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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
SINGLE
Enrollment
36
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.
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States
Number of Participants With Colds With at Least Moderate Intensity
The percentage of colds of at least moderate intensity examined by RG-HRV16 dose; this will be measured by the number of subjects per RG-HRV16 dose group who have maximum weekly cold symptom score of ≥7 out of 39 on the modified Jackson criteria during the first week after inoculation
Time frame: 1 week
Frequency of Adverse Events
Safety as determined by the frequency of adverse event reporting examined by RG-HRV16 dose.
Time frame: 4 weeks
Mean Cold Symptom Score
The Mean Cold Symptom Score induced by each RG-HRV16 dose and by the placebo inoculation. The scale is called the Jackson Criteria for Cold Symptom Assessment. There are 13 variables of cold symptoms that each participant scores 0 (not present), 1 (mild), 2 (moderate) to 3 (severe), twice per day, once at 8am and once at 8pm. The 13 variables are: cough, nasal discharge, sneezing, stuffy nose, sore throat, headache, malaise, chilliness, shaking chills, fever, laryngitis, aching joints or muscles, and watery/burning eyes. The scores are added up for each time point, with a minimum score of 0 and a max score of 39 per time point. The highest score per day is taken and the highest score over the 7 day period starting from the day of the inoculation and for 7 days is deemed the mean cold symptom score. The higher the score, the more cold symptoms the participant reports and the worse the participant feels.
Time frame: 4 weeks
Infection Rate
Infection rate per RG-HRV16 dose as measured by the percentage of individuals in the dosing group with detectable viral shedding.
Time frame: 4 weeks
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