ALN-RSV01 for prevention of bronchiolitis obliterans syndrome after respiratory syncytial virus. infection in lung transplant recipients

作者：Gottlieb Jens^*; Zamora Martin R; Hodges Tony; Musk A W; Sommerwerk Urte; Dilling Daniel; Arcasoy Selim; DeVincenzo John; Karsten Verena; Shah Shaily; Bettencourt Brian R; Cehelsky Jeffrey; Nochur Sara; Gollob Jared; Vaishnaw Akshay; Simon Amy R; Glanville Allan R

来源：Journal of Heart and Lung Transplantation, 2016, 35(2): 213-221.

DOI：10.1016/j.healun.2015.08.012

• bronchiolitis obliterans
• lung transplantation
• respiratory syncytial virus
• community-acquired infections
• RNA interference
• ribavirin

BACKGROUND: Respiratory syncytial virus (RSV) infection in lung transplant (LTx) patients is associated with an increased incidence of bronchiolitis obliterans syndrome (BOS). ALN-RSV01 is a small interfering RNA targeting RSV replication that was shown in an earlier Phase 2a trial to be safe and to reduce the incidence of BOS when compared with placebo.
METHODS: We performed a Phase 2b randomized, double-blind, placebo-controlled trial in RSV-infected LTx patients to examine the impact of ALN-RSV01 on the incidence of new or progressive BOS. Subjects were randomized (1:1) to receive aerosolized ALN-RSV01 or placebo daily for 5 days.
RESULTS: Of 3,985 symptomatic patients screened, 218 were RSV-positive locally, of whom 87 were randomized to receive ALN-RSV01 or placebo (modified intention-to-treat [mITT] cohort). RSV infection was confirmed by central laboratory in 77 patients (ALN-RSV01, n = 44; placebo, n = 33), which comprised the primary analysis cohort (central mITT [mITTc]). ALN-RSV01 was found to be safe and well-tolerated. At Day 180, in ALN-RSV01-treated patients, compared with placebo, in the mITTc cohort there was a trend toward a decrease in new or progressive BOS (13.6% vs 30.3%, p = 0.058), which was significant in the per-protocol cohort (p = 0.025). Treatment effect was enhanced when ALN-RSV01 was started <5 days from symptom onset, and was observed even without ribavirin treatment. There was no significant impact on viral parameters or symptom scores.
CONCLUSIONS: These results confirm findings of the earlier Phase 2a trial and provide further support that ALN-RSV01 reduces the risk of BOS after RSV in LTx recipients.

• 出版日期2016-2