Dose, Safety, and Pathogenicity of a New Influenza A H3N2 Challenge Strain

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

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)

Study Overview

• Status: Completed
• Conditions: Influenza A H3N2
• Intervention / Treatment: Other: Influenza A H3N2 virus dose arm 1; Other: Influenza A H3N2 virus dose arm 2; Other: Influenza A H3N2 virus dose arm 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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, E14 5NR
    • hVIVO Services Ltd, 40 Bank Street

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose 3; Optional: TBD, depending on outcome of Part A	Other: Influenza A H3N2 virus dose arm 3; TBD, depending on outcome of Part A
Experimental: Dose 1; Medium dose, expected to be approximately 10^4.5 tissue culture infective dose 50% (TCID50)/mL (titer may be adjusted based on stock titer)	Other: Influenza A H3N2 virus dose arm 1; Medium dose, approximately 10^4.5 TCID50/mL
Experimental: Dose 2; High dose, expected to be approximately 10^5.5 tissue culture infective dose 50% (TCID50)/mL (titer may be adjusted based on stock titer)	Other: Influenza A H3N2 virus dose arm 2; High dose, approximately 10^5.5 TCID50/mL

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of Adverse Events Related to the Viral Challenge	Occurrence of adverse events (AEs) related to the viral challenge from viral challenge (Day 0) to the Day 28 follow-up visit.	Day 0 to Day 28
Occurrence of Serious Adverse Events Related to the Viral Challenge	Occurrence of serious adverse events (SAEs) related to the viral challenge from viral challenge (Day 0) to the Day 28 follow-up visit.	Day 0 to Day 28
Induces Laboratory-confirmed Infection in ≥40% of Inoculated Participants	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).	Day 1 to Day 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Viral Culture-confirmed Influenza Infection.	Viral culture-confirmed influenza infection, defined as a quantifiable viral culture measurement, from Day 1 pm to planned discharge from quarantine (Day 8 am).	Day 1 to Day 8
VL-AUC of Influenza Challenge Virus as Determined by qRT-PCR	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)	Day 1 to Day 8
Peak Viral Load of Influenza Challenge Virus as Determined by qRT-PCR	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).	Day 1 to Day 8
VL-AUC of Influenza Challenge Virus as Determined by Viral Culture	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)	Day 1 to Day 8
Peak Viral Load of Influenza Challenge Virus as Determined by Viral Culture	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).	Day 1 to Day 8
Area Under the Total Clinical Symptoms Score-time Curve (TSS-AUC)	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).	Day 1 to Day 8
Peak Total Symptoms Diary Card Score	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).	Day 1 to Day 8
Peak Daily Symptoms Diary Card Score	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).	Day 1 to Day 8
Laboratory-confirmed Febrile Influenza Infection	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).	Day 1 to Day 8
qRT-PCR-confirmed Influenza-like Illness (Centers for Disease and Control [CDC])	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.	Day 1 to Day 8
qRT-PCR-confirmed Influenza-like Illness (World Health Organization [WHO])	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).	Day 1 to Day 8
Laboratory-confirmed Moderately Severe Symptomatic Influenza Infection	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).	Day 1 to Day 8
Laboratory-confirmed Symptomatic Influenza Infection	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).	Day 1 to Day 8
Viral Culture Laboratory-confirmed Moderately Severe Symptomatic Influenza Infection	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).	Day 1 to Day 8

Collaborators and Investigators

• Sponsor: Hvivo
• Investigators: Principal Investigator: Alexandre Lima, MD-PhD, hVIVO Services Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2024
• Primary Completion (Actual): March 10, 2025
• Study Completion (Actual): March 10, 2025

Study Registration Dates

• First Submitted: September 23, 2024
• First Submitted That Met QC Criteria: September 23, 2024
• First Posted (Actual): September 26, 2024

Study Record Updates

• Last Update Posted (Actual): April 23, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Influenza; Flu; H3N2; Human Challenge Trial
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Influenza, Human
• Other Study ID Numbers: HRD-vCS-006

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No