A First-in-Human Safety and Dose-Finding Study of New Type-16 Human Rhinovirus (RG-HRV16) Inoculum in Healthy Volunteers
Condition: Healthy Volunteers
Study type: Interventional
Phase: Phase 1

Summary: 
      This research study will test different doses of RG-HRV16 to find the minimum dose needed to
      give research subjects cold symptoms of at least moderate intensity. The study will also test
      the safety of RG-HRV16. This information will be used in future studies (for example, to test
      antiviral preparations, sprays that could protect from getting a cold or decrease cold
      symptoms or to understand more about how rhinovirus can lead to asthma worsening). RG-HRV16
      is a common cold virus that has been made in a new way and has not been used in humans
      before.
    

Detailed description: 
      Rhinoviruses are the most frequently cause of the common cold. HRV16 (Family Picornaviridae
      Genus Rhinovirus type 16) has been used extensively to induce colds in studies of
      experimentally inoculated volunteers that are designed to study the pathogenesis of colds and
      effects of antiviral medications.

      Experimental inoculation with human rhinovirus type 16 (HRV16) administered intranasally via
      aerosolization has been used at the University of Wisconsin for over 30 years, and has proven
      to be a safe tool to reproducibly induce symptomatic colds. HRV has been linked with
      exacerbations of asthma and COPD, and this model has been used to evaluate inflammatory
      mechanisms and to test the efficacy of treatments for the common cold. Recent refinements in
      the technology available to produce and safety test reagents that are intended to be
      administered to human volunteers as part of research protocols has prompted us to produce a
      new lot of HRV16 in accordance with standards of current Good Manufacturing Procedures
      (cGMP). For this inoculum, we have used a cDNA clone (reverse genetics) to generate source
      virus, thus this new virus inoculum will be referred to as RG-HRV16.

      This approach has two main advantages over using viruses isolated from nasal secretions.
      First, several "new" respiratory viruses (e.g. metapneumovirus, bocavirus, SARS, rhinovirus
      group C) have been discovered in the past 10 years, and there is little doubt that additional
      viruses will be discovered. Therefore, it is impossible to ensure that nasal secretions that
      are chosen for isolation of "seed virus" contain only the pathogen of interest. This problem
      is minimized through the use of virus derived from a cDNA clone that was produced in E. coli.
      Second, RNA viruses, such as HRV, mutate as the virus grows because their RNA polymerases
      have no error-correcting function. The cDNA clone, reproduced by the much more accurate E.
      coli DNA polymerase, provides a stable source of virus sequence for production of future
      inocula.

      This study represents a first-in-human, phase 1 study to assess the safety of RG-HRV16 in
      humans and identify the dose needed to produce moderate-to-severe colds in 75% of
      HRV16-seronegative human volunteers.
    

Intervention name(s): RG-HRV16; Placebo
Intervention type(s): Biological; Drug
Intervention description(s): A suspension of the RG-HRV16 virus in Minimal Essential Media (MEM, HyClone) containing 0.1% Human Serum Albumin; The placebo to be used will be Minimal Essential Media (MEM, HyClone) containing 0.1% Human Serum Albumin. Placebo will be supplied in 2 ml borosilicate glass vials sealed with butyl stoppers containing 0.5 ml.
Other intervention name(s): Rhinovirus type 16
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: Single (Participant)
Primary purpose: Other
Keywords: normal