Source: Annual Congress 2012 - Lung transplantation: studies in candidates and recipients

Abstract

ALN-RSV01 is a small interfering RNA targeting RSV replication. A Phase 2a randomized, controlled trial in 24 RSV-infected lung transplant patients administering nebulized ALN-RSV01 or PBO daily for 3 days was previously conducted in which ALN-RSV01 led to a significant decrease in new or progressive bronchiolitis obliterans syndrome (BOS) at Day 90 (p=0.027). We have now performed a Phase 2b multi-center, randomized, double-blind, PBO controlled trial in 87 RSV-infected lung transplant patients to examine the impact of ALN-RSV01 on the incidence of new or progressive BOS at Day 180. RSV positive subjects were randomized (1:1) to receive nebulized ALN-RSV01 or PBO daily for 5 days, alongside the institution‘s standard-of-care. Patients were prospectively stratified for: 1) days from symptom onset to treatment; and 2) pre-infection BOS grade. Of the 3,985 patients prescreened, 218 were RSV positive, of which 45 were randomized to receive ALN-RSV01 and 42 to receive PBO [intent-to-treat (ITT) population]. Ten patients were without confirmed RSV by central laboratory testing, thus a total of 77 patients (ALN-RSV01, n=44; PBO, n=33) comprised the ITTc (ITT central RSV+) population. Baseline viral load was balanced between both treatments. ALN-RSV01 was generally safe and well tolerated. There was a decrease in new or progressive BOS at Day 180 in ALN-RSV01-treated patients compared to PBO in the ITTc population (13.6% vs 30.3%, p=0.058), which was statistically significant by prospectively defined Last Observation Carried Forward (p=0.028) and Per-Protocol (p=0.025) analyses. ALN-RSV01 had a treatment effect of 54-65% in all of the pre-specified populations.

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A. Simon, V. Karsten, J. Cehelsky, S. Shah, J. Gollob, R. Meyers, A. Vaishnaw, A. Glanville, M. Zamora, J. DeVincenzo, S. Arcasoy, M. Musk, U. Sommerwerk, J. Gottlieb (Cambridge, Denver, Memphis, New York, United States Of America; Darlinghurst, Wembley, Australia; Essen, Hannover, Germany). LATE-BREAKING ABSTRACT: Results of a phase 2b multi-center trial of ALN-RSV01 in respiratory syncytial virus (RSV)-infected lung transplant patients. Eur Respir J 2012; 40: Suppl. 56, 1476

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