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J Heart Lung Transplant. 2016 Feb;35(2):213-21. doi: 10.1016/j.healun.2015.08.012. Epub 2015 Sep 3.

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

Author information

1
Department of Respiratory Medicine, Hannover Medical School, Biomedical Research in End stage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), Germany. Electronic address: gottlieb.jens@mh-hannover.de.
2
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado at Denver Health Sciences Center, Aurora, Colorado.
3
Center for Thoracic Transplantation at the Heart & Lung Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ.
4
Department of Respiratory Medicine, Royal Perth Hospital, Perth, Australia.
5
Department of Pneumology, Ruhrlandklinik, Westdeutsches Lungenzentrum am Universitaetsklinikum Essen GmbH, Essen, Germany.
6
Departemnt of Medicine, Loyola University Medical Center, Maywood, IL, USA.
7
Department of Medicine, New York-Presbyterian Hospital/Columbia University Medical Center, New York, NY.
8
Department of Pediatrics, University of Tennessee Center for Health Sciences, Memphis, Tennessee.
9
Alnylam Pharmaceuticals, Cambridge, Massachusetts.
10
Lung Transplant Unit, St. Vincent's Hospital, Darlinghurst, New South Wales, Australia.

Abstract

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.

KEYWORDS:

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

PMID:
26452996
DOI:
10.1016/j.healun.2015.08.012
[Indexed for MEDLINE]

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