Influenza A H3N2
Conditions
Keywords
Influenza, Flu, H3N2, Human Challenge Trial
Brief summary
An Exploratory Study to Establish the Dose, Safety and Pathogenicity of a New Influenza A H3N2 Challenge Strain in Healthy Participants 18 to 55 Years of Age In Part A, up to 40 participants will be randomly allocated to one of two groups to be given one of two virus doses (Virus Dose 1 or Virus Dose 2). Based on the outcome of Part A, participants in Part B, may be given Virus Dose 1, Virus Dose 2, or another virus dose (e.g., Virus Dose 3)
Detailed description
This is an exploratory study of an influenza A/England/7763/2022 H3N2 challenge strain, to determine the optimum safe infectious titer of challenge agent, in healthy participants 18 to 55 years of age. A total of up to 80 participants may be given the influenza A/England/7763/2022 H3N2 challenge agent. Each participant will remain in the study for approximately 4 months from screening to the last clinic visit. The study will consist of 2 parts, in Part A of the study, up to 40 participants will be randomly allocated to one of two groups to be given one of two virus doses (Virus Dose 1 or Virus Dose 2). Based on the outcome of Part A, additional participants may be enrolled into the optional Part B of the study and may be given Virus Dose 1, Virus Dose 2, and/or another virus dose (e.g., Virus Dose 3) The study is divided into three phases: 1. Screening phase: Screening will occur between Day -90 to Day -2/-1. 2. Quarantine phase: Participants will stay in the quarantine unit for approximately 8 days (from Day -2/-1 to Day 8). One or two days prior to the day of inoculation with the challenge virus, participants will be admitted to quarantine where their eligibility will be reassessed. If participants remain eligible for the study, they will receive the challenge virus on Day 0. Participants will undergo a range of clinical assessments and safety monitoring for the entirety of their stay in quarantine. Participants will be discharged from the quarantine unit on Day 8 (or may remain longer at the principal investigator's discretion). 3. Outpatient phase: Following the conclusion of the quarantine phase, participants will attend a Follow-Up visit, approximately 28 days after they received the study virus. Their symptoms will be reassessed, and a complete safety examination performed.
Interventions
OTHERInfluenza A H3N2 virus dose arm 1
Medium dose, approximately 10\^4.5 TCID50/mL
OTHERInfluenza A H3N2 virus dose arm 2
High dose, approximately 10\^5.5 TCID50/mL
OTHERInfluenza A H3N2 virus dose arm 3
TBD, depending on outcome of Part A
Sponsors
Hvivo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Written informed consent * Adult male or female aged between 18 and 55 years * A total body weight ≥50 kg and body mass index (BMI) ≥18 kg/m2 and ≤35kg/m2. * In good health with no history, or current evidence, of clinically significant medical conditions, and no clinically significant test abnormalities that will interfere with participant safety. * Documented medical history * Adherence to contraception requirements * Serosuitable for the challenge virus
Exclusion criteria
* History of, or currently active, symptoms or signs suggestive of upper or lower respiratory tract (LRT) infection within 4 weeks prior to the first study visit. * Any history or evidence of any clinically significant or currently active disease. * Any participants who have smoked ≥10 pack years at any time. * Female participants who are breastfeeding, or have been pregnant within 6 months prior to the study, or have a positive pregnancy test at any point during screening or prior to inoculation. * Any history of anaphylaxis and/or a any history of severe allergic reaction. * Venous access deemed inadequate for the phlebotomy and cannulation demands of the study. * Lifetime history of anaphylaxis and/or a lifetime history of severe allergic reaction. * Significant abnormality of the nose, includes loss of or alterations in smell or taste, nasal polyps, epistaxis, nasal or sinus surgery. * Recent vaccinations or intention to receive vaccination before the Day 28 follow up visit. * Receipt of blood or blood products, or loss (including blood donations) of 550 mL or more of blood during the 3 months prior to the planned inoculation or planned during the 3 months after the final visit. * Recent receipt of investigational drugs or challenge viruses. * Use or anticipated use during the conduct of the study of concomitant medications (prescription and/or non-prescription), including vitamins or herbal and dietary supplements within the specified windows. * Positive drugs of abuse test, recent history or presence of alcohol addiction, excessive consumption of xanthine containing substances or a presence of significant signs and symptoms of nicotine withdrawal on first study visit. * A forced expiratory volume in 1 second (FEV1) \<80%. * Positive HIV, hepatitis B virus, or hepatitis C virus test. * Presence of fever, defined as participant presenting with a temperature reading of ≥37.9°C on Day -2/-1 and/or pre-inoculation on Day 0. * Those employed or immediate relatives of those employed at hVIVO or the sponsor. * Any other reason, in the opinion of the investigator deems the participant unsuitable for the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of Adverse Events Related to the Viral Challenge | Day 0 to Day 28 | Occurrence of adverse events (AEs) related to the viral challenge from viral challenge (Day 0) to the Day 28 follow-up visit. |
| Occurrence of Serious Adverse Events Related to the Viral Challenge | Day 0 to Day 28 | Occurrence of serious adverse events (SAEs) related to the viral challenge from viral challenge (Day 0) to the Day 28 follow-up visit. |
| Induces Laboratory-confirmed Infection in ≥40% of Inoculated Participants | Day 1 to Day 8 | Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR)-confirmed influenza infection, defined as 2 quantifiable (≥ lower limit of quantification \[LLOQ\]) qRT-PCR measurements (reported over 4 planned consecutive assessments within 48 hours), from Day 1 pm to planned discharge from quarantine (Day 8 am). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Viral Culture-confirmed Influenza Infection. | Day 1 to Day 8 | Viral culture-confirmed influenza infection, defined as a quantifiable viral culture measurement, from Day 1 pm to planned discharge from quarantine (Day 8 am). |
| VL-AUC of Influenza Challenge Virus as Determined by qRT-PCR | Day 1 to Day 8 | Area under the viral load-time curve (VL-AUC) of influenza challenge virus as determined by qRT-PCR on both nasal and throat (Part B only) samples, starting from Day 1 pm up to planned discharge from quarantine (Day 8 am) |
| Peak Viral Load of Influenza Challenge Virus as Determined by qRT-PCR | Day 1 to Day 8 | Peak viral load of influenza challenge virus defined as the maximum viral load, from qRT-PCR on nasal and throat (Part B only) samples from Day 1 pm to planned discharge from quarantine (Day 8 am). |
| VL-AUC of Influenza Challenge Virus as Determined by Viral Culture | Day 1 to Day 8 | Area under the viral load-time curve (VL-AUC) of influenza challenge virus as determined by viral culture on both nasal and throat (Part B only) samples, starting from Day 1 pm up to planned discharge from quarantine (Day 8 am) |
| Peak Viral Load of Influenza Challenge Virus as Determined by Viral Culture | Day 1 to Day 8 | Peak viral load of influenza challenge virus defined as the maximum viral load, from by viral culture on nasal and throat (Part B only) samples from Day 1 pm to planned discharge from quarantine (Day 8 am). |
| Area Under the Total Clinical Symptoms Score-time Curve (TSS-AUC) | Day 1 to Day 8 | Data presented is score\*days. TSS-AUC (trapezium rule) as measured by graded symptom scoring system collected 3 times daily starting Day 1 am up to Day 8 am using a participant self-reportable 13-symptoms card, the max number of diary cards included in the AUC calculation is 22, the maximum time period is 7 days. Clinical symptoms included runny nose, stuffy nose, sneezing, sore throat, earache, malaise/tiredness, headache, muscle and/or joint ache, chilliness/feverishness, cough, chest tightness, shortness of breath, and wheeze. Participants scored symptom from 0 (no symptoms) to 3 (severe). Shortness of breath and wheeze had an additional scoring option of grade 4. Dairy card total symptom scores ranged from 0 (if all symptoms graded 0) to 41 (if all symptoms graded 3 and shortness of breath and wheeze graded 4). The range of TSS AUC scores are between 0 and 287 score\*days (maximum of 41\*7). |
| Peak Total Symptoms Diary Card Score | Day 1 to Day 8 | Peak Total Symptom Score (TSS) for each participant is defined as the diary card total with the worst score (highest). The symptom scoring system was collected three times daily starting one day post-viral challenge (Day 1) up to discharge from quarantine (Day 8 am) using a participant self-reportable 13-symptoms card. Clinical symptoms included runny nose, stuffy nose, sneezing, sore throat, earache, malaise/tiredness, headache, muscle and/or joint ache, chilliness/feverishness, cough, chest tightness, shortness of breath, and wheeze. Participants scored symptom from 0 (no symptoms) to 3 (severe). Shortness of breath and wheeze had an additional scoring option of grade 4. Dairy card total symptom scores ranged from 0 (if all symptoms graded 0) to 41 (if all symptoms graded 3 and shortness of breath and wheeze graded 4). |
| Peak Daily Symptoms Diary Card Score | Day 1 to Day 8 | Peak daily symptom score was derived, for each day from Day 1 to Day 8, as the maximum of the 3 total symptoms scores on that day. The symptoms were collected three times daily starting one day post-viral challenge (Day 1) up to planned discharge from quarantine (Day 8 am) using a participant self-reportable 13-symptoms card. Clinical symptoms included runny nose, stuffy nose, sneezing, sore throat, earache, malaise/tiredness, headache, muscle and/or joint ache, chilliness/feverishness, cough, chest tightness, shortness of breath, and wheeze. Participants scored symptom from 0 (no symptoms) to 3 (severe). Shortness of breath and wheeze had an additional scoring option of grade 4. Dairy card total symptom scores ranged from 0 (if all symptoms graded 0) to 41 (if all symptoms graded 3 and shortness of breath and wheeze graded 4). |
| Laboratory-confirmed Febrile Influenza Infection | Day 1 to Day 8 | A qRT-PCR-confirmed influenza infection, defined as 2 quantifiable (≥LLOQ) qRT-PCR measurements (reported on 2 or more independent samples over 4 planned consecutive assessments within 48 hours), from Day 1 pm to planned discharge from quarantine (Day 8 am) AND, a febrile episode, defined as a temperature of ≥37.9°C, from Day 1 am to planned discharge from quarantine (Day 8 am). |
| qRT-PCR-confirmed Influenza-like Illness (Centers for Disease and Control [CDC]) | Day 1 to Day 8 | A qRT-PCR-confirmed influenza infection, defined as 2 quantifiable (≥LLOQ) qRT-PCR measurements (reported on 2 or more independent samples over 4 planned consecutive assessments within 48 hours), from Day 1 pm to planned discharge from quarantine (Day 8 am) AND, a febrile episode, defined as a temperature of ≥37.8ºC, and a cough and/or sore throat (symptoms and signs), from Day 1 am to planned discharge from quarantine (Day 8 am), in the absence of a known cause other than influenza. |
| qRT-PCR-confirmed Influenza-like Illness (World Health Organization [WHO]) | Day 1 to Day 8 | A qRT-PCR-confirmed influenza infection, defined as 2 quantifiable (≥LLOQ) qRT-PCR measurements (reported on 2 or more independent samples over 4 planned consecutive assessments within 48 hours), from Day 1 pm to planned discharge from quarantine (Day 8 am) AND, a febrile episode, defined as a temperature of ≥38.0ºC and a cough, from Day 1 am to planned discharge from quarantine (Day 8 am). |
| Laboratory-confirmed Moderately Severe Symptomatic Influenza Infection | Day 1 to Day 8 | A qRT-PCR-confirmed influenza infection, defined as 2 quantifiable (≥LLOQ) qRT-PCR measurements (reported on 2 or more independent samples over 4 planned consecutive assessments within 48 hours), from Day 1 pm to planned discharge from quarantine (Day 8 am) AND, any symptoms from the symptom diary card of grade ≥2 at a single time point, from Day 1 am to planned discharge from quarantine (Day 8 am). |
| Laboratory-confirmed Symptomatic Influenza Infection | Day 1 to Day 8 | A qRT-PCR-confirmed influenza infection, defined as 2 quantifiable (≥LLOQ) qRT-PCR measurements (reported on 2 or more independent samples over 4 planned consecutive assessments within 48 hours), from Day 1 pm to planned discharge from quarantine (Day 8 am) AND, a total symptom score of ≥2 at a single time point, from Day 1 am to planned discharge from quarantine (Day 8 am). |
| Viral Culture Laboratory-confirmed Moderately Severe Symptomatic Influenza Infection | Day 1 to Day 8 | Viral culture laboratory-confirmed infection, AND any symptoms from the symptom diary card of grade ≥2 at a single time point, from Day 1 am to planned discharge from quarantine (Day 8 am). |
Countries
United Kingdom
Contacts
PRINCIPAL_INVESTIGATORAlexandre Lima, MD-PhD
hVIVO Services Ltd.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 29.60 years STANDARD_DEVIATION 7.92 |
| Body Mass Index (BMI) | 27.18 kg/m^2 STANDARD_DEVIATION 3.14 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants |
| Race/Ethnicity, Customized Multiple | 1 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 24 Participants |
| Region of Enrollment United Kingdom | 5 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 4 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 / 5 | 0 / 5 | 0 / 4 | 0 / 19 |
| other Total, other adverse events | 0 / 5 | 4 / 5 | 2 / 4 | 9 / 19 |
| serious Total, serious adverse events | 0 / 5 | 0 / 5 | 0 / 4 | 0 / 19 |
Outcome results
None listed