Dose, safety, and pathogenicity of a new influenza A H3N2 virus strain

• Research type

  Research Study

• Full title

  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

• IRAS ID

  341061

• Contact name

  Alexandre Lima

• Contact email

  a.lima@hvivo.com

• Sponsor organisation

  hVIVO Services Ltd.

• Duration of Study in the UK

  1 years, 5 months, 30 days

• Research summary

  Summary of Research:
  This is an exploratory study of an influenza A 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 influenza A challenge virus.

  The study will be conducted in 2 parts. In Part A, 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).

  Each participant will remain in the study for approximately 1 month from admission to quarantine to the last clinic visit.

  The study is divided into three phases:
  1) Screening phase: Screening will occur between Day -90 to Day -2/-1. Historical generic screening data collected through the hVIVO generic screening process may be transferred to this study after the study-specific consent form has been signed by the participant.
  2) Quarantine phase: Participants will stay in the quarantine unit for approximately 11 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: Final follow-up visit 28 days (±3 days) after the day they receive the virus. Their symptoms will be reassessed, and a complete safety examination performed.

  Summary of Findings:
  The main purpose of the study was to find the safest and most effective dose of a specific type of influenza virus, known as influenza A/England/7763/2022 [H3N2] (the study virus), to use in future studies. The study was divided into two parts with 33 participants;, healthy men and women aged 18 to 55, all of which were experimentally infected with the study virus and completed the study. This study was conducted by hVIVO Services Ltd.

  Part 1: 21 participants were randomly split into four groups and were assigned to one of two dose levels using pipettes or Mucosal Atomization Device® (MAD) to administer the virus:
  • Medium Dose -– 10^4.5 TCID50 /mL, pipette administration
  • Medium Dose – 10^4.5 TCID50/mL, MAD administration
  • High Dose – 10^5.5 TCID50/mL, pipette administration
  • High Dose – 10^5.5 TCID50/mL, MAD administration

  Part 2: 12 participants were included in the expansion group of the High Dose -– 10^5.5 TCID50/mL, MAD administration group

  Both parts of the study were single-blind; participants did not know the virus dose level (or relative dose level [i.e., higher or lower than other participants]) that they received. Although this was a single-blind study, the investigator staff performing subjective assessments (e.g., directed physical examinations) were also blinded to which virus dose level the participants received in Part A.

  There was a higher proportion of male participants in the medium dose pipette (80.0%), medium dose MAD (100%), and high dose MAD (78.9%) arms, though this was not expected to have impacted the study results.

  Safety:
  The study virus was generally well tolerated in participants. There were no deaths, Serious Adverse Events (SAE)s, or study discontinuation due to the study virus. All Adverse Events (AE)s were of mild or moderate severity, and all resolved by the end of the study. No trends were identified in the incidence of AEs.

  Overall, 15 participants (45.5%) had a total of 24 AEs, 7 of which were determined by the investigator to be related to the study virus and were all in the High Dose groups. These were: alanine aminotransferase increased (liver enzyme) (2 participants), C-reactive protein increased (liver enzyme) (1 participant), gamma-glutamyltransferase increased (liver enzyme) (1 participant), lymphopenia (Low blood lymphocytes) (1 participant), neutropenia (Low blood neutrophils) (1 participant), and thrombocytopenia (Low blood platelets) (1 participant).

  Conclusions:
  The incidence of laboratory-confirmed infection in the high dose MAD group was 63.2%; compared to 75.0% in the high dose pipette arm, and 60.0% in both medium dose arms.

  The researchers also looked at various health measures like blood tests, vital signs, and physical exams and found no clinically meaningful findings or patterns across the doses of the virus.

  In summary, inoculation with the study virus was safe and well tolerated at both the medium and high dose and by both pipette and MAD administration. All dose groups met the protocol-specified ideal condition of causing laboratory-confirmed infection in between 50% and 80% of participants who were given the study virus. The expanded high dose MAD group showed strong infection rates, virology, and symptoms, suitable for future studies.
  

• REC name

  Wales REC 6

• REC reference

  24/WA/0090

• Date of REC Opinion

  27 Mar 2024

• REC opinion

  Favourable Opinion