ArticleJournal of intensive medicine2025
Safety and efficacy of selective RIPK1 inhibitor SIR1-365 in hospitalized patients with severe COVID-19: A multicenter, randomized, double-blind, phase 1b trial.
Article in Journal of intensive medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
3 citing papers in PubMed.
- Receptor-Interacting Protein Kinase 1 (RIPK1): A Potential Therapeutic Target in Ischemic Stroke.Molecular neurobiology · 2026Review
- Discovery of SARS-CoV-2 PLpro inhibitors and RIPK1 inhibitors with synergistic antiviral efficacy in a mouse COVID-19 model.Acta pharmaceutica Sinica. B · 2026Article
- RIPK1 signaling pathways: implications for autoimmune and neuroinflammatory diseases.Frontiers in immunology · 2025Review
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Receptor-interacting protein kinase 1 (RIPK1), a serine/threonine protein kinase, is mainly activated by pro-inflammatory cytokines and pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and its activation could result in apoptosis, necroptosis, or inflammation. This study was conducted to evaluate the safety and efficacy of a potent and selective inhibitor of RIPK1, SIR1-365, in hospitalized patients with severe coronavirus disease 2019 (COVID-19). Methods: This multicenter, randomized, double-blind, phase 1b study screened patients from December 18, 2020 until November 27, 2021. Adults hospitalized with severe COVID-19 (diagnosed ≤2 weeks before screening) were randomized 1:1 to receive oral placebo or SIR1-365 100 mg three times daily for ≤14 consecutive days, with standard-of-care. The primary objective was to evaluate SIR1-365 safety and tolerability. Secondary objectives included an assessment of SIR1-365 efficacy. Descriptive statistics were used to summarize safety. The study was not powered for efficacy testing. Relevant inferential statistical tests were used to aid interpretation of differences in clinical efficacy. Results: Forty-five patients were randomized, 42 were treated. Eighteen patients experienced treatment-emergent adverse events (TEAEs) and 7 patients were ≥ grade 3. Fewer SIR1-365-treated Conclusions: SIR1-365 was well tolerated and demonstrated a trend toward quicker recovery than placebo in hospitalized patients with severe COVID-19.
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