Interleukin-1 blockade with RPH-104 in patients with acute ST-elevation myocardial infarction: study design and rationale

M Samsonov, V Bogin, B W Van Tassell, A Abbate, M Samsonov, V Bogin, B W Van Tassell, A Abbate

Abstract

Background: Myocardial injury of ST-segment elevation myocardial infarction (STEMI) initiates an intense inflammatory response that contributes to further damage and is a predictor of increased risk of death or heart failure (HF). Interleukin-1 (IL-1) is a key mediator of local and systemic inflammatory response to myocardial damage. We postulate that the use of the drug RPH-104, which selectively binds and inactivates both α and β isoforms of IL-1 will lead to a decrease in the severity of the inflammatory response which will be reflected by decrease in the concentration of hsCRP, as well as the rate of fatal outcomes, frequency of new cases of HF, changes in levels of brain natriuretic peptide (BNP) and changes in structural and functional echocardiographic parameters.

Methods: This is a double blind, randomized, placebo-controlled study in which 102 patients with STEMI will receive a single administration of RPH-104 80 mg, RPH-104 160 mg or placebo (1:1:1). The primary endpoint will be hsCRP area under curve (AUC) from day 1 until day 14. Secondary endpoints will include hsCRP AUC from day 1 until day 28, rate of fatal outcomes, hospitalizations due to HF and other cardiac and non-cardiac reasons during 12-month follow-up period, frequency of new cases of HF, changes in levels of brain natriuretic peptide (BNP, NT-pro-BNP), changes in structural and functional echocardiographic parameters during 12-month follow-up period compared to baseline. The study started in October 2020 and is anticipated to end in 2Q 2022.

Trial registration: ClinicalTrials.gov, NCT04463251. Registered on July 9, 2020.

Keywords: Cardiovascular diseases; IL-1; Inflammation; Myocardial infarction; RPH-104; STEMI; Trial design.

Conflict of interest statement

Dr. Mikhail Samsonov is the Chief Medical Officer of R-Pharm JSC, the developer of RPH-104. Dr. Vlad Bogin is the CEO of Cromos Pharma, LLC, the CRO that is conducting the study. Dr. Van Tassell has received research support from Kiniksa, Novartis, Olatec, Serpin Pharma, Swedish Orphan Biovitrum. Dr. Van Tassell has served as a paid advisor to Cromos Pharma and Serpin Pharma. Dr. Abbate has received research support from Kiniksa, Novartis, Olatec, Serpin Pharma, Swedish Orphan Biovitrum. Dr. Abbate has served as a paid advisor to Cromos Pharma, Eli Lilly, Janssen, Kiniksa, Novo-Nordisk, Olatec, Serpin Pharma.

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