H1N1v Virus Challenge Study in Healthy Subjects
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a study of a reverse-engineered, Good Manufacturing Practice (GMP) grade,
      antiviral-sensitive, influenza A/Bethesda/MM2/H1N1 virus (A/California/04/2009/H1N1-like)
      infection to assess the effect of pre-existing immunity on clinical and immunological
      responses. Up to 80 healthy adult subjects will undergo intranasal inoculation with
      A/Bethesda/MM2/H1N1 virus, and their clinical manifestations, viral shedding and
      immunological responses will be characterized. The Primary Objective for this study is to
      evaluate the association of symptomatic Reverse Transcription-Polymerase Chain Reaction
      (RT-PCR)-positive influenza virus infection post-challenge and pre-existing Hemagglutinin
      Inhibition Test (HAI) antibody titers.
    

Detailed description: 
      This is a study of a reverse-engineered, Good Manufacturing Practice (GMP) grade,
      antiviral-sensitive, influenza A/Bethesda/MM2/H1N1 virus (A/California/04/2009/H1N1-like)
      infection to assess the effect of pre-existing immunity on clinical and immunological
      responses. Up to 80 healthy adult subjects will undergo intranasal inoculation with
      A/Bethesda/MM2/H1N1 virus, and their clinical manifestations, viral shedding and
      immunological responses will be characterized. This proposed study will establish a H1N1
      influenza virus controlled human infection (CHI) model at the National Institute of Allergy
      and Infectious Diseases (NIAID) Division of Microbiology and Infectious Diseases
      (DMID)-sponsored Vaccine and Treatment Evaluation Units (VTEU) clinical study sites. The
      model has been developed and used by NIAID Division of Intramural Research. The proposed
      study will expand US research capacity to perform influenza CHI studies to advance the
      understanding of influenza pathogenesis and novel vaccine research and development. The
      Primary Objective for this study is to evaluate the association of symptomatic Reverse
      Transcription-Polymerase Chain Reaction (RT-PCR)-positive influenza virus infection
      post-challenge and pre-existing Hemagglutinin Inhibition Test (HAI) antibody titers. The
      Secondary Objectives for this study are: 1) To describe viral recovery by quantitative RT-PCR
      from study subjects at baseline and post-challenge; 2) To describe serum HAI and MN antibody
      responses post-challenge in healthy subjects by infection status; 3) To evaluate the
      association of asymptomatic RT-PCR-positive influenza virus infection (viral shedding)
      post-challenge and pre-existing HAI antibody titers; 4) To evaluate the association of
      symptomatic RT-PCR-negative status post-challenge and pre-existing HAI antibody titers; 5) To
      determine the frequency of serious adverse events (SAE) post-challenge.
    

Intervention name(s): Influenza A/Bethesda/MM2/H1N1 Challenge
Intervention type(s): Biological
Intervention description(s): Reverse-genetics derived live A/California/04/2009/H1N1-like influenza virus passaged six times in Vero cells.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: A/Bethesda/MM2/H1N1 Virus; Challenge; Dose Escalation; Healthy Subjects; Influenza; Live virus