A Phase 2b, Randomized, Double-blind, Placebo-Controlled Multicenter Study Evaluating Antiviral Effects, Pharmacokinetics, Safety, and Tolerability of Presatovir in Hematopoietic Cell Transplant Recipients with Respiratory Syncytial Virus (RSV) Infection of the Lower Respiratory Tract

Marty, Francisco M; Chemaly, Roy F; Mullane, Kathleen M; Lee, Dong-Gun; Hirsch, Hans H; Small, Catherine B; Bergeron, Anne; Shoham, Shmuel; Ljungman, Per; Waghmare, Alpana; Blanchard, Elodie; Kim, Yae-Jean; McKevitt, Matt; Porter, Danielle P; Jordan, Robert; Guo, Ying; German, Polina; Boeckh, Michael; Watkins, Timothy R; Chien, Jason W; Dadwal, Sanjeet S

Abbreviations: CMV, cytomegalovirus; GVHD, graft-vs-host disease; HCT, hematopoietic cell transplant; LRT, lower respiratory tract; max, maximum; min, minimum; RSV, respiratory syncytial virus. a On the day of the first dose of study drug, 11 patients receiving presatovir and 10 patients receiving placebo were being treated with ribavirin. Current or intended use of ribavirin on day of randomization was used to stratify randomization. b These patients were excluded from the efficacy population. c For these values, n = 29 for the presatovir arm and n = 28 for the placebo arm. [27] . However, no polymerase inhibitor has demonstrated clinical efficacy in a natural infection setting to date. Furthermore, nasal viral load is questionable as a primary endpoint for proofof-concept studies in naturally infected patients with LRTI because upper respiratory tract samples, although more convenient to obtain, may not reflect viral activity in the lower respiratory tract, particularly in immunocompromised patients. Alternative approaches are needed for noninvasive measurement of viral disease dynamics and antiviral activity in lower airway and alveolar tissue.