Influenza Challenge Study to Determine the Optimal Infection Dose and Safety of a Recombinant H3N2 (A/Texas/71/2017 (H3N2, Clade 3C3a) Influenza Strain
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Influenza RG-A/Texas/71/2017 (H3N2) Challenge; Placebo
Intervention type(s): Biological; Other
Intervention description(s): 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.; Sucrose phosphate glutamate (SPG) inoculum
Allocation: Randomized
Intervention model: Sequential Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Other
Keywords: A/Texas/71/2017; Influenza; Influenza Challenge Study; Recombinant H3N2; Recombinant H3N2 Influenza Strain; Safety