Biology Reference
In-Depth Information
Table 15.1
Day 90 clinical outcomes (intent-to-treat population)
Day 90 outcome
ALN-RSV01
N
= 16
Placebo
N
= 8
p
-Value
Survival
16 (100)
8 (100)
NS
Intubation
0
0
NS
Acute rejection
2 (12.5)
1 (12.5)
NS
Respiratory Infections after day 30
4 (25)
1 (12.5)
0.62
Change in BOS from baseline
New onset
0
3 (37.5)
0.027
Progressive
1 (6.3)
1 (12.5)
1.00
Total new onset or progressive
1 (6.3)
4 (50)
0.027
Data presented as
n
(%)
p
-Value are for Fisher exact test for mean score
Adapted from Zamora et al. [
36
]
BOS
bronchiolitis obliterans syndrome,
NS
not signi fi cant
centers throughout the world. In this study, the primary end point was the effect of
ALN-RSV01 on the incidence of new or progressive BOS at day 180. Secondary
end points include the impact of ALN-RSV01 on BOS assessment at day 90, symp-
tom scores, antiviral parameters, and safety. RSV-positive subjects were random-
ized 1:1 to receive either nebulized ALN-RSV01 (0.6 mg/kg) or placebo daily for
5 days, in addition to the hospital's standard-of-care. During randomization, sub-
jects were stratified to the treatment arms based on two binary factors (1) time from
symptom onset to treatment start and (2) preinfection BOS grade. Stratifying by
onset from diagnosis to treatment start was implemented to try to ensure similar
baseline viral load in the treatment groups.
Of the 3,985 subjects prescreened with respiratory symptoms at 33 centers, 218
were RSV positive (5.5% of the total), of which 87 were randomized into the study.
BOS scores at days 90 and 180 were adjudicated by an independent committee
made up of physicians who were lung transplant specialists not participating in the
trial and who were blinded to study drug treatment assignment. In addition, RSV
samples (oropharyngeal wash and nasal swabs) were analyzed by PCR at a central
laboratory, and all results were reviewed by a quality oversight committee com-
prised of physicians who were infectious disease specialists not participating in the
trial. Enrollment for this study was completed (October 2011), and subjects are now
in the follow-up phase through the first half of the year. Results from this trial are
expected to be reported in 2012.
15.4
Future Perspectives for RNAi in the Clinic
The unmet need for safe and effective therapies remains high as RSV-induced lower
respiratory infection results in hospitalization in up to 10% of children (<5 year old)
and in 16% of elderly patients [
1,
2
]. While a large number of anti-RSV therapeutics
have been studied, such as antisense oligonucleotides, small molecule inhibitors,
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