AR) that will be sufficiently high for utilization in future vaccine or intervention studies. The optimal dose of the three considered is broadly defined as the minimum challenge virus dose that elicits the highest AR without meeting safety-stopping criteria. Additionally, viral recovery, clinical symptoms, and immune responses over the post-challenge period will be described by challenge dose group. This study will last for up to 1 year depending upon the number of challenge cohorts enrolled given the adaptive dose-escalation design. The populations are healthy males and non-pregnant, non-breastfeeding females aged = 18 and \< 46 years of age with a serum HAI antibody titer of \</=1:40 against influenza A/Texas/71/2017 (H3N2), clade 3C3a. The study will enroll and challenge up to 106 (plus 8 shams) healthy adult volunteers with the H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus challenge strain. Subjects will be pre-screened for study inclusion to have serological HAI antibody titers of \</=1:40 against the clinical challenge strain. Eligible participants will be enrolled sequentially into dosing cohorts and will be randomly assigned to receive a single dose of either placebo (sham inoculum) or a virus dose between 104 to 106 Median Issue Culture Infectious Dose (TCID50) (in an allocation of 1:12 to 1:17). Dose titration will be conducted under an adaptive escalation schedule whereby dosing will start at the lowest dose 104 TCID50 and only escalate to the next dose if a pre-determined infection and symptomatic attack rate are not met and the dose is determined to be safe and no pre-defined halting rule is met. The attack rate (AR), defined as the percentage of subjects meeting shedding and symptom criteria for symptomatic influenza virus infection (see clinical case definition below), will be determined for each challenge dose group in order to identify the optimal infectious dose (55%-80% AR). This adaptive, dose-ranging approach allows adjustments to challenge dose group size and escalation dose schedule to be informed by the AR and safety results. The primary objectives are: 1) To determine the optimal infectious dose1 of a recombinant influenza virus (A/Texas/71/2017 (H3N2), clade 3C3a) to be used as a clinical challenge strain in future vaccine efficacy or intervention studies as assessed by viral shedding and clinical symptoms. 2) To describe viral detection by quantitative and qualitative Reverse Transcription - Polymerase Chain Reaction (RT-PCR) from study subjects at baseline and post-challenge. 3) To document clinical symptoms from self-reported surveys and standardized symptom scales at baseline and post-challenge. The secondary objectives are: 1) To assess the safety profile of a live recombinant influenza strain (A/Texas/71/2017 (H3N2), clade 3C3a) following challenge in healthy adult volunteers. 2) To describe the host serum hemagglutination inhibition and microneutralization antibody responses at baseline and post-challenge. 3) To describe anti-Hemagglutination(HA)-stalk antibody titer at baseline and post-challenge.
Interventions
BIOLOGICALInfluenza RG-A/Texas/71/2017 (H3N2) Challenge
RG-A/Texas/71/2017 (H3N2) is an infectious influenza virus and requires handling at BioSafety Level 2. The challenge virus will be administered intranasally in a volume of approximately 0.5 mL per nostril. Intranasal challenge will be carried out using the Intranasal Mucosal Atomization ( MAD Nasa(TM)) Device attached to a 1 mL syringe.
OTHERPlacebo
Sucrose phosphate glutamate (SPG) inoculum
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Provide written informed consent prior to initiation of any study procedure 2. Are able to understand and comply with planned study procedures and be available for all study visits 3. Agree to remain an inpatient for at least 7 days after challenge AND until they have no viral shedding\*, determined by qualitative Reverse Transcription - Polymerase Chain Reaction (RT-PCR) beginning on Study Day 6 * No viral shedding is defined as two negative RT-PCR tests 12 or more hours apart 4. Healthy\* males and non-pregnant, non-breastfeeding females aged \> / = 18 and \< 46 years of age at enrollment \*Healthy is defined in inclusion criteria #11. NOTE: Female subjects of childbearing potential must have a negative serum pregnancy test at screening, a negative urine pregnancy test upon admission to the confinement unit AND a negative pregnancy test before any Chest x-ray (CXR) (if \> / = 7 days have passed since a serum pregnancy test). 5. Women of childbearing potential\* must agree to use or have practiced true abstinence\*\* or use at least one acceptable primary form of contraception\* for at least 30 days prior to challenge * Not of childbearing 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(R) 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 monogamous relationship with a vasectomized partner who has been vasectomized for 180 days or more prior to the subject receiving the influenza challenge virus, intrauterine devices, birth control pills, and injectable/implantable/insertable hormonal birth control products. Must use at least one acceptable primary form of contraception for at least 30 days prior to challenge and at least one acceptable primary form of contraception during the remainder of the study or approximately 57 days after confinement. NOTE: These criteria are applicable to female subjects in a heterosexual relationship AND of child-bearing potential. These criteria do not apply to subjects in a same sex relationship. 6. Non-habitual smoker\* of tobacco, e-cigarettes or marijuana \*Non-habitual smokers are those who smoke no more than four cigarettes, other tobacco products, e-cigarettes (to include vaping and Juuling products) or marijuana in a week and agree not to smoke cigarettes, other tobacco products, e-cigarettes and/or marijuana products during participation in the study. 7. No self-reported or known history of alcoholism within the last 2 years and agrees to abstain from alcohol for at least one week before admission and throughout the confinement period. 8. No self-reported or known history of restricted drug use\* for at least 30 days prior to challenge and agrees to abstain from restricted drugs for at least one week before admission and throughout the confinement period 9. Negative drug urine toxicology result on screening (i.e., amphetamines, cocaine, and opiates) and on admission to the confinement unit (i.e., amphetamines, cocaine, and opiates)\* \*Select drug use may be allowed at Investigator's discretion (e.g., prescribed amphetamines for ADHD) 10. Agree not to use the listed prescription or over the counter medications\* within 7 days prior to and through confinement period, 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) 11. In good health\*, and do not have clinically significant medical, psychiatric, chronic or intermittent health conditions including those listed in
Exclusion criteria
\*Good health, as determined by medical history, medication use and physical examination to evaluate ongoing chronic medical or psychiatric diagnoses or conditions, defined as those that have been present for at least 90 days, which would not affect the assessment of the safety of subjects or the immunogenicity of challenge. These medical diagnoses or conditions should be stable for the last 90 days (no hospitalizations, emergency room (ER) or urgent care for condition (excluding musculoskeletal conditions) and not listed in
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number and Percentage of Participants With Symptomatic Influenza Virus Infection After Challenge. | Day 2 through Day 8 | 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. |
| Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 1 through discharge from the inpatient unit (Day 8 to Day 10) | 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. |
| Mean Peak Viral Load (VL) After Challenge | Day 2 through Day 8 | 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. |
| Mean Duration of Viral Shedding | Day 2 through Day 8 | 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. |
| Mean Maximum Cumulative Modified Jackson Score (MJS) | Day 2 through Day 8 | 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. |
| Number and Percentage of Participants Symptomatic for Influenza. | Day 2 through Day 8 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number and Percentage of Participants With Serological Conversion for Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8, Day 15, and Day 29 | 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. |
| Geometric Mean Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day -1 (baseline), Day 8, Day 15, and Day 29 | 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. |
| Number of Adverse Events (AEs) Reported From Challenge Through Day 29 | Day 1 through Day 29 | 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. |
| Geometric Mean HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day -1 (baseline), Day 8, Day 15, and Day 29 | 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. |
| Number and Percentage of Participants With Serological Conversion for HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8, Day 15, and Day 29 | 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. |
| Number and Percentage of Participants Reporting Any AE From Challenge Through Day 29. | Day 1 through Day 29 | 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. |
| Number of Serious Adverse Events (SAEs) Reported From Challenge Through Day 57 | Day 1 through Day 57 | 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. |
| Number and Percentage of Participants Reporting an SAE at Any Time From Challenge Through Day 57 | Day 1 through Day 57 | 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. |
| Number and Percentage of Participants With Serological Conversion for Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8, Day 15, and Day 29 | 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. |
| Geometric Mean Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day -1 (baseline), Day 8, Day 15, and Day 29 | 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. |
Countries
United States
Participant flow
Recruitment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 10^4 TCID50 Challenge Virus Cohort 1A: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10\^4 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1.
Cohorts 1B and 1C were not enrolled; after review by the Internal Safety Review Committee (ISRC), enrollment continued into Cohort 2A. | 12 |
| 10^5 TCID50 Challenge Virus Cohort 2A: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10\^5 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1.
Cohorts 2B and 2C were not enrolled; after review by the Internal Safety Review Committee (ISRC), enrollment continued into Cohort 3A. | 10 |
| 10^6 TCID50 Challenge Virus Cohorts 3A and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of 10\^6 TCID50 of recombinant H3N2 (A/Texas/71/2017 (H3N2), clade 3C3a) influenza virus on Day 1. | 36 |
| Sham Inoculum From Cohorts 1A, 2A, 3A, and 3B: Participants were intranasally administered 1.0 mL (0.5mL per nostril) of sham sucrose phosphate glutamate (SPG) inoculum on Day 1. | 2 |
| Total | 60 |
Baseline characteristics
| Characteristic | 10^4 TCID50 Challenge Virus | 10^5 TCID50 Challenge Virus | 10^6 TCID50 Challenge Virus | Sham Inoculum | Total |
|---|---|---|---|---|---|
| Age, Continuous | 33.8 years STANDARD_DEVIATION 5.8 | 37.8 years STANDARD_DEVIATION 6.5 | 31.0 years STANDARD_DEVIATION 6 | 30.5 years STANDARD_DEVIATION 2.1 | 32.7 years STANDARD_DEVIATION 6.4 |
| BMI | 26.08 kg/m^2 STANDARD_DEVIATION 4.41 | 30.07 kg/m^2 STANDARD_DEVIATION 5.99 | 28.24 kg/m^2 STANDARD_DEVIATION 4.36 | 23.80 kg/m^2 STANDARD_DEVIATION 0.85 | 27.97 kg/m^2 STANDARD_DEVIATION 4.74 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 8 Participants | 0 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 8 Participants | 28 Participants | 2 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 14 Participants | 0 Participants | 20 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 6 Participants | 18 Participants | 2 Participants | 34 Participants |
| Region of Enrollment United States | 12 Participants | 10 Participants | 36 Participants | 2 Participants | 60 Participants |
| Sex: Female, Male Female | 5 Participants | 7 Participants | 13 Participants | 1 Participants | 26 Participants |
| Sex: Female, Male Male | 7 Participants | 3 Participants | 23 Participants | 1 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 10 | 0 / 36 | 0 / 2 |
| other Total, other adverse events | 6 / 12 | 8 / 10 | 17 / 36 | 2 / 2 |
| serious Total, serious adverse events | 0 / 12 | 0 / 10 | 0 / 36 | 0 / 2 |
Outcome results
Primary
Mean Duration of Viral Shedding
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.
Time frame: Day 2 through Day 8
Population: The Safety population consists of all participants who received study influenza challenge or sham inoculum. This analysis includes all participants in the Safety population who completed the inpatient period.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 10^4 TCID50 Challenge Virus | Mean Duration of Viral Shedding | 2.3 days |
| 10^5 TCID50 Challenge Virus | Mean Duration of Viral Shedding | 3.8 days |
| 10^6 TCID50 Challenge Virus | Mean Duration of Viral Shedding | 4.4 days |
| Sham Inoculum | Mean Duration of Viral Shedding | NA days |
Primary
Mean Maximum Cumulative Modified Jackson Score (MJS)
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.
Time frame: Day 2 through Day 8
Population: The Safety population consists of all participants who received study influenza challenge or sham inoculum.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 10^4 TCID50 Challenge Virus | Mean Maximum Cumulative Modified Jackson Score (MJS) | 13 score on a scale |
| 10^5 TCID50 Challenge Virus | Mean Maximum Cumulative Modified Jackson Score (MJS) | 15.9 score on a scale |
| 10^6 TCID50 Challenge Virus | Mean Maximum Cumulative Modified Jackson Score (MJS) | 25.8 score on a scale |
| Sham Inoculum | Mean Maximum Cumulative Modified Jackson Score (MJS) | 1.0 score on a scale |
Primary
Mean Peak Viral Load (VL) After Challenge
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.
Time frame: Day 2 through Day 8
Population: The Safety population consists of all participants who received study influenza challenge or sham inoculum. This analysis includes all participants in the Safety population who completed the inpatient period.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| 10^4 TCID50 Challenge Virus | Mean Peak Viral Load (VL) After Challenge | 1.2154 log-10 viral copies/mL |
| 10^5 TCID50 Challenge Virus | Mean Peak Viral Load (VL) After Challenge | 2.6931 log-10 viral copies/mL |
| 10^6 TCID50 Challenge Virus | Mean Peak Viral Load (VL) After Challenge | 2.6570 log-10 viral copies/mL |
| Sham Inoculum | Mean Peak Viral Load (VL) After Challenge | NA log-10 viral copies/mL |
Primary
Number and Percentage of Participants Symptomatic for Influenza.
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.
Time frame: Day 2 through Day 8
Population: The Safety population consists of all participants who received study influenza challenge or sham inoculum.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 10^4 TCID50 Challenge Virus | Number and Percentage of Participants Symptomatic for Influenza. | 8 Participants |
| 10^5 TCID50 Challenge Virus | Number and Percentage of Participants Symptomatic for Influenza. | 6 Participants |
| 10^6 TCID50 Challenge Virus | Number and Percentage of Participants Symptomatic for Influenza. | 29 Participants |
| Sham Inoculum | Number and Percentage of Participants Symptomatic for Influenza. | 0 Participants |
Primary
Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge.
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.
Time frame: Day 1 through discharge from the inpatient unit (Day 8 to Day 10)
Population: The Safety population consists of all participants who received study influenza challenge or sham inoculum.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 10^4 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 8+ | 3 Participants |
| 10^4 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 6 | 4 Participants |
| 10^4 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 2 | 4 Participants |
| 10^4 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 4 | 3 Participants |
| 10^4 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 1 | 0 Participants |
| 10^4 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 5 | 5 Participants |
| 10^4 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 3 | 2 Participants |
| 10^4 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 7 | 3 Participants |
| 10^5 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 3 | 6 Participants |
| 10^5 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 4 | 7 Participants |
| 10^5 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 8+ | 2 Participants |
| 10^5 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 1 | 0 Participants |
| 10^5 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 7 | 5 Participants |
| 10^5 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 2 | 4 Participants |
| 10^5 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 6 | 5 Participants |
| 10^5 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 5 | 7 Participants |
| 10^6 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 3 | 32 Participants |
| 10^6 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 7 | 12 Participants |
| 10^6 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 1 | 0 Participants |
| 10^6 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 2 | 34 Participants |
| 10^6 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 4 | 29 Participants |
| 10^6 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 5 | 23 Participants |
| 10^6 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 6 | 15 Participants |
| 10^6 TCID50 Challenge Virus | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 8+ | 7 Participants |
| Sham Inoculum | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 6 | 0 Participants |
| Sham Inoculum | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 5 | 0 Participants |
| Sham Inoculum | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 1 | 0 Participants |
| Sham Inoculum | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 7 | 0 Participants |
| Sham Inoculum | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 8+ | 0 Participants |
| Sham Inoculum | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 4 | 0 Participants |
| Sham Inoculum | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 3 | 0 Participants |
| Sham Inoculum | Number and Percentage of Participants With Detected Viral Shedding in Nasopharyngeal (NP) Swabs Each Day Post-challenge. | Day 2 | 0 Participants |
Primary
Number and Percentage of Participants With Symptomatic Influenza Virus Infection After Challenge.
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.
Time frame: Day 2 through Day 8
Population: The Safety population consists of all participants who received study influenza challenge or sham inoculum.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 10^4 TCID50 Challenge Virus | Number and Percentage of Participants With Symptomatic Influenza Virus Infection After Challenge. | 4 Participants |
| 10^5 TCID50 Challenge Virus | Number and Percentage of Participants With Symptomatic Influenza Virus Infection After Challenge. | 5 Participants |
| 10^6 TCID50 Challenge Virus | Number and Percentage of Participants With Symptomatic Influenza Virus Infection After Challenge. | 28 Participants |
| Sham Inoculum | Number and Percentage of Participants With Symptomatic Influenza Virus Infection After Challenge. | 0 Participants |
Secondary
Geometric Mean HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day
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.
Time frame: Day -1 (baseline), Day 8, Day 15, and Day 29
Population: The Intent-to-Treat population consists of all enrolled participants
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| 10^4 TCID50 Challenge Virus | Geometric Mean HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day -1 | 9407.9 titer |
| 10^4 TCID50 Challenge Virus | Geometric Mean HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 9175.2 titer |
| 10^4 TCID50 Challenge Virus | Geometric Mean HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 10964.6 titer |
| 10^4 TCID50 Challenge Virus | Geometric Mean HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 11227.9 titer |
| 10^5 TCID50 Challenge Virus | Geometric Mean HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 8904.9 titer |
| 10^5 TCID50 Challenge Virus | Geometric Mean HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 16736.1 titer |
| 10^5 TCID50 Challenge Virus | Geometric Mean HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 19814.9 titer |
| 10^5 TCID50 Challenge Virus | Geometric Mean HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day -1 | 5722.8 titer |
| 10^6 TCID50 Challenge Virus | Geometric Mean HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day -1 | 7938.6 titer |
| 10^6 TCID50 Challenge Virus | Geometric Mean HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 13989.0 titer |
| 10^6 TCID50 Challenge Virus | Geometric Mean HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 14693.3 titer |
| 10^6 TCID50 Challenge Virus | Geometric Mean HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 10506.4 titer |
| Sham Inoculum | Geometric Mean HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 7927.4 titer |
| Sham Inoculum | Geometric Mean HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day -1 | 7954.3 titer |
| Sham Inoculum | Geometric Mean HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 7752.2 titer |
| Sham Inoculum | Geometric Mean HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 9238.5 titer |
Secondary
Geometric Mean Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day
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.
Time frame: Day -1 (baseline), Day 8, Day 15, and Day 29
Population: The Intent-to-Treat population consists of all enrolled participants.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| 10^4 TCID50 Challenge Virus | Geometric Mean Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day -1 | 10.9 titer |
| 10^4 TCID50 Challenge Virus | Geometric Mean Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 11.2 titer |
| 10^4 TCID50 Challenge Virus | Geometric Mean Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 25.2 titer |
| 10^4 TCID50 Challenge Virus | Geometric Mean Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 25.7 titer |
| 10^5 TCID50 Challenge Virus | Geometric Mean Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 8.7 titer |
| 10^5 TCID50 Challenge Virus | Geometric Mean Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 36.1 titer |
| 10^5 TCID50 Challenge Virus | Geometric Mean Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 32.5 titer |
| 10^5 TCID50 Challenge Virus | Geometric Mean Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day -1 | 7.6 titer |
| 10^6 TCID50 Challenge Virus | Geometric Mean Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 37.0 titer |
| 10^6 TCID50 Challenge Virus | Geometric Mean Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 15.9 titer |
| 10^6 TCID50 Challenge Virus | Geometric Mean Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 33.8 titer |
| 10^6 TCID50 Challenge Virus | Geometric Mean Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day -1 | 10.7 titer |
| Sham Inoculum | Geometric Mean Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 5.0 titer |
| Sham Inoculum | Geometric Mean Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 5.0 titer |
| Sham Inoculum | Geometric Mean Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day -1 | 5.0 titer |
| Sham Inoculum | Geometric Mean Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 5.0 titer |
Secondary
Geometric Mean Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day
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.
Time frame: Day -1 (baseline), Day 8, Day 15, and Day 29
Population: The Intent-to-Treat population consists of all enrolled participants
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| 10^4 TCID50 Challenge Virus | Geometric Mean Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day -1 | 29.1 titer |
| 10^4 TCID50 Challenge Virus | Geometric Mean Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 37.8 titer |
| 10^4 TCID50 Challenge Virus | Geometric Mean Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 69.2 titer |
| 10^4 TCID50 Challenge Virus | Geometric Mean Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 64.2 titer |
| 10^5 TCID50 Challenge Virus | Geometric Mean Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 28.3 titer |
| 10^5 TCID50 Challenge Virus | Geometric Mean Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 102.0 titer |
| 10^5 TCID50 Challenge Virus | Geometric Mean Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 82.8 titer |
| 10^5 TCID50 Challenge Virus | Geometric Mean Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day -1 | 16.2 titer |
| 10^6 TCID50 Challenge Virus | Geometric Mean Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 85.7 titer |
| 10^6 TCID50 Challenge Virus | Geometric Mean Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 46.9 titer |
| 10^6 TCID50 Challenge Virus | Geometric Mean Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 75.4 titer |
| 10^6 TCID50 Challenge Virus | Geometric Mean Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day -1 | 24.0 titer |
| Sham Inoculum | Geometric Mean Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 14.1 titer |
| Sham Inoculum | Geometric Mean Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 23.8 titer |
| Sham Inoculum | Geometric Mean Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day -1 | 14.1 titer |
| Sham Inoculum | Geometric Mean Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 20.0 titer |
Secondary
Number and Percentage of Participants Reporting an SAE at Any Time From Challenge Through Day 57
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.
Time frame: Day 1 through Day 57
Population: The Safety population consists of all participants who received study influenza challenge or sham inoculum.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 10^4 TCID50 Challenge Virus | Number and Percentage of Participants Reporting an SAE at Any Time From Challenge Through Day 57 | 0 Participants |
| 10^5 TCID50 Challenge Virus | Number and Percentage of Participants Reporting an SAE at Any Time From Challenge Through Day 57 | 0 Participants |
| 10^6 TCID50 Challenge Virus | Number and Percentage of Participants Reporting an SAE at Any Time From Challenge Through Day 57 | 0 Participants |
| Sham Inoculum | Number and Percentage of Participants Reporting an SAE at Any Time From Challenge Through Day 57 | 0 Participants |
Secondary
Number and Percentage of Participants Reporting Any AE From Challenge Through Day 29.
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.
Time frame: Day 1 through Day 29
Population: The Safety population consists of all participants who received study influenza challenge or sham inoculum.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 10^4 TCID50 Challenge Virus | Number and Percentage of Participants Reporting Any AE From Challenge Through Day 29. | 6 Participants |
| 10^5 TCID50 Challenge Virus | Number and Percentage of Participants Reporting Any AE From Challenge Through Day 29. | 8 Participants |
| 10^6 TCID50 Challenge Virus | Number and Percentage of Participants Reporting Any AE From Challenge Through Day 29. | 17 Participants |
| Sham Inoculum | Number and Percentage of Participants Reporting Any AE From Challenge Through Day 29. | 2 Participants |
Secondary
Number and Percentage of Participants With Serological Conversion for HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day
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.
Time frame: Day 8, Day 15, and Day 29
Population: The Intent-to-Treat population consists of all enrolled participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 10^4 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 0 Participants |
| 10^4 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 0 Participants |
| 10^4 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 1 Participants |
| 10^5 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 2 Participants |
| 10^5 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 2 Participants |
| 10^5 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 3 Participants |
| 10^6 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 2 Participants |
| 10^6 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 0 Participants |
| 10^6 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 2 Participants |
| Sham Inoculum | Number and Percentage of Participants With Serological Conversion for HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 0 Participants |
| Sham Inoculum | Number and Percentage of Participants With Serological Conversion for HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 0 Participants |
| Sham Inoculum | Number and Percentage of Participants With Serological Conversion for HA-stalk-specific Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 0 Participants |
Secondary
Number and Percentage of Participants With Serological Conversion for Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day
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.
Time frame: Day 8, Day 15, and Day 29
Population: The Intent-to-Treat population consists of all enrolled participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 10^4 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 1 Participants |
| 10^4 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 2 Participants |
| 10^4 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 0 Participants |
| 10^5 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 1 Participants |
| 10^5 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 4 Participants |
| 10^5 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 4 Participants |
| 10^6 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 14 Participants |
| 10^6 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 14 Participants |
| 10^6 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 4 Participants |
| Sham Inoculum | Number and Percentage of Participants With Serological Conversion for Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 0 Participants |
| Sham Inoculum | Number and Percentage of Participants With Serological Conversion for Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 0 Participants |
| Sham Inoculum | Number and Percentage of Participants With Serological Conversion for Hemagglutination Inhibition (HAI) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 0 Participants |
Secondary
Number and Percentage of Participants With Serological Conversion for Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day
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.
Time frame: Day 8, Day 15, and Day 29
Population: The Intent-to-Treat population consists of all enrolled participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 10^4 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 0 Participants |
| 10^4 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 3 Participants |
| 10^4 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 4 Participants |
| 10^5 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 0 Participants |
| 10^5 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 6 Participants |
| 10^5 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 7 Participants |
| 10^6 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 17 Participants |
| 10^6 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 5 Participants |
| 10^6 TCID50 Challenge Virus | Number and Percentage of Participants With Serological Conversion for Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 17 Participants |
| Sham Inoculum | Number and Percentage of Participants With Serological Conversion for Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 8 | 0 Participants |
| Sham Inoculum | Number and Percentage of Participants With Serological Conversion for Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 29 | 0 Participants |
| Sham Inoculum | Number and Percentage of Participants With Serological Conversion for Microneutralization (MN) Antibody Titers Against A/Texas/71/2017 (H3N2), Clade 3C3a Virus, by Study Day | Day 15 | 0 Participants |
Secondary
Number of Adverse Events (AEs) Reported From Challenge Through Day 29
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.
Time frame: Day 1 through Day 29
Population: The Safety population consists of all participants who received study influenza challenge or sham inoculum.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 10^4 TCID50 Challenge Virus | Number of Adverse Events (AEs) Reported From Challenge Through Day 29 | 10 events |
| 10^5 TCID50 Challenge Virus | Number of Adverse Events (AEs) Reported From Challenge Through Day 29 | 16 events |
| 10^6 TCID50 Challenge Virus | Number of Adverse Events (AEs) Reported From Challenge Through Day 29 | 28 events |
| Sham Inoculum | Number of Adverse Events (AEs) Reported From Challenge Through Day 29 | 3 events |
Secondary
Number of Serious Adverse Events (SAEs) Reported From Challenge Through Day 57
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.
Time frame: Day 1 through Day 57
Population: The Safety population consists of all participants who received study influenza challenge or sham inoculum.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 10^4 TCID50 Challenge Virus | Number of Serious Adverse Events (SAEs) Reported From Challenge Through Day 57 | 0 events |
| 10^5 TCID50 Challenge Virus | Number of Serious Adverse Events (SAEs) Reported From Challenge Through Day 57 | 0 events |
| 10^6 TCID50 Challenge Virus | Number of Serious Adverse Events (SAEs) Reported From Challenge Through Day 57 | 0 events |
| Sham Inoculum | Number of Serious Adverse Events (SAEs) Reported From Challenge Through Day 57 | 0 events |