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@article{Nissen:2022:10.1001/jama.2022.5050,
author = {Nissen, SE and Wolski, K and Balog, C and Swerdlow, D and Scrimgeour, AC and Rambaran, C and Wilson, RJ and Boyce, M and Ray, KK and Cho, L and Watts, GF and Koren, M and Turner, T and Stroes, ES and Melgaard, C and Campion, G},
doi = {10.1001/jama.2022.5050},
journal = {JAMA: Journal of the American Medical Association},
pages = {1679--1687},
title = {Single ascending dose study of a short interfering RNA targeting lipoprotein(a) production in individuals with elevated plasma lipoprotein(a) levels},
url = {http://dx.doi.org/10.1001/jama.2022.5050},
volume = {327},
year = {2022}
}

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TY  - JOUR
AB  - Importance  Lipoprotein(a) (Lp[a]) is an important risk factor for atherothrombotic cardiovascular disease and aortic stenosis, for which there are no treatments approved by regulatory authorities.Objectives  To assess adverse events and tolerability of a short interfering RNA (siRNA) designed to reduce hepatic production of apolipoprotein(a) and to assess associated changes in plasma concentrations of Lp(a) at different doses.Design, Setting, and Participants  A single ascending dose study of SLN360, an siRNA targeting apolipoprotein(a) synthesis conducted at 5 clinical research unit sites located in the US, United Kingdom, and Australia. The study enrolled adults with Lp(a) plasma concentrations of 150 nmol/L or greater at screening and no known clinically overt cardiovascular disease. Participants were enrolled between November 18, 2020, and July 21, 2021, with last follow-up on December 29, 2021.Interventions  Participants were randomized to receive placebo (n = 8) or single doses of SLN360 at 30 mg (n = 6), 100 mg (n = 6), 300 mg (n = 6), or 600 mg (n = 6), administered subcutaneously.Main Outcomes and Measures  The primary outcome was evaluation of safety and tolerability. Secondary outcomes included change in plasma concentrations of Lp(a) to a maximum follow-up of 150 days.Results  Among 32 participants who were randomized and received the study intervention (mean age, 50 [SD, 13.5] years; 17 women [53%]), 32 (100%) completed the trial. One participant experienced 2 serious adverse event episodes: admission to the hospital for headache following SARS-CoV-2 vaccination and later for complications of cholecystitis, both of which were judged to be unrelated to study drug. Median baseline Lp(a) concentrations were as follows: placebo, 238 (IQR, 203-308) nmol/L; 30-mg SLN360, 171 (IQR, 142-219) nmol/L; 100-mg SLN360, 217 (IQR, 202-274) nmol/L; 300-mg SLN360, 285 (IQR, 195-338) nmol/L; and 600-m
AU  - Nissen,SE
AU  - Wolski,K
AU  - Balog,C
AU  - Swerdlow,D
AU  - Scrimgeour,AC
AU  - Rambaran,C
AU  - Wilson,RJ
AU  - Boyce,M
AU  - Ray,KK
AU  - Cho,L
AU  - Watts,GF
AU  - Koren,M
AU  - Turner,T
AU  - Stroes,ES
AU  - Melgaard,C
AU  - Campion,G
DO  - 10.1001/jama.2022.5050
EP  - 1687
PY  - 2022///
SN  - 0098-7484
SP  - 1679
TI  - Single ascending dose study of a short interfering RNA targeting lipoprotein(a) production in individuals with elevated plasma lipoprotein(a) levels
T2  - JAMA: Journal of the American Medical Association
UR  - http://dx.doi.org/10.1001/jama.2022.5050
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000793675300017&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://jamanetwork.com/journals/jama/fullarticle/2790912
VL  - 327
ER  -

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