Rhinovirus Challenge in Asthmatics and Healthy Volunteers to Evaluate the Safety and Appropriate Dose of a GMP Human Rhinovirus 16 Preparation for Challenge Studies in Mild-Moderate Asthmatics taking ICS

Introduction: Rhinovirus (RV) infection is the most important trigger for asthma exacerbation. However, no GMP grade RV preparation and established protocols are available for human RV challenge studies. Aim: To establish safety and tolerability of a new GMP grade U-BIOPRED human RV16 (RV16UB) and to identify an appropriate dose to study biomarkers in asthmatics following RV challenge. Methods: Study 1: Single doses of 10, 100 and 1000 TCID50 of RV16UB were administered intranasally in healthy subjects (n=18) and 10 and 100 TCID50 in mild-moderate asthmatics on ICS control therapy (n=18), taking LABA and not taking LABA. Study 2: Single doses of 100 TCID50 were given to asthmatics on ICS not taking LABA (n=23) and changes from baseline in lung function, Asthma Control Diary (ACD), Common Cold Symptoms Score (CSS) and FeNO were determined (time weighted average days 1-7; TWA1-7). Results: Study 1: All doses of RV16UB were well tolerated in asthma and controls. A dose of 100 TCID50 induced cold symptoms and detectable viral RNA titers in most asthmatics. Study 2: Following challenge with 100 TCID50 morning and evening TWA1-7 FEV1 were significantly reduced by -1.7% and – 2.1% respectively. Max. FEV1 drop post challenge was 6.8%. TWA1-7 ACD and CSS were significantly increased after challenge (2.7 and 4.0 respectively). No significant changes in FeNO were found. Conclusion: A dose of 100 TCID50 of RV16UB was safe in asthmatics and induced a small, but significant reduction in FEV1 (-2%). Significant increases in ACD and CSS were found. Changes in biomarkers are under investigation.