Clinical trial NCT01769573
Conditions: Healthy Volunteers
Keywords: normal
Sponsor: University of Wisconsin, Madison
Start date: 2013-07-01; Completion date: 2017-12-01
Enrollment: 36 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief 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.

Arms: arm 1: RG-HRV16 dose of 100 TCID50 administered intranasally (0.25ml per nostril) one time. arm 2: RG-HRV16 dose of 1,000 TCID50 administered intranasally (0.25ml per nostril) one time. arm 3: RG-HRV16 dose of 10,000 TCID50 administered intranasally (0.25ml per nostril) one time. arm 4: Diluent administered intranasally (0.25ml per nostril) one time. arm 5: RG-HRV16 dose of 500 TCID50 administered intranasally (0.25ml per nostril) one time.
Interventions: intervention 1: RG-HRV16 intervention 2: Placebo
Intervention descriptions: intervention 1: A suspension of the RG-HRV16 virus in Minimal Essential Media (MEM, HyClone) containing 0.1% Human Serum Albumin intervention 2: 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.

Protocol documents: