C93-04 Treatment With Vapendavir After Rhinovirus Challenge in COPD Protects Lung Function and Accelerates Virus Clearance and Symptom Resolution - Results From a Phase 2A Randomised Double-Blind Placebo-Controlled Trial

Abstract Rationale Acute exacerbations (AECOPD) are the primary contributor to COPD-associated morbidity and mortality and are associated with accelerated lung function decline and impaired quality of life (QoL). Approximately 50% of AECOPD are caused by rhinovirus (RV) infection, for which there is no vaccine or treatment. We examined the efficacy of Vapendavir (VPV), an oral potent and specific RV capsid inhibitor, in experimental RV-A16 infection of COPD patients. Methods 52 participants with GOLD stage II COPD were enrolled, 44 were inoculated intranasally with RV-A16, and 40 developed symptoms and were randomized. Upon reporting a cold or an increase of ≥ 2 points above baseline upper or lower respiratory symptom scores (URSS/LRSS), participants were dosed orally with placebo (n = 20) or VPV (n = 20) for 7 days. Participants were followed up for 42 days post-infection. Outputs included participant reported symptom scores, QoL, pulmonary function tests and virus load. Results Vapendavir treatment was well tolerated with no evident safety concerns. VPV reduced RV-induced worsening of QoL assessed by the St George’s Respiratory Questionnaire (SGRQ) (VPV median -5.52 95%CI -11.47-0.420, placebo 4.12 -2.05-10.29, p=0.04) and responder analysis of numbers of participants with clinically significant (≥4 point) worsenings was fewer with VPV n = 5 25% vs. placebo 11 58%, p=0.036. SGRQ domains including symptoms (difference in favor of VPV=-6.39), activity (-10.44), and impact (-11.70) all favoured VPV. Symptoms measured by EXACT-RS area under the curve AUC were significantly improved in patients treated with VPV (p = 0.018). ER-S domains including breathlessness (AUCDay21 -12.66), cough/sputum (AUCDay21 -16.56), and chest symptoms (AUCDay21 -11.53) all favored VPV. Spirometry was not significantly different between groups. Oscillometry however revealed improved ventilation inhomogeneity in VPV-treated participants (AUC AX VPV -163.99 -434.25-106.27, placebo 287.69 32.92-542.47, p=0.018) and a trend towards reduced worsening in small airways function (AUC R5-R20 VPV -1.87 -11.39-7.65, placebo 8.71 -0.25-17.67, p = 0.11). VPV significantly reduced RV-A16 peak and AUC virus load in nasal swabs vs placebo (peak -1.3 Log10 copies/mL, p=0.03, AUC -25 Log10 copies/mL*days, p=0.04) with a trend (p=0.074) towards reduced peak virus load in nasal lavage samples. VPV reduced the duration of virus shedding in nasal swabs (VPV 5 days, placebo 11 days, p = 0.04). Conclusions Vapendavir reduced upper and lower respiratory symptoms and accelerated virus clearance and symptom resolution following experimental RV-A16 infection in individuals with COPD, supporting its progression into further clinical trials in patients with COPD and other chronic lung diseases. This abstract is funded by: Altesa BioSciences Inc