DAS181 Treatment of Severe Lower Respiratory Tract Parainfluenza Virus Infection in Immunocompromised Patients: A Phase 2 Randomized, Placebo-Controlled Study

• Published in: Clinical infectious diseases Vol. 73; no. 3; pp. e773 - e781
• Main Authors: Chemaly, Roy F, Marty, Francisco M, Wolfe, Cameron R, Lawrence, Steven J, Dadwal, Sanjeet, Soave, Rosemary, Farthing, Jason, Hawley, Stephen, Montanez, Paul, Hwang, Jimmy, Ho, Jennifer, Lewis, Stanley, Wang, George, Boeckh, Michael
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 02.08.2021
• Subjects: Online Only; Lower respiratory tract infections; Parainfluenza virus; DAS181; Immunocompromised; Supplemental oxygen
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/ciab113

There are no antiviral therapies for Parainfluenza virus (PIV) infections. DAS181, a sialidase fusion protein, has demonstrated activity in in vitro and in animal models of PIV. Adult immunocompromised patients diagnosed with PIV lower respiratory tract infection (LRTI) who required oxygen supplementation were randomized 2:1 to nebulized DAS181 (4.5 mg/day) or matching placebo for up to 10 days. Randomization was stratified by need for mechanical ventilation (MV) or supplemental oxygen (SO). The primary endpoint was the proportion of patients reaching clinical stability survival (CSS) defined as returning to breathing room air (RTRA), normalization of vital signs for at least 24 hours, and survival up to day 45 from enrollment. A total of 111 patients were randomized to DAS181 (n=74) or placebo (n=37). CSS was achieved by 45.0% DAS181 treated patients in the SO stratum compared with 31.0% for placebo (p=0.15), while patients on MV had no benefit from DAS181. The proportion of patients achieving RTRA was numerically higher for SO stratum DAS181 patients (51.7%) compared with Placebo (34.5%) at Day 28 (p=0.17). In a post-hoc analysis of solid organ transplant, hematopoietic cell transplantation within one year, or chemotherapy within one year, more SO stratum patients achieved RTRA on DAS181 (51.8%) when compared to placebo (15.8%) by day 28 (p=0.012). The primary endpoint was not met, but post-hoc analysis of the RTRA component suggests DAS181 may have clinical activity in improving oxygenation in select severely immunocompromised patients with PIV LRTI who are not on mechanical ventilation.